Methylenedioxyamphetamines by Asch

Query Query

Results

Date

408 reactions in Reaxys

2017-11-11 02h:46m:43s (EST)

1. Query

N H

Search as: Product, As drawn

1/129

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H N

O N H

Rx-ID: 9000069 View in Reaxys 1/408 Yield

Conditions & References

95 %

With caesium carbonate in N,N-dimethyl-formamide, Time= 2h Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys

95 %

4.1.12. (R)-Ethyl 1-(benzo[d][1,3]dioxol-5-yl)propan-2-ylcarbamate, (R)-9a General procedure: To a solution of (R)-8a (668 mg, 2.79 mmol) and CsCO3 (2.95 g,8.37 mmol, 3 equiv) in DMF (20 mL) was added BrCH2Cl (0.3 mL,4.47 mmol, 1.6 equiv) and the mixture was stirred for 2 h at room temperature. The solution was filtered through celite and evaporated.The residue was then dissolved in ethyl acetate (200 mL) and washed with water (2x25 mL) and brine (25 mL). The organic layer was dried (MgSO4) filtered and the solvent was evaporated to afford (R)-9a (0.69 g, 89percent yield) as a white solid. With caesium carbonate in N,N-dimethyl-formamide, Time= 2h, T= 20 °C Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H 2N O

N H

Rx-ID: 1835346 View in Reaxys 2/408 Yield

Conditions & References

78 %

Stage 1: in ethanol, water, Time= 1h, T= 20 °C Stage 2: With hydrogen, platinum(IV) oxide in ethanol, water, Time= 3.5h, p= 2896.11Torr , Further stages. Buchanan, Hilary A. S.; Daeid, Niamh Nic; Meier-Augenstein, Wolfram; Kemp, Helen F.; Kerr, William J.; Middleditch, Michael; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3350 - 3356 View in Reaxys

74 %

With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys With sodium cyanoborohydride in methanol Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354 View in Reaxys

H N

O O

N H

Rx-ID: 37966353 View in Reaxys 3/408 Yield 89 %

Conditions & References 4.1.12. (R)-Ethyl 1-(benzo[d][1,3]dioxol-5-yl)propan-2-ylcarbamate, (R)-9a To a solution of (R)-8a (668 mg, 2.79 mmol) and CsCO3 (2.95 g,8.37 mmol, 3 equiv) in DMF (20 mL) was added BrCH2Cl (0.3 mL,4.47 mmol, 1.6 equiv) and the mixture was stirred for 2 h at room temperature. The solution was filtered through celite and evaporated.The residue was then dissolved in ethyl acetate (200 mL) and washed with

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water (2x25 mL) and brine (25 mL). The organic layer was dried (MgSO4) filtered and the solvent was evaporated to afford (R)-9a (0.69 g, 89percent yield) as a white solid. With caesium carbonate in N,N-dimethyl-formamide, Time= 2h, T= 20 °C Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

O 13 C O

13C

H C

C H

O 13 C

13CH

NH 2

13C

H C

C H

13C

HCl

Rx-ID: 38014751 View in Reaxys 4/408 Yield

Conditions & References

86 %

Stage 1:Time= 2h, T= 100 °C , Autoclave Stage 2: With lithium aluminium tetrahydride in diethyl ether, Time= 5h, Reflux Stage 3: With hydrogenchloride in diethyl ether, isopropyl alcohol, T= 10 °C , pH= 4 Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

86 %

4 : The Synthesis of DE-[’3C5] -3,4-Methylenedioxy-N- methylamphetamine (DE-[’3C5]-MDMA) D,E-[’3C5]-MDA as a free base (100 mg, 0.54 mmol) wasdissolved in ethylformate (10 mE) and heated under pressurein an ACE pressure reactor for 2 hours at 100° C. Thereaction was cooled down and the solvent was evaporatedunder reduced pressure. The carbamate derivative was dis15 solved in dry diethyl ether (5 mE) and added dropwise to asuspension of EiA1H4 (30.75 mg, 0.81 mmol) in diethylether (10 mE). The reaction mixture was refluxed for 5 hoursand then water was added carefully after the temperaturewas cooled down to 0° C. on an ice bath. The lithium saltwas filtered through celite in a Buchner funnel and thegranules were washed thoroughly by excess ethet The etherphases was combined and washed with 5percent NaOH and brinebefore drying over MgSO4. The solvent was evaporated toyield the methamphetamine as a free base (96 mg). Thecrude product was redissolved in diethyl ether and cooleddown to 10° C. before HC1 dissolved in isopropanol (1.85M) was added in small portions until the pH was 4. The saltwas filtered off with a Buchner funnel, washed with etherand dried to yield D,E-[’3C05]-MDMA hydrochloride (110mg, 86percent based on D,E-[’3C5]-MDA) with a purity higherthan 99percent as TFAA derivative by GC/MS. Stage 1:, Time= 2h, T= 100 °C Stage 2: With lithium aluminium tetrahydride in diethyl ether, Time= 5h, Reflux Stage 3: With hydrogenchloride in diethyl ether, isopropyl alcohol, T= 10 °C , pH= 4 Patent; CHIRON AS; Johansen, Jon Eigill; Liu, Huiling; Karlsen, Morten; (15 pag.); US9435816; (2016); (B2) English View in Reaxys

O O

NH 2

O O

2H 2H

N H

Rx-ID: 10841268 View in Reaxys 5/408 Yield 53 %

Conditions & References 2; 9 :[00232] A solution of ethyl chloroformate (12.8 mL, 135 mmol) in anhydrous dichloromethane (100 mL) was slowly added to a solution of d2-l-(3,4- Methylenedioxyphenyl)-2-aminopropane (20.2 g, 1 11 mmol), anhydrous dichloromethane (250 mL), triethylamine (100 mL, 718 mmol) and 4-dimethylaminopyridine (4.7 g, 42 mmol) at 4°C. The reaction was warmed at ambient temperature and stirred for 16 hours. The residue was diluted with dichloromethane (60 mL) and washed with water (100 mL), IN hydrochloric acid (200 mL) and brine (200 mL), dried over anhydrous sodium sulfate, and evaporated to dryness. The crude product was purified by column chromatography to give the title compound (15 g, 53percent yield) as a light yellow oil. LC-MS: m/z=254 (M+H) + , 276 (M+Na)+. With triethylamine, 4-(N,N-dimethlyamino)pyridine in dichloromethane, Time= 16h, T= 4 - 20 °C Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English

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View in Reaxys O O Cl

H 2N

N H

Rx-ID: 23493313 View in Reaxys 6/408 Yield 95 %

Conditions & References 4A :To a stirred solution of MDA (4) (19 mg, 0.0881 mmol) in THF (10 mL) was added diisopropylethylamine (120 ; j. L, 0.689 mmol). The reaction was stirred at room temperature for 60 minutes. Bromoacetic acid N-hydroxy succinimide (62.5 mg, 0.2637 mmol) was added to the reaction mixture under argon. The reaction mixture was stirred at room temperature for 1 hour. Water (10 mL) was added and most of the THF was removed by rotary evaporation. The aqueous phase was extracted with CH2CI2 (3 x 30 ml). The combined organic phases were washed with water (10 mL) and dried over MgS04. The organic phase was filtered and evaporated to dryness by rotary evaporation. The residue was purified by flash column chromatography (silica gel) using ethyl acetate/hexane (2/3) as an eluent to give the desired product (18) (25 mg, 95 percent yield) ; FAB-MS: MH+ (300) ; 1H-NMR (CDCl3, 400 MHz) 8 : 6.67 (m, 3H), 6.30 (m, 1H), 5.92 (s, 2H), 4.15 (m, 1H), 3.81 (s, 2H), 2.73 (m, 1H), 2.66 (m, 1H), 1.13 (d, J=6.6Hz, 3H). With N-ethyl-N,N-diisopropylamine in tetrahydrofuran, Time= 2h, T= 20 °C Patent; DADE BEHRING INC.; WO2005/58864; (2005); (A1) English View in Reaxys O O

H 2N

S O

N O

N H

Rx-ID: 23495869 View in Reaxys 7/408 Yield 96 %

Conditions & References Preparation of compound (40) To a stirred solution of MDA (100 mg, 0.4636 mmol) in THF (15 mL) was added diisopropylethylamine (0.5 ml, 2.87 mmol). The reaction was stirred at room temperature for 30 minutes. 2-Mercapto [Sacetyl] acetic acid N-hydroxysuccinimide ester (116 mg, 0.5016 mmol) was added to the reaction mixture under nitrogen. The reaction mixture was stirred at room temperature for 2 hours. TLC analysis of the mixture showed that a less polar spot as a product in comparison with MDA. The organic solvent was removed to dryness by rotary evaporation. The residue was purified by flash column chromatography (silica gel) using ethyl acetate/hexane (1/1) as an eluent to give the desired product (40) (132 mg, 96percent yield). 1H-NMR (CDCI3, 400 MHz) 8 : 6.72 (d, J = 7.8 Hz, 1H), 6.64 (s, 2H), 6.60 (s, J = 7.8 Hz, 1H), 6.10 (m, 1H), 5.93 (s, 2H), 4.15 (m, 1H), 3.52 (d, j = 14.6 Hz, 1H), 3.42 (d, J = 14.6 Hz, 1H), 2.66 (m, 2H), 2.39 (s, 3H), 1.10 (d, J=6.7 Hz, 3H). 13C-NMR (CDCI3, 100 MHz) 8 : 196.4, 167.8, 147.9, 146.5, 131.8, 122.8, 110.2, 108.5, 101.3, 47.00, 42.3, 33.5, 30.6, 20. 2. With N-ethyl-N,N-diisopropylamine in tetrahydrofuran, Time= 2h, T= 20 °C Patent; DADE BEHRING INC.; WO2005/61482; (2005); (A1) English View in Reaxys

O O

H N

O O

N H

Rx-ID: 37966355 View in Reaxys 8/408 Yield 85 %

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less oil. This compound was then dissolved in anhydrous diethyl ether (4 mL) and 2 M HCl in diethyl ether was added dropwise, yielding the corresponding hydrochloride HCl (R)-10a as a white solid. With lithium aluminium tetrahydride in tetrahydrofuran, Time= 4h, Reflux Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

O 13 C O

13C

H C

13C

O 13 C

13C

H C

C H

NH 2

13C

HCl

Rx-ID: 44430041 View in Reaxys 9/408 Yield 75 %

Conditions & References 3.5 : 3.5 The Synthesis of DE-[’3C5]-3,4-Methylenedi-oxyamphetamine Hydrochloride (DE-[ 13C6]-MDAhydrochloride) 2-Nitro-1 -propen- 1 -yl)-3,4-methylenedioxy-[’3C5]-benzene (1.02 g, 4.8 mmol) was dissolved in 20 ml dry toluene(20 mE) and added dropwise to a mixture of Vitride (70percent in toluene, 5 mE)) and dry toluene (22.5 mE) at 70° C. After all of the nitrostyrene was added, the solution was stirred under inert atmosphere for 2 hours. The reaction was lefi overnight at room temperature for completion. 5percent NaOH inwater (50 mE) was then added carefully, and the toluene layer was separated. The water phase was washed with toluene (2x25 mE), and the organic phases were combined and washed with saturated NaHCO3 and brine and dried with anhydrous Mg504. The solvent was evaporated to yieldthe free base as a light yellow oil (930 mg). This oil was distilled on a Kugelrohr apparatus and dissolved in anhydrous diethyl ether (20 mE). The hydrochloride salt was formed by slow addition of a HC1 saturated solution in diethyl ether until pH 5. The salt was filtered from the solvent with a dry Buchner funnel and the product was washed by adding chilled diethyl ether (2x10 mE). The product was dried under reduced pressure to yield the product (800 mg, 75percent) with a purity greater than 99percent by TFAA derivatization on GC/MS. Stage 1: With sodium bis(2-methoxyethoxy)aluminium dihydride in toluene, T= 20 - 70 °C , Inert atmosphere Stage 2: With hydrogenchloride in diethyl ether, pH= 5 Patent; CHIRON AS; Johansen, Jon Eigill; Liu, Huiling; Karlsen, Morten; (15 pag.); US9435816; (2016); (B2) English View in Reaxys

O O

H N O

N H

O NH

O N H

H N

NH 2

Rx-ID: 23506693 View in Reaxys 10/408 Yield 68 %

Conditions & References Preparation of MDA-AA-14-NH2 (48); To a solution of 47 (230 mg, 0.4516 mmol) in CH2CI2 (2 ml) was added TFA (0.5 ml). The reaction mixture was stirred at room temperature for 1. 5 hours. TLC analysis of the reaction showed that the starting material (47) disappeared and a new more polar spot was displayed (silica gel, MeOH/CH2CI2 = 1/9). Most of CH2CI2 and TFA were removed by rotary evaporation under reduced pressure. The residue was further dried under high vacuum for 18 hours to remove trace of TFA. The residue was dissolved in MeOH (5 ml) and NH40H was added to adjust the pH value to 10. The MeOH and the excess of NH40H were evaporated under reduced pressure. The residue was purified by flash column chromatography using CH2CI2/MeOH (8/2) as an eluent to give the desired product (48) (126 mg, 68percent yield). 1H-NMR (CD30D, 400 MHz) 5 : 6.61 (m, 2H), 6.54 (m, 1H), 5.78 (s, 2H), 3.96 (m, 1H), 3.62-3. 53 (m, 6H), 3.45 (m, 2H), 3.28 (m, 2H), 3.01 (m, 2H), 2.58 (m, 1H), 2.49 (m, 1H), 2.37 (m, 4H), 0.99 (d, J=6.6 Hz, 3H). With trifluoroacetic acid in dichloromethane, Time= 1.5h, T= 20 °C Patent; DADE BEHRING INC.; WO2005/61482; (2005); (A1) English View in Reaxys

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N H

H 2N

S O

Rx-ID: 28999435 View in Reaxys 11/408 Yield

Conditions & References

80 %

4B :To a stirred solution of MDA (4) (10 mg, 0.04636 mmol) in THF (5 mL) was added NaH (5 mg, 0.198 mmol). The reaction was stirred at room temperature for 15 minutes. 1, 3-Dibromo-2- (methylsulfonyl) propane (14 mg, 0.05 mmol) was added to the reaction mixture at-20 °C. The reaction mixture was stirred at-20 °C for 120 minutes. Water (0.1 mL) was added and most of the THF was removed by rotary evaporation under reduced pressure. The residue was purified by flash column chromatography (silica gel) using ethyl acetate/hexane (7/3) as an eluent to give the desired product (20) (11 mg, 80 percent yield); FAB-MS: MH (298) ; 1H-NMR (CDCl3, 400 MHz) b : 6.72 (d, J = 7.8 Hz, 1H), 6.64 (s, 1H), 6.60 (m 1H), 6.25 (s, 1H), 5.90 (s, 2H), 5.84 (s, 1H), 3.62 (dd, J = 21.3, 15.0 Hz, 2H), 2.94 (s, 3H), 2.86 (m, 1H), 2.58 (m, 2H), 1.06 (d, J = 6.3 Hz, 3H); 13C-NMR (CDCl3, 100 MHz) 8 : 149.4, 148.1, 146.5, 133.1, 126.1, 122.6, 109.9, 108.6, 101.3, 54.4, 46.9, 43.7, 43.3, 20.5. Stage 1: With sodium hydride in tetrahydrofuran, Time= 0.25h, T= 20 °C Stage 2: in tetrahydrofuran, Time= 2h, T= -20 °C Patent; DADE BEHRING INC.; WO2005/58864; (2005); (A1) English View in Reaxys

O HO O

N H

O O

N H

H N

H 2N

O O

NH O

Rx-ID: 28999833 View in Reaxys 12/408 Yield 97 %

Conditions & References Preparation of MDA-AA-14-Boc (47); To a solution of MDA (100 mg, 0.4636 mmol) in MeOH (5 mL) was added Et3N (0.6 ml). The reaction mixture was stirred at room temperature for 15 minutes. The MeOH was removed by rotary evaporation and the residue was put in high vacuum line for 30 minutes. The residue was dissolved in anhydrous AcCN (1 ml) and denoted as the solution A for the next reaction. [0166] To a solution of DSC (251 mg, 0.98 mmol) and Boc-AA-14 (250 mg, 0.718 mmol) in anhydrous AcCN (5 mL) was added Et3N (0.28 ml). The reaction mixture was stirred at room temperature for 2.5 hours and then Et3N (0.2 ml) and solution A were added to the reaction. The reaction was stirred at room temperature for 16 hours. Most of the solvent was removed by rotary evaporation. The residue was purified by flash column chromatography using CH2CI2/MeOH (9/1) as an eluent to give the desired product (47) (230 mg, 97percent yield). 1H-NMR (CDC13, 400 MHz) 6 : 6.72 (b, NH, 1H), 6.67 (d, J = 7.8 Hz, 1 H), 6.64 (s, 1 H), 6.57 (d, J = 7.9 Hz, 1 H), 6.42 (b, NH, 1 H), 5.88 (s, 2H), 5.27 (b, NH, 1H), 4.09 (m, 1H), 3.56-3. 50 (m, 8H), 3.40 (m, 2H), 3.28 (m, 2H), 2.69 (m, 1H), 2.53 (m, 1H), 2.50 (m, 4H), 1.40 (s, 9H), 1.05 (d, J=6.6 Hz, 3H). 13CNMR (CDCI3, 100 MHz) 8 : 172.8, 171.8, 156.5, 147.9, 146.4, 132.4, 122.6, 110.1, 108.4, 101.2, 79.6, 70.6, 70.1, 50.8, 46.8, 42.6, 40.7, 39.7, 32.3, 32.1, 28.8, 20.2. Stage 1: With triethylamine in acetonitrile, Time= 2.5h, T= 20 °C Stage 2: With triethylamine in acetonitrile, Time= 16h, T= 20 °C Patent; DADE BEHRING INC.; WO2005/61482; (2005); (A1) English View in Reaxys

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O O N O O

O N

N H

H 2N

N O

Rx-ID: 23497583 View in Reaxys 13/408 Yield

Conditions & References

66 %

10 :To a MDA (4) (21.0 mg, 0.097 mmol) in THF (4 mL) solution was added N, N-diisopropyl ethyl amine (85 IlL, 0.49 mmol). The mixture was stirred for half-hour under nitrogen before adding-maleimidopropionic acid-NHS-ester (54) (38.9 mg, 0.146 mmol). The reaction was run under nitrogen at room temperature for one hour and forty minutes. The progress of the reaction was monitored by TLC with ethyl acetate as the developing solvent. [0160] Most of organic solvent was removed by rotary evaporator. Trace amount of solvent was removed over high vacuum for one hour. Crude product (92.4 mg) was purified by flash column chromatography with MeOH/CH2CI2 (2/98) as the eluent to give a white solid (55) (21.5 mg, 66percent yield). 1H-NMR (CDCl3, 400 MHz) 8 : 6.66 (m, 5H), 5.93 (s, 2H), 5.45 (d, J= 8 Hz, 1H), 4.16 (m, 1H), 3.81 (t, J=8,2H), 2.67 (m, 2H), 2.47 (t, J=8, 2H), 1.08 (d, J=4. 0 Hz, 3H). With N-ethyl-N,N-diisopropylamine in tetrahydrofuran, Time= 2.16667h, T= 20 °C Patent; DADE BEHRING INC.; WO2005/58864; (2005); (A1) English View in Reaxys

O Cl O

H 2N

N H

O O

Rx-ID: 28999432 View in Reaxys 14/408 Yield

Conditions & References

66 %

2 :To a solution of MDA (4) (30 mg, 0.139 mmol) in DMF (18 mL) was added NaH (18 mg, 0.713 mmol). The reaction mixture was stirred at room temperature for 20 minutes. Methyl bromoacetate (32 mg, 0.209 mmol) was added to the mixture. The mixture was stirred at room temperature for 4 hours. DMF was removed by rotary evaporation and water (10 mL) was added. The aqueous phase was extracted with ethyl acetate (4 x 20 mL). The combined organic phase was dried over MgS04, filtered and concentrated. The residue was purified by flash column chromatography using ethyl acetate/hexane (2/3) as an eluent to give the desired product (11) (23 mg, 66percent yield); FAB-MS: MH + (252) ; 1H-NMR (CDCl3, 400 MHz) 6 : 6.66 (m, 3H), 5.90 (s, 2H), 3.76 (m, 1H), 3.68 (s, 3H), 3.41 (m, 2H), 2.84 (m, 1H), 2.63 (m, 1H), 2.52 (m, 1H), 1.01 (d, J=6.2 Hz, 3H); 13C-NMR (CDCl3, 100 MHz) 6 : 173.3, 148.0, 146.4, 133.1, 122.6, 109.9, 108.6, 101.2, 54.6, 52.8, 52.2, 48.9, 43.8, 20.23. Stage 1: With sodium hydride in DMF (N,N-dimethyl-formamide), Time= 0.333333h, T= 20 °C Stage 2: in DMF (N,N-dimethyl-formamide), Time= 4h, T= 20 °C Patent; DADE BEHRING INC.; WO2005/58864; (2005); (A1) English View in Reaxys

H N

O O

Cl O

NH 2

Rx-ID: 3627479 View in Reaxys 15/408 Yield 92.8 %

Conditions & References With hydrogen, palladium on activated charcoal in methanol, water, Time= 48h, p= 2585.7Torr Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys

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H N

Cl O

NH 2

Rx-ID: 3629146 View in Reaxys 16/408 Yield

Conditions & References

93.9 %

With hydrogen, palladium on activated charcoal in methanol, water, Time= 48h, p= 2585.7Torr Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys

O Cl

H Br

H 2N

O N H

O O

N O

N H

H N

Br O

Rx-ID: 23508397 View in Reaxys 17/408 Yield

Conditions & References

48.3 %

4A :To a stirred solution of MDA (4) (10 mg, 0.04636 mmol) in THF (5 mL) was added diisopropylethylamine (41 IlL, 0.235 mmol). The reaction was stirred at room temperature for 30 minutes. Bromoacetylglycine N-hydroxy succinic ester (40.7 mg, 0.138 mmol) was added to the reaction mixture under argon. The reaction mixture was stirred at room temperature for 1 hour. Water (5 mL) was added and most of the THF was removed by rotary evaporation. The aqueous phase was extracted with CH2CI2 (3 x 20 mL). The combined organic phases were washed with water (10 mL) and dried over MgS04. The organic phase was filtered and evaporated to dryness by rotary evaporation. The residue was purified by flash column chromatography (silica gel) using ethyl acetate/hexane (1/1) as an eluent to give the desired product (19) (8 mg, 48.3 percent yield) ; FAB-MS: MH+ (357,359) ; 1H-NMR (CDCl3, 400 MHz) b : 7.60 (m, NH), 6.64 (m, 3H), 6.00 (m, NH), 5.92 (s, 2H), 4.15 (m, 1H), 4.05 (m, 1H), 3.88 (b s, 3H), 2.69 (m, 2H), 1.12 (d, J=6. 6 Hz, 3H) With N-ethyl-N,N-diisopropylamine in tetrahydrofuran, Time= 1.5h, T= 20 °C Patent; DADE BEHRING INC.; WO2005/58864; (2005); (A1) English View in Reaxys O

H N

O O

N H

Rx-ID: 23508398 View in Reaxys 18/408 Yield

Conditions & References

96 %

2 :To a solution of 11 (23 mg, 0.0951 mmol) in MeOH (12 mL) was added NH40H (1 mL). The reaction mixture was stirred at room temperature for 16 hours. Most of MeOH and NH40H were removed by rotary evaporation. The residue was further dried under high vacuum for removing trace amount of MeOH and NH40H. The residue was dissolved in CH2CI2/MeOH (9/1) and purified by flash column chromatography using CH2CI2/MeOH (3/1) as an eluent to give the desired product (12) (20.8 mg, 96percent yield); FAB-MS : MH+ (237) ; 1H-NMR (CDCb, 400 MHz) 5 : 7.03 (m, 1H), 6.68 (m, 3H), 5.92 (s, 2H), 5.70 (m, 1H), 3.11 (m, 2H), 2. 81 (m, 1H), 2.55 (m, 1H), 1.05 (d, J=6.3 Hz, 3H). With ammonia, water, Time= 16h, T= 20 °C Patent; DADE BEHRING INC.; WO2005/58864; (2005); (A1) English View in Reaxys

O O

H N

O O

O HCl O

N H

Rx-ID: 10841269 View in Reaxys 19/408

8/129

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Yield

Conditions & References

76 %

2; 10 :00233] A suspension of lithium aluminum hydride (3.5 g, 91.3 mmol) in anhydrous tetrahydrofuran (100 mL) was added dropwise to a solution of d2-N-ethoxycarbonyl-l-(3,4- methylenedioxyphenyl)-2-aminopropane (7.7 g, 30.4 mmol) in anhydrous tetrahydrofuran (80 mL). The mixture was heated to reflux for 2 hours, cooled to ambient temperature, and quenched with water. The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and the solvent was removed to yield the title compound (4.4 g, 76percent yield), which was dissolved in anhydrous diethyl ether and treated with hydrochloric gas to afford d2-3,4- methylenedioxyphenyl-2-aminopropane hydrochloride salt (5 g), as a white solid. 1H NMR (300MHz, CDCl3), δ 9.67 (s, 2H), 6.76-6.66 (m, 3H), 3.40-3.27 (m, 3H), 2.81-2.77 (m, IH), 2.70 (s, 3H), 1.35 (d, 3H, 7=6.6 Hz); LC-MS: m/z=196 [M+H] +. Stage 1: With lithium aluminium tetrahydride in tetrahydrofuran, Time= 2h, Heating / reflux Stage 2: With water in tetrahydrofuran Stage 3: With hydrogenchloride in diethyl ether Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English View in Reaxys O O

OH HO

S N

O N O

O S O N

Rx-ID: 36967716 View in Reaxys 20/408 Yield

Conditions & References

78 %

With 3-monochlorophenol, tri-1-napthylphosphine, caesium carbonate, bis(dibenzylideneacetone)-palladium(0) in tetrahydrofuran, Time= 36h, T= 35 °C , Inert atmosphere, regioselective reaction Duda, Megan L.; Michael, Forrest E.; Journal of the American Chemical Society; vol. 135; nb. 49; (2013); p. 18347 - 18349 View in Reaxys

H N

O O

N H

Rx-ID: 9037704 View in Reaxys 21/408 Yield 98 %

Conditions & References With lithium aluminium tetrahydride in tetrahydrofuran, Time= 2h, Heating Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys 4.1.14. (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine,(R)-10a, (R)-MDMA General procedure: A solution of (R)-9a (106 mg, 0.42 mmol) in anh THF (5 mL) was added dropwise to a suspension of LiAlH4 (0.048 g, 1.26 mmol,3 equiv) in anh THF (3 mL). The mixture was refluxed with stirring for 4 h and then allowed to cool to room temperature. The excess LiAlH4 was destroyed by slow addition of water at 0 °C. Ethyl acetate was added, extracted with NH4Cl (5 mL) and NaCl (5 mL). The organic layers were dried over anhydrous MgSO4, filtered and the solvent was removed under reduced pressure affording (R)-10a(70 mg, 0.36 mmol) in 85percent of yield as a colourless oil. This compound was then dissolved in anhydrous diethyl ether (4 mL) and 2 M HCl in diethyl ether was added dropwise, yielding the corresponding hydrochloride HCl (R)-10a as a white solid. With lithium aluminium tetrahydride in tetrahydrofuran, Time= 4h, Reflux

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Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

O O H 2N O F S O F F

O H N

O S

F F

Rx-ID: 38105388 View in Reaxys 22/408 Yield

Conditions & References

59 %

With 2,6-dimethylpyridine, 9-mesityl-10-methylacridinium tetrafluoroborate, diphenyldisulfane in dichloromethane, Time= 96h, T= 23 °C , Inert atmosphere, Irradiation, regioselective reaction Nguyen, Tien M.; Manohar, Namita; Nicewicz, David A.; Angewandte Chemie - International Edition; vol. 53; nb. 24; (2014); p. 6198 - 6201; Angew. Chem.; vol. 126; nb. 24; (2014); p. 6312 - 6315,4 View in Reaxys O

NH 2

Rx-ID: 10841267 View in Reaxys 23/408 Yield

Conditions & References 2; 8 :00231] Anhydrous tetrahydrofuran (300 mL) and lithium aluminum hydride (8.9 g,236 mmol) were introduced into a three-neck round bottom flask under an argon atmosphere and cooled to 00C. A solution of d2-l-(3,4-methylenedioxyphenyl)-2-nitropropene (24.7 g, 118 mmol) in 100 mL of anhydrous tetrahydrofuran was slowly added to the suspension, while keeping the temperature below 150C. The resulting mixture was heated to reflux for 16 hours. Excess lithium aluminum hydride was quenched with water and the organic phase was separated, dried over anhydrous sodium sulfate, filtered and the solution was concentrated to yield the title compound (20 g) as brown oil which was used in next reaction without further <n="67"/>purification. Stage 1: With lithium aluminium tetrahydride in tetrahydrofuran, Time= 16h, T= 0 - 15 °C , Heating / reflux Stage 2: With water in tetrahydrofuran Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English View in Reaxys

H N

H H

O 2H

N 2 H H

Rx-ID: 10841271 View in Reaxys 24/408 Yield

Conditions & References 15; 16 :[00238] The procedure is carried out using the methods described by PojerTetrahedron Letters 1984, 25(23), 2507-2508 and references cited therein. A stirred solution of d5-N-methyl-l-[3,4-methylenedioxyphenyl]-2-aminopropane (0.1 g) is heated at 70-1000C for 18 hours with deuterated Raney nickel (2 mL wet) in tetrahydrofuran or deuterium oxide (5 mL). The reaction is cooled, filtered to remove the Raney nickel and the residue is treated with dilute deuterium chloride in deuterium oxide and extracted into ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the solvent is removed under reduced pressure to give the title product; Example 16 Deuterated Raney Nickel[00239] The procedure is carried out using the methods described by Khan, J. Am.Chem. Soc. 1952, 74, 3018-3022 and references cited therein. Raney nickel (25 g, still wet with dioxane) is washed once with a 25 mL portion of dioxane by centrifugation and the nickel is then suspended in 10 mL of deuterium oxide and allowed to stand in a stoppered tube for 48 hours. The nickel is occasionally stirred a few times throughout the equilibration period. It is then washed with three 25 mL portions of dioxane and transferred to the reaction vessel of a Joshel apparatus (250 mL) with the help of about 125 mL of dioxane. To this catalyst in the reaction vessel is added 5 mL of

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deuterium oxide. The stopcock above the reaction vessel is then closed, the system evacuated and deuterium gas introduced. About 100 mL of deuterium gas is collected in the 500 mL reservoir. After closing all stopcocks to the outside, the stopcock over the reaction vessel is opened and the catalyst in dioxane is agitated in the presence of deuterium gas under slight pressure for two hours. The process is repeated three times, the system being flushed each time with dry oxygen-free nitrogen and filled with fresh deuterium. Nickel prepared in this manner is stored in purified dioxane containing a small amount of deuterium oxide. Stage 1: With deuterated Raney nickel, Time= 18h, T= 70 - 100 °C Stage 2: With hydrogen chloride in water-d2 Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English View in Reaxys

N H

Rx-ID: 11228290 View in Reaxys 25/408 Yield

Conditions & References

76 %

Stage 1: With hydroxylamine in methanol, Time= 0.5h, T= 20 °C Stage 2: With hydrogenchloride, sodium cyanoborohydride in methanol, Time= 72h, T= 20 °C , pH= 4 - 6, Further stages. Montgomery; Buon; Eibauer; Guiry; Keenan; McBean; British Journal of Pharmacology; vol. 152; nb. 7; (2007); p. 1121 - 1130 View in Reaxys O O

O HO

H N

O OH

O O O

O N

Rx-ID: 23488701 View in Reaxys 26/408 Yield

Conditions & References 2 :To a solution of 12 (8 mg, 0.0337 mmol) in DMF (0.5 mL) was added EDAC (19 mg, 0.0991 mmol) and NHS (19 mg, 0.165 mmol). The reaction was stirred at room temperature under argon for 16 hours. The progress of the reaction was monitored by TLC (silica gel, MeOH/CH2CI2 = 1/9). The activated hapten (13) was added drop wise under argon to 5 mL of sodium phosphate solution (0. 1 M, pH = 8.0) of KLH (20 mg) at 0 °C under argon. The pH value changed during the addition and 0.1 N of NaOH aqueous solution was used to maintain the pH = 8.0. After completed the addition, the conjugate was allowed to stir at room temperature for 4 hours. The conjugate (14) was dialyzed against Dulbecco's phosphate buffered saline (pH = 7.0, 3 Liters) prepared from Dulbecco's phosphate buffered saline (Sigma buffer, 400 mL) diluting with DI water (2600 mL) at 4 °C for 4 hours. The dialyzing procedure was repeated with fresh buffer solution for 16,24 and 40 hours. Finally, the conjugate was dialyzed with sodium phosphate buffer solution (10 mM, pH = 7. 0) two times (3 hours and 4 hours). The concentration of protein was measured by using BCA Protein Concentration Assay and the TNBS method was used for hapten number determination. The immunogen (14) has a concentration of 2.63 mg/mL with the hapten number of 1490, and used for the immunization of mice for antibody production. With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride in DMF (N,N-dimethyl-formamide), Time= 16h, T= 20 °C Patent; DADE BEHRING INC.; WO2005/58864; (2005); (A1) English View in Reaxys

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O OH H 2N

H N

O O

N H

NH OH

Rx-ID: 25468786 View in Reaxys 27/408 Yield

Conditions & References

90%

1 : 1-(R)-(4-hydroxy-3-(p-methoxybenzylamino)phenyl)-2-[(1(S)-methyl-2-(3,4-methylenedioxyphenyl)ethyl)amino]ethanol (X) 1-(R)-(4-hydroxy-3-(p-methoxybenzylamino)phenyl)-2-[(1(S)-methyl-2-(3,4-methylenedioxyphenyl)ethyl)amino]ethanol (X) 2 ml (16 mmol) of p-anisaldehyde was added to the previously obtained methanol solution of the R,S,S-isomer of (IX). After reflux for 30 min, 30 mg of PtO2 was added and the mixture hydrogenated at 50 psi for 1.5 hrs. Yield of crude product (90percent pure) was 2.3 g. With PtO2 Patent; Aktiebolaget Draco; EP390762; (1990); (A1) English View in Reaxys

H N

N H

Rx-ID: 37966358 View in Reaxys 28/408 Yield

Conditions & References 4.1.14. (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine,(R)-10a, (R)-MDMA A solution of (R)-9a (106 mg, 0.42 mmol) in anh THF (5 mL) was added dropwise to a suspension of LiAlH 4 (0.048 g, 1.26 mmol,3 equiv) in anh THF (3 mL). The mixture was refluxed with stirring for 4 h and then allowed to cool to room temperature. The excess LiAlH4 was destroyed by slow addition of water at 0 °C. Ethyl acetate was added, extracted with NH4Cl (5 mL) and NaCl (5 mL). The organic layers were dried over anhydrous MgSO4, filtered and the solvent was removed under reduced pressure affording (R)-10a(70 mg, 0.36 mmol) in 85percent of yield as a colourless oil. This compound was then dissolved in anhydrous diethyl ether (4 mL) and 2 M HCl in diethyl ether was added dropwise, yielding the corresponding hydrochloride HCl (R)-10a as a white solid. With hydrogenchloride in diethyl ether Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

N H

Rx-ID: 37966359 View in Reaxys 29/408 Yield 41 mg

Conditions & References 4.1.14. (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine,(R)-10a, (R)-MDMA General procedure: A solution of (R)-9a (106 mg, 0.42 mmol) in anh THF (5 mL) was added dropwise to a suspension of LiAlH4 (0.048 g, 1.26 mmol,3 equiv) in anh THF (3 mL). The mixture was refluxed with stirring for 4 h and then allowed to cool to room temperature. The excess LiAlH4 was destroyed by slow addition of water at 0 °C. Ethyl acetate was added, extracted with NH4Cl (5 mL) and NaCl (5 mL). The organic layers were dried over anhydrous MgSO4, filtered and the solvent was removed under reduced pressure affording (R)-10a(70 mg, 0.36 mmol) in 85percent of yield as a colourless oil. This compound was then dissolved in anhydrous diethyl ether (4 mL) and 2 M HCl in diethyl ether was added dropwise, yielding the corresponding hydrochloride HCl (R)-10a as a white solid.

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With hydrogenchloride in diethyl ether Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

O N

N H

Rx-ID: 3615077 View in Reaxys 30/408 Yield

Conditions & References With hydrogen, W-2 Raney nickel in ethanol, Time= 24h, p= 2585.7Torr , Yield given Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys

O O

N NH O

Rx-ID: 10472680 View in Reaxys 31/408 Yield 88 %

Conditions & References With Na-selectride in tetrahydrofuran, Time= 1.5h, T= -5 °C Manaka, Tomoyuki; Nagayama, Shin-Ichiro; Desadee, Wannaporn; Yajima, Naoki; Kumamoto, Takuya; Watanabe, Toshiko; Ishikawa, Tsutomu; Kawahata, Masatoshi; Yamaguchi, Kentaro; Helvetica Chimica Acta; vol. 90; nb. 1; (2007); p. 128 - 142 View in Reaxys

O O

NH 2

Rx-ID: 270051 View in Reaxys 32/408 Yield 87 %

Conditions & References With lithium aluminium tetrahydride Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys With hydrogenchloride, ethanol, acetic acid, Electrolysis Bruckner; Justus Liebigs Annalen der Chemie; vol. 518; (1935); p. 226,241 View in Reaxys With lithium aluminium tetrahydride, diethyl ether Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys With lithium aluminium tetrahydride, diethyl ether, benzene Benington et al.; Journal of Organic Chemistry; vol. 23; (1958); p. 1979,1980

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View in Reaxys With lithium aluminium tetrahydride, sulfuric acid in tetrahydrofuran, Ambient temperature Glennon, Richard A.; Raghupathi, Reva; Bartyzel, Piotr; Teitler, Milt; Leonhardt, Sigrun; Journal of Medicinal Chemistry; vol. 35; nb. 4; (1992); p. 734 - 740 View in Reaxys With lithium aluminium tetrahydride in diethyl ether Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354 View in Reaxys

O O

O Z

N H

Rx-ID: 25203855 View in Reaxys 33/408 Yield

Conditions & References 10.3 : EXAMPLE 10 (3) A mixture of the α-(α-methyl-3,4-methylenedioxyphenethylimino)-2-methoxyacetophenone solution obtained in paragraph (2), 1.73 g of sodium borohydride and 30 ml of ethanol is treated in the same manner as described in Example 1-(3), whereby α-[(α-methyl-3,4-methylenedioxyphenethylamino)methyl]-2-methoxybenzylalcohol [the mixture of two diastereoisomers] is obtained as a crude oil. With sodium borohydride in ethanol Patent; Tanabe Seiyaku Co., Ltd.; US4490392; (1984); (A1) English View in Reaxys

O O

N H

Rx-ID: 25203856 View in Reaxys 34/408 Yield

Conditions & References 12.3 : EXAMPLE 12 (3) A mixture of the α-(α-methyl-3,4-methylenedioxyphenethylimino)-2-benzyloxyacetophenone solution obtained in paragraph (2), 1.25 g of sodium borohydride and 30 ml of ethanol is treated in the same manner as described in Example 1-(3), whereby α-[(α-methyl-3,4-methylenedioxyphenethylamino)methyl]-2-benzyloxybenzylalcohol [the mixture of two diastereoisomers] is obtained as a caramel. With sodium borohydride in ethanol Patent; Tanabe Seiyaku Co., Ltd.; US4490392; (1984); (A1) English View in Reaxys

(v1)

Pol

O H 2N

N H

O OH

Pol

(v1)

Rx-ID: 23495871 View in Reaxys 35/408

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Yield

Conditions & References a) MDA Latex Particle (44); MDA particle reagents of various levels of immobilization are prepared by dropwise and sequential addition of GAFAC (0.507-0. 529 mL, 14.7percent stock solution, 0. 7percent in reaction), MDA (0.139-0. 580 mL, 77.27 mM stock solution; 1,2, 3, and 4 mM in reaction), and DA-10 (0.099-0. 104 mL, 324.4 mM stock solution, 3 mM in reaction) into diafiltered particle raw material (PRM) (10 ml, 10.3percent stock solution, 9.62-9. 24percent solids in reaction). The pH is measured and adjusted to 9.2. The reactions are carried out at 70°C for 18 hours. Each supernatant (10 ml) is separated by centrifugation (28,000 rpm) and decanting. Fresh wash buffer (20 ml, 1.0percent GAFAC, 15 mM phosphate buffer, 0.2percent Prolin, 0.006percent neomycin sulfate) is added to each reaction tube and the particle reagents resuspended by sonication. This supernatant exchange process is repeated 3 more times. The final pellets are resuspended into wash buffer (20 ml) resulting in particle concentrate solutions (20 ml, 50 mg/ml). With 2,2'-(ethylenedioxy)bis(ethylamine) Solid phase= latex, Time= 18h, T= 70 °C , pH= 9.2 Patent; DADE BEHRING INC.; WO2005/61482; (2005); (A1) English View in Reaxys O

H N

N H

NH 2 (v1)

H N

N H

Pol

O O

N H

Pol

(v1)

Rx-ID: 23506694 View in Reaxys 36/408 Yield

Conditions & References a) MDA-AA-14-NH ? Latex Particle (49); MDA-AA-14-NH2 particle reagents of various level of immobilization are prepared by dropwise and sequential addition of GAFAC (0.507-0. 527 ml, 14.7percent stock solution, 0.7percent in reaction), MDA-AA-14-NH2 (0.132-0. 549 mi, 81.4 mM stock solution; 1,2, 3, and 4 mM in reaction), and DA-10 (0.099-0. 103 ml, 324.4 mM stock solution, 3 mM in reaction) into diafiltered particle raw material (10 ml, 10.3percent stock solution, 9.62-9. 24percent solids in reaction). The pH value is measured and adjusted to 9.2. The reactions are carried out at 70°C for 18 hours. Each supernatant (10 ml) is separated by centrifugation (28,000 rpm) and decanting. Fresh wash buffer (20 ml, 1.0percent GAFAC, 15 mM phosphate buffer, 0.2percent Prolin, 0.006percent neomycin sulfate) is added to each reaction tube and the particle reagents resuspended by sonication. This supernatant exchange process is repeated 3 more times. The final pellets are resuspended into wash buffer (20 ml) resulting in particle concentrate solutions (20 ml, 50 mg/mL). With 2,2'-(ethylenedioxy)bis(ethylamine) Solid phase= latex, Time= 18h, T= 70 °C , pH= 9.2 Patent; DADE BEHRING INC.; WO2005/61482; (2005); (A1) English View in Reaxys O

O O

H 2N

H N

N H

N O

Rx-ID: 24003726 View in Reaxys 37/408 Yield

Conditions & References 5 : Preparation of 4'-maleimidobutyl-3,4-methylenedioxyamphetamine (MB-MDA) Example 5 Preparation of 4'-maleimidobutyl-3,4-methylenedioxyamphetamine (MB-MDA) AB-MDA (51 mg) was dissolved in tetrahydrofuran (2.5 ml). Saturated sodium bicarbonate solution (1.5 ml) was added to the reaction mixture. Methoxycarbonylmaleimide (17 mg) was added to the reaction mixture. An appropriately sized magnetic stirrer was added to the reaction mixture. The reaction mixture was stirred for 2 hours. At this point the reaction was complete. Water (15 ml) and ethylacetate (25 ml) were added to the reaction mixture. The mixture was transferred into a separatory funnel.

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The organic phase was washed with water (10 ml) and saturated sodium chloride solution (15 ml). The organic phase was dried over sodium sulfate (2 g). The solvent was removed by rotary evaporation. The product was purified by HPLC using water and acetonitrile (both containing 0.1percent TFA) as mobile phase. A semipreparative C4 column was used as a stationary phase. The main peak (Rf=14 min) was collected and lyophilzed. This gave 18.4 mg of the product. Mass Spectrum (El), m/z 329 (M-1), 315 (M-15), 195 (M-135), 1H NMR (CD3OD), δ (ppm), 6.83 (s, 2H, =CH-), 6.69-6.79 (m, 3H, Ar-H), 5.9 (s, 2H, O-CH2-O-), 3.55 (t, 3H, Ar-CH2-), 3.41 (m, 1H N-CH-), 3.06 (m, 4H, N-CH2-), 1.67 (m, 4H, -CH2-), 1.21 (d, 3H, -CH3). With sodium hydrogencarbonate, trifluoroacetic acid in tetrahydrofuran, water, ethyl acetate, acetonitrile Patent; Microgenics Corporation; US2003/207469; (2003); (A1) English View in Reaxys

O O

N H

Rx-ID: 5070516 View in Reaxys 38/408 Yield

Conditions & References

49 %, 47 %

With trifluorormethanesulfonic acid, 5A molecular sieve, chloranil, [NBu4][ReO4] in 1,2-dichloro-ethane, Time= 1.5h, Heating, Cyclization, Beckmann rearrangement Kusama; Yamashita; Uchiyama; Narasaka; Bulletin of the Chemical Society of Japan; vol. 70; nb. 5; (1997); p. 965 - 975 View in Reaxys O

H N

HO O

O Cl

O OH Cl

N H

Rx-ID: 3018006 View in Reaxys 39/408 Yield

Conditions & References With hydrogen, palladium on activated charcoal in methanol, Time= 11.5h Grisar; Claxton; Bare; Dage; Cheng; Woodward; Journal of Medicinal Chemistry; vol. 24; nb. 3; (1981); p. 327 336 View in Reaxys OH

H N

O O

NH 2 OH

O O

N H

Rx-ID: 3056963 View in Reaxys 40/408 Yield

Conditions & References With ammonia, sodium methylate in methanol, Time= 72h, T= 25 °C Grisar; Claxton; Bare; Dage; Cheng; Woodward; Journal of Medicinal Chemistry; vol. 24; nb. 3; (1981); p. 327 336 View in Reaxys

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N H

Rx-ID: 18817247 View in Reaxys 41/408 Yield

Conditions & References Reaction Steps: 2 1: benzene / 7 h / Heating 2: H2 / W-2 Raney nickel / ethanol / 24 h / 2585.7 Torr With hydrogen, W-2 Raney nickel in ethanol, benzene Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys

O Cl

NH 2

Rx-ID: 18817248 View in Reaxys 42/408 Yield

Conditions & References Reaction Steps: 2 1: 2.) H2 / 2.) W-2 Raney nickel / 1.) benzene, reflux, 7 h, 2.) ethanol, 50 psi, 24 h 2: 92.8 percent / H2 / 10percent Pd/C / methanol; H2O / 48 h / 2585.7 Torr With hydrogen, palladium on activated charcoal, W-2 Raney nickel in methanol, water Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys

H 2N

N H

Rx-ID: 18823531 View in Reaxys 43/408 Yield

H 2N

N H

NH 2

Rx-ID: 266067 View in Reaxys 44/408 Yield

Conditions & References With ethanol, acetic acid, platinum, p= 2942.03Torr , Hydrogenation Biel et al.; Journal of the American Chemical Society; vol. 81; (1959); p. 2805,2810, 2813 View in Reaxys

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O O

H 2N

N H

Rx-ID: 1802471 View in Reaxys 45/408 Yield

Conditions & References With triethylamine in tetrahydrofuran, Time= 2h, T= 25 °C Grisar; Claxton; Bare; Dage; Cheng; Woodward; Journal of Medicinal Chemistry; vol. 24; nb. 3; (1981); p. 327 336 View in Reaxys

HN O

NH 2

Rx-ID: 4743503 View in Reaxys 46/408 Yield

Conditions & References With hydrogen, triethylamine, palladium on activated charcoal in ethanol, Time= 3h, Ambient temperature, Yield given Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

N H

Rx-ID: 4743870 View in Reaxys 47/408 Yield

Conditions & References With hydrogen, triethylamine, palladium on activated charcoal in ethanol, Time= 2h, Ambient temperature, Yield given Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

H N

O N

O O

N H

Rx-ID: 4744432 View in Reaxys 48/408 Yield

Conditions & References With hydrogen, triethylamine, palladium on activated charcoal in ethanol, Time= 4h, Ambient temperature, Yields of byproduct given Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys With hydrogen, triethylamine, palladium on activated charcoal in ethanol, Time= 4h, Ambient temperature, Yield given Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

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N H

Rx-ID: 4744463 View in Reaxys 49/408 Yield

Conditions & References With hydrogen, triethylamine, palladium on activated charcoal in ethanol, Time= 5h, Ambient temperature, Yield given Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

OH O

N H

Rx-ID: 17205203 View in Reaxys 50/408 Yield

Conditions & References Reaction Steps: 4 1: pyridine / diethyl ether / 5 h / Ambient temperature 3: 96 percent / Et3N / CH2Cl2; toluene / 0.5 h / Ambient temperature 4: Et3N, H2 / 10percent Pd/C / ethanol / 4 h / Ambient temperature With pyridine, hydrogen, triethylamine, palladium on activated charcoal in diethyl ether, ethanol, dichloromethane, toluene Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

OH O

N H

Rx-ID: 17205206 View in Reaxys 51/408 Yield

Conditions & References Reaction Steps: 4 1: pyridine / diethyl ether / 5 h / Ambient temperature 3: 93 percent / Et3N / CH2Cl2; toluene / 0.5 h / Ambient temperature 4: Et3N, H2 / 10percent Pd/C / ethanol / 5 h / Ambient temperature With pyridine, hydrogen, triethylamine, palladium on activated charcoal in diethyl ether, ethanol, dichloromethane, toluene Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

OH O

N H

Rx-ID: 17205210 View in Reaxys 52/408 Yield

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With pyridine, hydrogen, triethylamine, palladium on activated charcoal in diethyl ether, ethanol, dichloromethane, toluene Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

O O

N H

Rx-ID: 17217402 View in Reaxys 53/408 Yield

Conditions & References Reaction Steps: 3 2: 96 percent / Et3N / CH2Cl2; toluene / 0.5 h / Ambient temperature 3: Et3N, H2 / 10percent Pd/C / ethanol / 4 h / Ambient temperature With hydrogen, triethylamine, palladium on activated charcoal in ethanol, dichloromethane, toluene Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

O O

N H

Rx-ID: 17217405 View in Reaxys 54/408 Yield

Conditions & References Reaction Steps: 3 2: 93 percent / Et3N / CH2Cl2; toluene / 0.5 h / Ambient temperature 3: Et3N, H2 / 10percent Pd/C / ethanol / 5 h / Ambient temperature With hydrogen, triethylamine, palladium on activated charcoal in ethanol, dichloromethane, toluene Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

O O

N H

Rx-ID: 17217406 View in Reaxys 55/408 Yield

OH H 2N

NH 2

Rx-ID: 17219718 View in Reaxys 56/408

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Yield

Conditions & References Reaction Steps: 2 1: 97 percent / Et3N / CH2Cl2; toluene / 0.5 h / Ambient temperature 2: Et3N, H2 / 10percent Pd/C / ethanol / 3 h / Ambient temperature With hydrogen, triethylamine, palladium on activated charcoal in ethanol, dichloromethane, toluene Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

H N

N H

Rx-ID: 17233407 View in Reaxys 57/408 Yield

Conditions & References Reaction Steps: 2 1: 91 percent / Et3N / CH2Cl2; toluene / 0.5 h / Ambient temperature 2: Et3N, H2 / 10percent Pd/C / ethanol / 2 h / Ambient temperature With hydrogen, triethylamine, palladium on activated charcoal in ethanol, dichloromethane, toluene Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

H N

OH O

N H

Rx-ID: 17233427 View in Reaxys 58/408 Yield

Conditions & References Reaction Steps: 2 1: 93 percent / Et3N / CH2Cl2; toluene / 0.5 h / Ambient temperature 2: Et3N, H2 / 10percent Pd/C / ethanol / 5 h / Ambient temperature With hydrogen, triethylamine, palladium on activated charcoal in ethanol, dichloromethane, toluene Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

H N

OH O

N H

Rx-ID: 17233476 View in Reaxys 59/408 Yield

Conditions & References Reaction Steps: 2 1: 96 percent / Et3N / CH2Cl2; toluene / 0.5 h / Ambient temperature 2: Et3N, H2 / 10percent Pd/C / ethanol / 4 h / Ambient temperature With hydrogen, triethylamine, palladium on activated charcoal in ethanol, dichloromethane, toluene Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

H N

OH O

N H

Rx-ID: 17233477 View in Reaxys 60/408

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Yield

O O

N O

S O N

Rx-ID: 36967746 View in Reaxys 61/408 Yield

Conditions & References Reaction Steps: 2 1: triethylamine / dichloromethane / 0.42 h / -78 - 0 °C / |Inert atmosphere; |Sealed tube 2: bis(dibenzylideneacetone)-palladium(0); caesium carbonate; tri-1-napthylphosphine; 3-monochlorophenol / tetrahydrofuran / 36 h / 35 °C / |Inert atmosphere With 3-monochlorophenol, tri-1-napthylphosphine, caesium carbonate, triethylamine, bis(dibenzylideneacetone)-palladium(0) in tetrahydrofuran, dichloromethane Duda, Megan L.; Michael, Forrest E.; Journal of the American Chemical Society; vol. 135; nb. 49; (2013); p. 18347 - 18349 View in Reaxys

O 13 C O

13C

H C

C H

O 13 C

13CH

13C

H C

C H

13C

NH 2

HCl

Rx-ID: 38014823 View in Reaxys 62/408 Yield 32 %

Conditions & References Stage 1: With methanol, ammonium acetate, sodium cyanoborohydride, T= 20 °C , Inert atmosphere Stage 2: With hydrogenchloride in diethyl ether, pH= 4 Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

O Cl H 2N

F F

O F

N H

Rx-ID: 41147692 View in Reaxys 63/408 Yield

Conditions & References With 1,1,1,3,3,3-hexamethyl-disilazane in ethyl acetate, Time= 0.333333h, T= 80 °C Molnár, Borbála; Fodor, Blanka; Boldizsár, Imre; Molnár-Perl, Ibolya; Analytical Chemistry; vol. 87; nb. 20; (2015); p. 10188 - 10192 View in Reaxys

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O O

N H

Rx-ID: 14955721 View in Reaxys 64/408 Yield

Conditions & References Reaction Steps: 7 1.1: 96 percent / NH4OAc / 17 h / Heating 2.1: 71 percent / LiAlH4 / tetrahydrofuran / 4 h / Heating 3.1: dibenzoyl-L-(-)-tartaric acid / methanol / Heating 3.2: base 4.1: Et3N; DMAP / tetrahydrofuran / 6 h / 20 °C 5.1: 95 percent / H2 / Pd/C / methanol 6.1: 95 percent / cesium carbonate / dimethylformamide / 2 h 7.1: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / Heating With dmap, lithium aluminium tetrahydride, ammonium acetate, hydrogen, caesium carbonate, triethylamine, O,O'dibenzoyl-L-tartaric acid, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethyl-formamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys Reaction Steps: 9 1: ammonium acetate / 17 h / |Reflux 2: iron; iron(III) chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 3: titanium(IV) tetraethanolate / tetrahydrofuran / 5 h / |Reflux 4: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 5: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 6: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 7: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 8: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 9: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With hydrogenchloride, dmap, iron(III) chloride, titanium(IV) tetraethanolate, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, ammonium acetate, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, ethanol, water, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O

O N H

Rx-ID: 14955725 View in Reaxys 65/408 Yield

Conditions & References Reaction Steps: 6 1.1: 96 percent / NH4OAc / 17 h / Heating 2.1: 71 percent / LiAlH4 / tetrahydrofuran / 4 h / Heating 3.1: dibenzoyl-L-(-)-tartaric acid / methanol / Heating 3.2: base 4.1: Et3N; DMAP / tetrahydrofuran / 6 h / 20 °C 5.1: 95 percent / H2 / Pd/C / methanol

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6.1: 95 percent / cesium carbonate / dimethylformamide / 2 h With dmap, lithium aluminium tetrahydride, ammonium acetate, hydrogen, caesium carbonate, triethylamine, O,O'dibenzoyl-L-tartaric acid, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethyl-formamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys Reaction Steps: 8 1: ammonium acetate / 17 h / |Reflux 2: iron; iron(III) chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 3: titanium(IV) tetraethanolate / tetrahydrofuran / 5 h / |Reflux 4: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 5: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 6: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 7: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 8: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C With hydrogenchloride, dmap, iron(III) chloride, titanium(IV) tetraethanolate, sodium tetrahydroborate, palladium 10 on activated carbon, ammonium acetate, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4dioxane, methanol, ethanol, water, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H NH 2

O O

N H

Rx-ID: 14971005 View in Reaxys 66/408 Yield

Conditions & References Reaction Steps: 4 1: Et3N; DMAP / tetrahydrofuran / 6 h / 20 °C 2: 95 percent / H2 / Pd/C / methanol 3: 95 percent / cesium carbonate / dimethylformamide / 2 h 4: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / Heating With dmap, lithium aluminium tetrahydride, hydrogen, caesium carbonate, triethylamine, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethyl-formamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys Reaction Steps: 4 1: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 2: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 3: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With dmap, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

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H NH 2

N H

Rx-ID: 14971007 View in Reaxys 67/408 Yield

Conditions & References Reaction Steps: 3 1: Et3N; DMAP / tetrahydrofuran / 6 h / 20 °C 2: 95 percent / H2 / Pd/C / methanol 3: 95 percent / cesium carbonate / dimethylformamide / 2 h With dmap, hydrogen, caesium carbonate, triethylamine, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethyl-formamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys Reaction Steps: 3 1: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 2: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 3: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C With dmap, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O O

N H

Rx-ID: 14990048 View in Reaxys 68/408 Yield

Conditions & References Reaction Steps: 3 1: 95 percent / H2 / Pd/C / methanol 2: 95 percent / cesium carbonate / dimethylformamide / 2 h 3: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / Heating With lithium aluminium tetrahydride, hydrogen, caesium carbonate, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethyl-formamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys Reaction Steps: 3 1: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 2: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate in tetrahydrofuran, methanol, N,N-dimethyl-formamide

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H N

N H

Rx-ID: 14990049 View in Reaxys 69/408 Yield

Conditions & References Reaction Steps: 2 1: 95 percent / H2 / Pd/C / methanol 2: 95 percent / cesium carbonate / dimethylformamide / 2 h With hydrogen, caesium carbonate, palladium on activated charcoal in methanol, N,N-dimethyl-formamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys Reaction Steps: 2 1: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 2: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C With palladium 10 on activated carbon, hydrogen, caesium carbonate in methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H 2N

O N H

Rx-ID: 150249 View in Reaxys 70/408 Yield 90 %

Conditions & References With pyridine, Time= 10h, Ambient temperature Rastogi, Shri Niwas; Kansal, V. K.; Bhaduri, A. P.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 22; nb. 3; (1983); p. 234 - 237 View in Reaxys

58 %

With pyridine, Time= 18h, Ambient temperature Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys Elks; Hey; Journal of the Chemical Society; (1943); p. 15 View in Reaxys

O Si I

N F

H 2N

O Si

N H

Rx-ID: 41147691 View in Reaxys 71/408

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Yield

Conditions & References With pyridine, hydrogenchloride in water, ethyl acetate, Time= 1h, T= 90 °C , Temperature Molnár, Borbála; Fodor, Blanka; Boldizsár, Imre; Molnár-Perl, Ibolya; Analytical Chemistry; vol. 87; nb. 20; (2015); p. 10188 - 10192 View in Reaxys

(+-)-2-piperonyl-propionic acid amide O

NH 2

Rx-ID: 5446366 View in Reaxys 72/408 Yield

Conditions & References With sodium hypochlorite, Erwaermen des Reaktionsgemisches mit wss. Kalilauge Hey; Williams; Journal of the Chemical Society; (1951); p. 1527,1529 View in Reaxys Ide; Buck; Journal of the American Chemical Society; vol. 62; (1940); p. 425,427 View in Reaxys

NH 2 O

N H

Rx-ID: 14960803 View in Reaxys 73/408 Yield

Conditions & References Reaction Steps: 5 1.1: dibenzoyl-L-(-)-tartaric acid / methanol / Heating 1.2: base 2.1: Et3N; DMAP / tetrahydrofuran / 6 h / 20 °C 3.1: 95 percent / H2 / Pd/C / methanol 4.1: 95 percent / cesium carbonate / dimethylformamide / 2 h 5.1: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / Heating With 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, hydrogen, caesium carbonate, triethylamine, (2R,3S)-(-)-di-O-benzoyl tartaric acid, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethylformamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys

NH 2 O O

O O

O N H

Rx-ID: 14960805 View in Reaxys 74/408 Yield

Conditions & References Reaction Steps: 4 1.1: dibenzoyl-L-(-)-tartaric acid / methanol / Heating 1.2: base 2.1: Et3N; DMAP / tetrahydrofuran / 6 h / 20 °C 3.1: 95 percent / H2 / Pd/C / methanol 4.1: 95 percent / cesium carbonate / dimethylformamide / 2 h

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With 4-(N,N-dimethlyamino)pyridine, hydrogen, caesium carbonate, triethylamine, (2R,3S)-(-)-di-O-benzoyl tartaric acid, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethyl-formamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys O N O

N H

Rx-ID: 14961279 View in Reaxys 75/408 Yield

Conditions & References Reaction Steps: 6 1.1: 71 percent / LiAlH4 / tetrahydrofuran / 4 h / Heating 2.1: dibenzoyl-L-(-)-tartaric acid / methanol / Heating 2.2: base 3.1: Et3N; DMAP / tetrahydrofuran / 6 h / 20 °C 4.1: 95 percent / H2 / Pd/C / methanol 5.1: 95 percent / cesium carbonate / dimethylformamide / 2 h 6.1: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / Heating With 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, hydrogen, caesium carbonate, triethylamine, (2R,3S)-(-)-di-O-benzoyl tartaric acid, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethylformamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys O N O

O O

O N H

Rx-ID: 14961281 View in Reaxys 76/408 Yield

Conditions & References Reaction Steps: 5 1.1: 71 percent / LiAlH4 / tetrahydrofuran / 4 h / Heating 2.1: dibenzoyl-L-(-)-tartaric acid / methanol / Heating 2.2: base 3.1: Et3N; DMAP / tetrahydrofuran / 6 h / 20 °C 4.1: 95 percent / H2 / Pd/C / methanol 5.1: 95 percent / cesium carbonate / dimethylformamide / 2 h With 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, hydrogen, caesium carbonate, triethylamine, (2R,3S)-(-)-di-O-benzoyl tartaric acid, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethylformamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys

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O 13 C O

13C

H C

C H

O 13 C

NH 2

13CH

H C

13CH

HCl

13 13

C H

Rx-ID: 38014824 View in Reaxys 77/408 Yield

Conditions & References

58 %

Stage 1: in methanol, ethanol, Time= 2h, Molecular sieve Stage 2: With methanol, sodium tetrahydroborate in ethanol Stage 3: With hydrogenchloride in diethyl ether, pH= 4 Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

N H

Rx-ID: 1835356 View in Reaxys 78/408 Yield

Conditions & References

31 %

With hydroxylamine, sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys With hydroxylamine hydrochloride, sodium cyanoborohydride in methanol, Time= 72h, Ambient temperature De Boer; Tan; Gorter; Van de Wal; Kettenes-van den Bosch; De Bruijn; Maes; Journal of Mass Spectrometry; vol. 32; nb. 11; (1997); p. 1236 - 1246 View in Reaxys Reaction Steps: 2 1: 51 percent / hydroxylamine hydrochloride, pyridine / ethanol / 2 h / Heating 2: NaBH3CN, aq. HCl / methanol / 72 h / Ambient temperature With pyridine, hydrogenchloride, hydroxylamine hydrochloride, sodium cyanoborohydride in methanol, ethanol Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys

N Z

NH 2

Rx-ID: 2661810 View in Reaxys 79/408 Yield

Conditions & References With lithium aluminium tetrahydride Rastogi, Shri Niwas; Kansal, V. K.; Bhaduri, A. P.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 22; nb. 3; (1983); p. 234 - 237 View in Reaxys Reaction Steps: 2 1: 70 percent / NaBH4 / methanol / 1 h / Ambient temperature 2: H2 / Raney Ni / ethanol / 2 h With sodium tetrahydroborate, hydrogen, nickel in methanol, ethanol Rastogi, Shri Niwas; Kansal, V. K.; Bhaduri, A. P.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 22; nb. 3; (1983); p. 234 - 237 View in Reaxys

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H N

N H

Rx-ID: 3626751 View in Reaxys 80/408 Yield

Conditions & References With lithium aluminium tetrahydride in diethyl ether, Time= 4h, Heating, Yield given Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys

H N

N H

Rx-ID: 3626752 View in Reaxys 81/408 Yield

N H

Rx-ID: 4188501 View in Reaxys 82/408 Yield 49 %, 47 %

Conditions & References With trifluorormethanesulfonic acid, 5A molecular sieve, chloranil, tetrabutylammonium perrhenate in dichloromethane, Time= 1.5h, Heating Kusama, Hiroyuki; Yamashita, Yuko; Narasaka, Koichi; Chemistry Letters; nb. 1; (1995); p. 5 - 6 View in Reaxys

O O

F F

H 2N

F F

Rx-ID: 4512931 View in Reaxys 83/408 Yield

Conditions & References With triethylamine in hexane, Time= 0.5h, T= 55 °C Kaufman, Melvin S.; Hatzis, Alexander C.; Stuart, John G.; Journal of Mass Spectrometry; vol. 31; nb. 8; (1996); p. 913 - 920 View in Reaxys

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O F

O F Cl F

O H 2N

H2 H

Rx-ID: 4517952 View in Reaxys 84/408 Yield

(+-)-2-<2-benzo<1,3>dioxol-5-yl-1-methyl-ethylamino>-1<3,4-dihydro-phenyl>-ethanone

N H

Rx-ID: 5559480 View in Reaxys 85/408 Yield

Conditions & References With ethanol, platinum, Hydrogenation Biel et al.; Journal of the American Chemical Society; vol. 76; (1954); p. 3149,3151 View in Reaxys

O O

N O

Rx-ID: 11971840 View in Reaxys 86/408 Yield

Conditions & References Reaction Steps: 4 1: 97 percent / H2 / Pd(OH)2/C / methanol / 6.5 h / 20 °C 2: 88 percent / LiBH4 / tetrahydrofuran; ethanol / 17 h / Heating 3: 66 percent / PPh3; I2; 1H-imidazole / CH2Cl2 / 3 h / 20 °C 4: 88 percent / N-Selectride(R) / tetrahydrofuran / 1.5 h / -5 °C With 1H-imidazole, lithium borohydride, hydrogen, iodine, Na-selectride, triphenylphosphine, palladium dihydroxide in tetrahydrofuran, methanol, ethanol, dichloromethane Manaka, Tomoyuki; Nagayama, Shin-Ichiro; Desadee, Wannaporn; Yajima, Naoki; Kumamoto, Takuya; Watanabe, Toshiko; Ishikawa, Tsutomu; Kawahata, Masatoshi; Yamaguchi, Kentaro; Helvetica Chimica Acta; vol. 90; nb. 1; (2007); p. 128 - 142 View in Reaxys

H N

O O

N H

Rx-ID: 14983668 View in Reaxys 87/408 Yield

Conditions & References Reaction Steps: 2 1: 95 percent / cesium carbonate / dimethylformamide / 2 h 2: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / Heating

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With lithium aluminium tetrahydride, caesium carbonate in tetrahydrofuran, N,N-dimethyl-formamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys Reaction Steps: 2 1: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With lithium aluminium tetrahydride, caesium carbonate in tetrahydrofuran, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H 2N

N H

Rx-ID: 18834146 View in Reaxys 88/408 Yield

Conditions & References Reaction Steps: 2 1: Heating 2: LAH / diethyl ether / 4 h / Heating With lithium aluminium tetrahydride in diethyl ether Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys

H 2N

N H

Rx-ID: 18834147 View in Reaxys 89/408 Yield

HO O

O O

N H

Rx-ID: 20472784 View in Reaxys 90/408 Yield

Conditions & References Reaction Steps: 2 1: 81 percent / Br2 / CHCl3 2: Et3N / tetrahydrofuran / 2 h / 25 °C With bromine, triethylamine in tetrahydrofuran, chloroform

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Grisar; Claxton; Bare; Dage; Cheng; Woodward; Journal of Medicinal Chemistry; vol. 24; nb. 3; (1981); p. 327 336 View in Reaxys

NH 2

Rx-ID: 20983864 View in Reaxys 91/408 Yield

Conditions & References Reaction Steps: 2 1: ammonium acetate / 1.) reflux, 8 h, 2.) RT, 60 h 2: LiAlH4, H2SO4 / tetrahydrofuran / Ambient temperature With ammonium acetate, lithium aluminium tetrahydride, sulfuric acid in tetrahydrofuran Glennon, Richard A.; Raghupathi, Reva; Bartyzel, Piotr; Teitler, Milt; Leonhardt, Sigrun; Journal of Medicinal Chemistry; vol. 35; nb. 4; (1992); p. 734 - 740 View in Reaxys

N Z

N H

Rx-ID: 21183686 View in Reaxys 92/408 Yield

Conditions & References Reaction Steps: 2 1: LAH 2: 90 percent / pyridine / 10 h / Ambient temperature With pyridine, lithium aluminium tetrahydride Rastogi, Shri Niwas; Kansal, V. K.; Bhaduri, A. P.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 22; nb. 3; (1983); p. 234 - 237 View in Reaxys Reaction Steps: 3 1: 70 percent / NaBH4 / methanol / 1 h / Ambient temperature 2: H2 / Raney Ni / ethanol / 2 h 3: 90 percent / pyridine / 10 h / Ambient temperature With pyridine, sodium tetrahydroborate, hydrogen, nickel in methanol, ethanol Rastogi, Shri Niwas; Kansal, V. K.; Bhaduri, A. P.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 22; nb. 3; (1983); p. 234 - 237 View in Reaxys

O O

N H

Rx-ID: 29474950 View in Reaxys 93/408 Yield

Conditions & References Stage 1: With hydrogenchloride in tetrahydrofuran, water, Time= 3h, T= 45 °C Stage 2: With potassium carbonate in water Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476 View in Reaxys

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H O

N H

H 2N

Rx-ID: 1835315 View in Reaxys 94/408 Yield

Conditions & References With hydrogen, W-2 Raney nickel, 1.) benzene, reflux, 7 h, 2.) ethanol, 50 psi, 24 h, Multistep reaction Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys

O O

NH 2

Rx-ID: 2568212 View in Reaxys 95/408 Yield

Conditions & References With hydrogen, nickel in ethanol, Time= 2h, Pressure (range begins): 2.5 <unit not given> Rastogi, Shri Niwas; Kansal, V. K.; Bhaduri, A. P.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 22; nb. 3; (1983); p. 234 - 237 View in Reaxys

N H

Rx-ID: 18512747 View in Reaxys 96/408 Yield

Conditions & References Reaction Steps: 2 1: NaBH3CN / methanol / 36 h / Ambient temperature; neutral pH 2: 58 percent / pyridine / 18 h / Ambient temperature With pyridine, sodium cyanoborohydride in methanol Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys Reaction Steps: 2 1: NaBH3CN, ammonium acetate / methanol / 36 h / Ambient temperature; neutral pH 2: 58 percent / pyridine / 18 h / Ambient temperature With pyridine, ammonium acetate, sodium cyanoborohydride in methanol Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys Reaction Steps: 2 1: Erhitzen des Reaktionsprodukts mit wss. Salzsaeure Elks; Hey; Journal of the Chemical Society; (1943); p. 15 View in Reaxys

O O

N H

Rx-ID: 21173079 View in Reaxys 97/408 Yield

Conditions & References Reaction Steps: 2

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1: H2 / Raney Ni / ethanol / 2 h 2: 90 percent / pyridine / 10 h / Ambient temperature With pyridine, hydrogen, nickel in ethanol Rastogi, Shri Niwas; Kansal, V. K.; Bhaduri, A. P.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 22; nb. 3; (1983); p. 234 - 237 View in Reaxys

N H

NH 2

Rx-ID: 22174376 View in Reaxys 98/408 Yield

Conditions & References Reaction Steps: 2 1: methanol; hydrazine hydrate 2: platinum; acetic acid; ethanol / 2942.03 Torr / Hydrogenation With methanol, ethanol, hydrazine hydrate, acetic acid, platinum Biel et al.; Journal of the American Chemical Society; vol. 81; (1959); p. 2805,2810, 2813 View in Reaxys

O 13 C O

13C

H C

C H

O 13 C

H 2N

13CH

13C

H C

C H

13C

HCl

Rx-ID: 38014825 View in Reaxys 99/408 Yield

Conditions & References

540 mg

Stage 1: in methanol, ethanol, Time= 2h, Molecular sieve Stage 2: With methanol, sodium tetrahydroborate in ethanol Stage 3: With hydrogenchloride in diethyl ether, isopropyl alcohol, T= 10 °C , pH= 4 Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

H N

O O

N H

Rx-ID: 38364357 View in Reaxys 100/408 Yield

Conditions & References With column LiChrospher 100 RP-18e, sulfated β-cyclodextrin in methanol, water, T= 20 °C , Reagent/catalyst Taschwer, Magdalena; Seidl, Yvonne; Mohr, Stefan; Schmid, Martin G.; Chirality; vol. 26; nb. 8; (2014); p. 411 418 View in Reaxys OH

O H 2N

O OH Cl

N H

Rx-ID: 150238 View in Reaxys 101/408 Yield

Conditions & References With ethanol Biel et al.; Journal of the American Chemical Society; vol. 76; (1954); p. 3149,3151 View in Reaxys

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O O

O Na +

H 2N

O–

O O

Rx-ID: 1802472 View in Reaxys 102/408 Yield

Conditions & References With sodium hydrogencarbonate in water, Time= 1h, T= 70 °C Frison, G.; Castagna, F.; Brusini, G.; Tedeschi, L.; Seraglia, R.; Traldi, P.; Organic Mass Spectrometry; vol. 27; nb. 11; (1992); p. 1284 - 1288 View in Reaxys

NH 2

Rx-ID: 1835352 View in Reaxys 103/408 Yield

Conditions & References

31 %

With ammonia, sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys With ammonium acetate, sodium cyanoborohydride in methanol, Time= 72h, Ambient temperature De Boer; Tan; Gorter; Van de Wal; Kettenes-van den Bosch; De Bruijn; Maes; Journal of Mass Spectrometry; vol. 32; nb. 11; (1997); p. 1236 - 1246 View in Reaxys

H N

NH 2

Rx-ID: 10388869 View in Reaxys 104/408 Yield

Conditions & References With NADPH, human liver microsomes in phosphate buffer, Time= 0.25h, T= 37 °C , pH= 7.4, Enzyme kinetics, Further Variations: Catalysts Kreth, Klaus-Peter; Kovar, Karl-Artur; Schwab, Matthias; Zanger, Ulrich M.; Biochemical Pharmacology; vol. 59; nb. 12; (2000); p. 1563 - 1571 View in Reaxys H N

NH 2

Rx-ID: 10415503 View in Reaxys 105/408 Yield

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H N

HO O

O OH

N H

Rx-ID: 29474958 View in Reaxys 106/408 Yield

Conditions & References

76 %

in ethanol, Time= 0.5h Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476 View in Reaxys

H N

O Cl

N H

Rx-ID: 37966350 View in Reaxys 107/408 Yield

Conditions & References Reaction Steps: 4 1: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 2: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 4: hydrogenchloride / diethyl ether With hydrogenchloride, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate in tetrahydrofuran, methanol, diethyl ether, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O O

N H

Rx-ID: 37966351 View in Reaxys 108/408 Yield

Conditions & References Reaction Steps: 2 1: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With lithium aluminium tetrahydride, caesium carbonate in tetrahydrofuran, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O O

O Cl O

N H

Rx-ID: 37966352 View in Reaxys 109/408 Yield

Conditions & References Reaction Steps: 3

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1: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 3: hydrogenchloride / diethyl ether With hydrogenchloride, lithium aluminium tetrahydride, caesium carbonate in tetrahydrofuran, diethyl ether, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

N H

Rx-ID: 37966354 View in Reaxys 110/408 Yield

Conditions & References Reaction Steps: 3 1: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 3: hydrogenchloride / diethyl ether With hydrogenchloride, lithium aluminium tetrahydride, caesium carbonate in tetrahydrofuran, diethyl ether, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O Cl

N H

Rx-ID: 37966356 View in Reaxys 111/408 Yield

Conditions & References Reaction Steps: 2 1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 2: hydrogenchloride / diethyl ether With hydrogenchloride, lithium aluminium tetrahydride in tetrahydrofuran, diethyl ether Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O O

N H

Rx-ID: 37966357 View in Reaxys 112/408 Yield

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View in Reaxys O

O N H

Rx-ID: 37966361 View in Reaxys 113/408 Yield

Conditions & References Reaction Steps: 8 1: ammonium acetate / 17 h / |Reflux 2: iron; iron(III) chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 3: titanium(IV) tetraethanolate / tetrahydrofuran / 5 h / |Reflux 4: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 5: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 6: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 7: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 8: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C With hydrogenchloride, dmap, iron(III) chloride, titanium(IV) tetraethanolate, sodium tetrahydroborate, palladium 10 on activated carbon, ammonium acetate, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4dioxane, methanol, ethanol, water, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O

O O

N H

Rx-ID: 37966362 View in Reaxys 114/408 Yield

Conditions & References Reaction Steps: 9 1: ammonium acetate / 17 h / |Reflux 2: iron; iron(III) chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 3: titanium(IV) tetraethanolate / tetrahydrofuran / 5 h / |Reflux 4: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 5: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 6: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 7: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 8: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 9: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With hydrogenchloride, dmap, iron(III) chloride, titanium(IV) tetraethanolate, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, ammonium acetate, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, ethanol, water, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

39/129

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O O

Cl O

N H

Rx-ID: 37966366 View in Reaxys 115/408 Yield

Conditions & References Reaction Steps: 10 1: ammonium acetate / 17 h / |Reflux 2: iron; iron(III) chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 3: titanium(IV) tetraethanolate / tetrahydrofuran / 5 h / |Reflux 4: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 5: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 6: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 7: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 8: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 9: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 10: hydrogenchloride / diethyl ether With hydrogenchloride, dmap, iron(III) chloride, titanium(IV) tetraethanolate, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, ammonium acetate, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, ethanol, water, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O

O O

Cl O

N H

Rx-ID: 37966367 View in Reaxys 116/408 Yield

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O E

N O

O N H

Rx-ID: 37966374 View in Reaxys 117/408 Yield

Conditions & References Reaction Steps: 7 1: iron; iron(III) chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 2: titanium(IV) tetraethanolate / tetrahydrofuran / 5 h / |Reflux 3: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 4: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 5: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 6: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 7: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C With hydrogenchloride, dmap, iron(III) chloride, titanium(IV) tetraethanolate, sodium tetrahydroborate, palladium 10 on activated carbon, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, ethanol, water, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O E

N O

O N H

Rx-ID: 37966375 View in Reaxys 118/408 Yield

O O

N O

O O

N H

Rx-ID: 37966376 View in Reaxys 119/408

41/129

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Yield

Conditions & References Reaction Steps: 8 1: iron; iron(III) chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 2: titanium(IV) tetraethanolate / tetrahydrofuran / 5 h / |Reflux 3: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 4: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 5: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 6: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 7: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 8: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With hydrogenchloride, dmap, iron(III) chloride, titanium(IV) tetraethanolate, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, ethanol, water, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O E

N O

N H

Rx-ID: 37966377 View in Reaxys 120/408 Yield

N O

O Cl O

N H

Rx-ID: 37966382 View in Reaxys 121/408 Yield

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5: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 6: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 7: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 8: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 9: hydrogenchloride / diethyl ether With hydrogenchloride, dmap, iron(III) chloride, titanium(IV) tetraethanolate, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, ethanol, water, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O N

Cl O

N H

Rx-ID: 37966383 View in Reaxys 122/408 Yield

Conditions & References Reaction Steps: 9 1: iron; iron(III) chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 2: titanium(IV) tetraethanolate / tetrahydrofuran / 5 h / |Reflux 3: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 4: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 5: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 6: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 7: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 8: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 9: hydrogenchloride / diethyl ether With hydrogenchloride, dmap, iron(III) chloride, titanium(IV) tetraethanolate, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, ethanol, water, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

S O

N H

Rx-ID: 37966390 View in Reaxys 123/408 Yield

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O S O

N H

Rx-ID: 37966391 View in Reaxys 124/408 Yield

Conditions & References Reaction Steps: 6 1: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 2: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 3: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 4: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 5: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With hydrogenchloride, dmap, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

O Cl

S O

N H

Rx-ID: 37966393 View in Reaxys 125/408 Yield

Conditions & References Reaction Steps: 7 1: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 2: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 3: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 4: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 5: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 7: hydrogenchloride / diethyl ether With hydrogenchloride, dmap, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

44/129

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N H

Rx-ID: 37966399 View in Reaxys 126/408 Yield

Conditions & References Reaction Steps: 5 1: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 2: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 3: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 4: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 5: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C With hydrogenchloride, dmap, sodium tetrahydroborate, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

O S O

N H

Rx-ID: 37966400 View in Reaxys 127/408 Yield

O Cl

S O

N H

Rx-ID: 37966401 View in Reaxys 128/408

45/129

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Yield

O O O

O N H

Rx-ID: 37966407 View in Reaxys 129/408 Yield

Conditions & References Reaction Steps: 6 1: titanium(IV) tetraethanolate / tetrahydrofuran / 5 h / |Reflux 2: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 3: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 4: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 5: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 6: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C With hydrogenchloride, dmap, titanium(IV) tetraethanolate, sodium tetrahydroborate, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

O O O

O O

O N H

Rx-ID: 37966408 View in Reaxys 130/408 Yield

46/129

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With hydrogenchloride, dmap, titanium(IV) tetraethanolate, sodium tetrahydroborate, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

O O

N H

Rx-ID: 37966409 View in Reaxys 131/408 Yield

Conditions & References Reaction Steps: 7 1: titanium(IV) tetraethanolate / tetrahydrofuran / 5 h / |Reflux 2: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 3: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 4: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 5: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 6: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 7: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With hydrogenchloride, dmap, titanium(IV) tetraethanolate, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

O O O

O O

N H

Rx-ID: 37966410 View in Reaxys 132/408 Yield

47/129

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O O

Cl O

N H

Rx-ID: 37966412 View in Reaxys 133/408 Yield

Conditions & References Reaction Steps: 8 1: titanium(IV) tetraethanolate / tetrahydrofuran / 5 h / |Reflux 2: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 3: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 4: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 5: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 6: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 7: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 8: hydrogenchloride / diethyl ether With hydrogenchloride, dmap, titanium(IV) tetraethanolate, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

O O O

O Cl O

N H

Rx-ID: 37966413 View in Reaxys 134/408 Yield

48/129

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H N

N H

Rx-ID: 37966423 View in Reaxys 135/408 Yield

Conditions & References Reaction Steps: 4 1: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 2: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 3: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 4: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C With hydrogenchloride, dmap, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O S O

N H

Rx-ID: 37966424 View in Reaxys 136/408 Yield

Conditions & References Reaction Steps: 5 1: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 2: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 3: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 4: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 5: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With hydrogenchloride, dmap, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O Cl

S O

N H

Rx-ID: 37966425 View in Reaxys 137/408 Yield

Conditions & References Reaction Steps: 6 1: hydrogenchloride / methanol; 1,4-dioxane / 20 °C

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2: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 3: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 4: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 5: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 6: hydrogenchloride / diethyl ether With hydrogenchloride, dmap, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

N H

Rx-ID: 37966430 View in Reaxys 138/408 Yield

H N

O S O

N H

Rx-ID: 37966431 View in Reaxys 139/408 Yield

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H N

O Cl

N H

Rx-ID: 37966432 View in Reaxys 140/408 Yield

Conditions & References Reaction Steps: 6 1: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 2: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 3: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 4: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 5: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 6: hydrogenchloride / diethyl ether With hydrogenchloride, dmap, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H NH 2

N H

Rx-ID: 37966435 View in Reaxys 141/408 Yield

Conditions & References Reaction Steps: 3 1: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 2: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 3: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C With dmap, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H NH 2

O O

N H

Rx-ID: 37966436 View in Reaxys 142/408 Yield

Conditions & References Reaction Steps: 4 1: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 2: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr

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3: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With dmap, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H NH 2

O Cl

N H

Rx-ID: 37966437 View in Reaxys 143/408 Yield

Conditions & References Reaction Steps: 5 1: dmap; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 2: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 3: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 5: hydrogenchloride / diethyl ether With hydrogenchloride, dmap, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, methanol, diethyl ether, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H NH 2

O Cl

N H

Rx-ID: 37966438 View in Reaxys 144/408 Yield

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H N

O N H

Rx-ID: 37966440 View in Reaxys 145/408 Yield

Conditions & References Reaction Steps: 2 1: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 2: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C With palladium 10 on activated carbon, hydrogen, caesium carbonate in methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O N H

Rx-ID: 37966441 View in Reaxys 146/408 Yield

Conditions & References Reaction Steps: 3 1: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 2: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate in tetrahydrofuran, methanol, N,N-dimethyl-formamide Llabrés, Salomé; García-Ratés, Sara; Cristóbal-Lecina, Edgar; Riera, Antoni; Borrell, José Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O O

O Cl O

N H

Rx-ID: 37966442 View in Reaxys 147/408 Yield

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H 2N

O N H

Rx-ID: 5050352 View in Reaxys 148/408 Yield 70 %

Conditions & References Time= 0.5h, T= 50 °C , Formylation Malmusi, Luca; Dukat, Malgorzata; Young, Richard; Teitler, Milt; Darmani, Nissar A.; Ahmad, Bashir; Smith, Carol; Glennon, Richard A.; Medicinal Chemistry Research; vol. 6; nb. 6; (1996); p. 412 - 426 View in Reaxys

rhodaninoic acid O

NH 2

Rx-ID: 13040270 View in Reaxys 149/408 Yield

Conditions & References Reaction Steps: 2 1: NH4OAc / Heating 2: LiAlH4 / diethyl ether With lithium aluminium tetrahydride, ammonium acetate in diethyl ether Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354 View in Reaxys

O O

rhodaninoic acid

N H

Rx-ID: 13040271 View in Reaxys 150/408 Yield

Conditions & References Reaction Steps: 3 1: NH4OAc / Heating 2: Iron; FeCl3; HCl / Heating 3: NaBH3CN / methanol With hydrogenchloride, ammonium acetate, iron(III) chloride, iron, sodium cyanoborohydride in methanol Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354 View in Reaxys

O O

rhodaninoic acid

N H

Rx-ID: 13040273 View in Reaxys 151/408 Yield

Conditions & References Reaction Steps: 3 1: NH4OAc / Heating 2: LiAlH4 / diethyl ether 3: Heating With lithium aluminium tetrahydride, ammonium acetate in diethyl ether

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Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354 View in Reaxys

O O

N H

Rx-ID: 13043127 View in Reaxys 152/408 Yield

Conditions & References Reaction Steps: 2 1: Iron; FeCl3; HCl / Heating 2: NaBH3CN / methanol With hydrogenchloride, iron(III) chloride, iron, sodium cyanoborohydride in methanol Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354 View in Reaxys

O O

N H

Rx-ID: 13043128 View in Reaxys 153/408 Yield

Conditions & References Reaction Steps: 2 1: LiAlH4 / diethyl ether 2: Heating With lithium aluminium tetrahydride in diethyl ether Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354 View in Reaxys

N H

Rx-ID: 18512748 View in Reaxys 154/408 Yield

Conditions & References Reaction Steps: 3 1: NaBH3CN / methanol / 36 h / Ambient temperature; neutral pH 2: 58 percent / pyridine / 18 h / Ambient temperature 3: LiAlH4 / tetrahydrofuran / 72 h / Heating With pyridine, lithium aluminium tetrahydride, sodium cyanoborohydride in tetrahydrofuran, methanol Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys Reaction Steps: 3 1: NaBH3CN, ammonium acetate / methanol / 36 h / Ambient temperature; neutral pH 2: 58 percent / pyridine / 18 h / Ambient temperature 3: LiAlH4 / tetrahydrofuran / 72 h / Heating With pyridine, ammonium acetate, lithium aluminium tetrahydride, sodium cyanoborohydride in tetrahydrofuran, methanol Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys

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O O

N H

H 2N

S O

S O O

Rx-ID: 23508395 View in Reaxys 155/408 Yield

Conditions & References 4B With sodium hydride in tetrahydrofuran, T= 20 °C Patent; DADE BEHRING INC.; WO2005/58864; (2005); (A1) English View in Reaxys

13C

C H

O 13 C

13CH

13C

H C

C H

NH 2

13C

HCl

Rx-ID: 38014808 View in Reaxys 156/408 Yield

Conditions & References Reaction Steps: 4 1.1: caesium carbonate / dimethyl sulfoxide / 2 h / 80 °C / |Inert atmosphere 2.1: N-Bromosuccinimide / chloroform / 2 h / |Reflux 3.1: tris-(o-tolyl)phosphine; tributyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 4.1: sodium cyanoborohydride; methanol; ammonium acetate / 20 °C / |Inert atmosphere 4.2: pH 4 With methanol, N-Bromosuccinimide, ammonium acetate, tributyltin methoxide, sodium cyanoborohydride, caesium carbonate, tris-(o-tolyl)phosphine, palladium dichloride in chloroform, dimethyl sulfoxide, toluene Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys Reaction Steps: 5 1.1: sodium hydride; N,N,N,N,N,N-hexamethylphosphoric triamide / 0.33 h / |Inert atmosphere 2.1: N-Bromosuccinimide / chloroform / 2 h / |Reflux 3.1: magnesium; bromine / tetrahydrofuran / 1 h / 55 °C 3.2: -20 - 20 °C 4.1: ammonium acetate; methylamine / 2 h / 80 °C 5.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 20 - 70 °C / |Inert atmosphere 5.2: pH 5 With N,N,N,N,N,N-hexamethylphosphoric triamide, N-Bromosuccinimide, ammonium acetate, bromine, sodium hydride, magnesium, sodium bis(2-methoxyethoxy)aluminium dihydride, methylamine in tetrahydrofuran, chloroform, toluene Patent; CHIRON AS; Johansen, Jon Eigill; Liu, Huiling; Karlsen, Morten; (15 pag.); US9435816; (2016); (B2) English View in Reaxys

O 13 C O

H C

C H

O 13 C

13C

H C

C H

NH 2

13C

HCl

Rx-ID: 38014817 View in Reaxys 157/408 Yield

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With methanol, N-Bromosuccinimide, ammonium acetate, tributyltin methoxide, sodium cyanoborohydride, tris-(otolyl)phosphine, palladium dichloride in chloroform, toluene Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys Reaction Steps: 4 1.1: N-Bromosuccinimide / chloroform / 2 h / |Reflux 2.1: magnesium; bromine / tetrahydrofuran / 1 h / 55 °C 2.2: -20 - 20 °C 3.1: ammonium acetate; methylamine / 2 h / 80 °C 4.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 20 - 70 °C / |Inert atmosphere 4.2: pH 5 With N-Bromosuccinimide, ammonium acetate, bromine, magnesium, sodium bis(2-methoxyethoxy)aluminium dihydride, methylamine in tetrahydrofuran, chloroform, toluene Patent; CHIRON AS; Johansen, Jon Eigill; Liu, Huiling; Karlsen, Morten; (15 pag.); US9435816; (2016); (B2) English View in Reaxys H 13 C Br O 13 13 C C O

13C

C H

O 13 C

13CH

13C

H C

C H

NH 2

13C

HCl

Rx-ID: 38014820 View in Reaxys 158/408 Yield

Conditions & References Reaction Steps: 2 1.1: tris-(o-tolyl)phosphine; tributyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 2.1: sodium cyanoborohydride; methanol; ammonium acetate / 20 °C / |Inert atmosphere 2.2: pH 4 With methanol, ammonium acetate, tributyltin methoxide, sodium cyanoborohydride, tris-(o-tolyl)phosphine, palladium dichloride in toluene Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys Reaction Steps: 3 1.1: magnesium; bromine / tetrahydrofuran / 1 h / 55 °C 1.2: -20 - 20 °C 2.1: ammonium acetate; methylamine / 2 h / 80 °C 3.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 20 - 70 °C / |Inert atmosphere 3.2: pH 5 With ammonium acetate, bromine, magnesium, sodium bis(2-methoxyethoxy)aluminium dihydride, methylamine in tetrahydrofuran, toluene Patent; CHIRON AS; Johansen, Jon Eigill; Liu, Huiling; Karlsen, Morten; (15 pag.); US9435816; (2016); (B2) English View in Reaxys

O H 2N

N H

O OH

Rx-ID: 1802474 View in Reaxys 159/408 Yield 21 %

Conditions & References With hydrogenchloride in ethanol, Time= 12h, Heating Leclerc; Decker; Schwartz; Arzneimittel-Forschung/Drug Research; vol. 35; nb. 9; (1985); p. 1357 - 1367 View in Reaxys

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NH 2

N H

Rx-ID: 1835338 View in Reaxys 160/408 Yield

Conditions & References

68 %

With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys

O O

H 2N

N H

Rx-ID: 1835347 View in Reaxys 161/408 Yield

Conditions & References

72 %

With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys

N H

Rx-ID: 1978664 View in Reaxys 162/408 Yield

Conditions & References With hydrogenchloride, sodium cyanoborohydride in methanol, Time= 72h, Ambient temperature Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys

H N

N H

Rx-ID: 2078501 View in Reaxys 163/408 Yield

Conditions & References With lithium aluminium tetrahydride in tetrahydrofuran, Time= 72h, Heating Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys

H 2N

N H

Rx-ID: 18512197 View in Reaxys 164/408 Yield

Conditions & References Reaction Steps: 2 1: 58 percent / pyridine / 18 h / Ambient temperature 2: LiAlH4 / tetrahydrofuran / 72 h / Heating With pyridine, lithium aluminium tetrahydride in tetrahydrofuran Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys

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O O

N H

Rx-ID: 18514992 View in Reaxys 165/408 Yield

Conditions & References Reaction Steps: 3 1: 87 percent / LiAlH4 2: 58 percent / pyridine / 18 h / Ambient temperature 3: LiAlH4 / tetrahydrofuran / 72 h / Heating With pyridine, lithium aluminium tetrahydride in tetrahydrofuran Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys

O O

H 2N

N H

Rx-ID: 1835317 View in Reaxys 166/408 Yield

Conditions & References With sodium cyanoborohydride in methanol, Time= 36h, Ambient temperature, pH neutral (12N HCl) Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys

O O

O Cl NH 2

N H

Rx-ID: 1835318 View in Reaxys 167/408 Yield

O O

NH 2Cl

H O

N H

Rx-ID: 1835319 View in Reaxys 168/408 Yield

H 2N O

N H

Rx-ID: 1835320 View in Reaxys 169/408 Yield

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O O

NH 2Cl

N H

Rx-ID: 1835322 View in Reaxys 170/408 Yield

O O

NH 2 Cl

N H

Rx-ID: 1835323 View in Reaxys 171/408 Yield

O O

Cl O

N H

H 2N

Rx-ID: 1835324 View in Reaxys 172/408 Yield

O O

NH 2 Cl

N H

Rx-ID: 1835326 View in Reaxys 173/408 Yield

H 2N O

Cl N H

H O

N H

H N

Rx-ID: 1835327 View in Reaxys 174/408 Yield

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O O

Cl NH 2

H O

N H

Rx-ID: 1835328 View in Reaxys 175/408 Yield

O O

H 2N

N H

Rx-ID: 1835329 View in Reaxys 176/408 Yield

O O

H 2N

N H

Rx-ID: 1835330 View in Reaxys 177/408 Yield

NH 2 O

N H

Rx-ID: 1835331 View in Reaxys 178/408 Yield 64 %

Conditions & References With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys

NH 2 Cl

N H

Rx-ID: 1835332 View in Reaxys 179/408 Yield

O O

Cl NH 2

N H

Rx-ID: 1835333 View in Reaxys 180/408

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Yield

O O

H 2N

H O

N H

Rx-ID: 1835334 View in Reaxys 181/408 Yield

Cl O

H O

H 2N

N H

Rx-ID: 1835335 View in Reaxys 182/408 Yield

O O

H 2N

N H

Rx-ID: 1835337 View in Reaxys 183/408 Yield

O O

H 2N

N H

Rx-ID: 1835353 View in Reaxys 184/408 Yield

Conditions & References With ammonium acetate, sodium cyanoborohydride in methanol, Time= 36h, Ambient temperature, neutral pH Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys

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O O F F

F O

H 2N

O F

HN F

F F

Rx-ID: 4512932 View in Reaxys 185/408 Yield

Conditions & References in ethyl acetate, Time= 0.333333h, T= 70 °C Kaufman, Melvin S.; Hatzis, Alexander C.; Stuart, John G.; Journal of Mass Spectrometry; vol. 31; nb. 8; (1996); p. 913 - 920 View in Reaxys

O F 2

O H 2N

F O

F F F O

F 2H 2H

F F

O F NH

F F

Rx-ID: 4552976 View in Reaxys 186/408 Yield

O O

N NH O

Rx-ID: 11948786 View in Reaxys 187/408 Yield

Conditions & References Reaction Steps: 2 1: 66 percent / PPh3; I2; 1H-imidazole / CH2Cl2 / 3 h / 20 °C 2: 88 percent / N-Selectride(R) / tetrahydrofuran / 1.5 h / -5 °C With 1H-imidazole, iodine, Na-selectride, triphenylphosphine in tetrahydrofuran, dichloromethane Manaka, Tomoyuki; Nagayama, Shin-Ichiro; Desadee, Wannaporn; Yajima, Naoki; Kumamoto, Takuya; Watanabe, Toshiko; Ishikawa, Tsutomu; Kawahata, Masatoshi; Yamaguchi, Kentaro; Helvetica Chimica Acta; vol. 90; nb. 1; (2007); p. 128 - 142 View in Reaxys

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O O

N O

NH O

Rx-ID: 11949377 View in Reaxys 188/408 Yield

Conditions & References Reaction Steps: 3 1: 88 percent / LiBH4 / tetrahydrofuran; ethanol / 17 h / Heating 2: 66 percent / PPh3; I2; 1H-imidazole / CH2Cl2 / 3 h / 20 °C 3: 88 percent / N-Selectride(R) / tetrahydrofuran / 1.5 h / -5 °C With 1H-imidazole, lithium borohydride, iodine, Na-selectride, triphenylphosphine in tetrahydrofuran, ethanol, dichloromethane Manaka, Tomoyuki; Nagayama, Shin-Ichiro; Desadee, Wannaporn; Yajima, Naoki; Kumamoto, Takuya; Watanabe, Toshiko; Ishikawa, Tsutomu; Kawahata, Masatoshi; Yamaguchi, Kentaro; Helvetica Chimica Acta; vol. 90; nb. 1; (2007); p. 128 - 142 View in Reaxys

H 13C 13CH HO

13C

13CH

H 13C 13CH

O 13 C O

13C

H C

C H

NH 2

13C

HCl

Rx-ID: 38014773 View in Reaxys 189/408 Yield

Conditions & References Reaction Steps: 6 1.1: magnesium methanolate / toluene / 40 - 75 °C / |Inert atmosphere 1.2: 95 - 100 °C 2.1: sodium hydroxide; dihydrogen peroxide / water / 30 - 40 °C / |Inert atmosphere 3.1: caesium carbonate / dimethyl sulfoxide / 2 h / 80 °C / |Inert atmosphere 4.1: N-Bromosuccinimide / chloroform / 2 h / |Reflux 5.1: tris-(o-tolyl)phosphine; tributyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 6.1: sodium cyanoborohydride; methanol; ammonium acetate / 20 °C / |Inert atmosphere 6.2: pH 4 With methanol, N-Bromosuccinimide, ammonium acetate, dihydrogen peroxide, tributyltin methoxide, sodium cyanoborohydride, caesium carbonate, magnesium methanolate, tris-(o-tolyl)phosphine, sodium hydroxide, palladium dichloride in chloroform, water, dimethyl sulfoxide, toluene, 2.1: |Dakin Phenol Oxidation Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

H 13C 13CH HO 13C

13CH

H 13C 13CH

O 13 C O

13C

H C

C H

13C

HCl

Rx-ID: 38014774 View in Reaxys 190/408 Yield

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With N-Bromosuccinimide, dihydrogen peroxide, tributyltin methoxide, caesium carbonate, magnesium methanolate, tris-(o-tolyl)phosphine, sodium hydroxide, palladium dichloride in methanol, ethanol, chloroform, water, dimethyl sulfoxide, toluene, 2.1: |Dakin Phenol Oxidation Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

H 13C 13CH 13CH HO 13C H 13C 13CH

O 13 C O

H C

13CH

HCl

13 13

C H

Rx-ID: 38014775 View in Reaxys 191/408 Yield

Conditions & References Reaction Steps: 6 1.1: magnesium methanolate / toluene / 40 - 75 °C / |Inert atmosphere 1.2: 95 - 100 °C 2.1: sodium hydroxide; dihydrogen peroxide / water / 30 - 40 °C / |Inert atmosphere 3.1: caesium carbonate / dimethyl sulfoxide / 2 h / 80 °C / |Inert atmosphere 4.1: N-Bromosuccinimide / chloroform / 2 h / |Reflux 5.1: tris-(o-tolyl)phosphine; tributyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 6.1: ethanol; methanol / 2 h / |Molecular sieve 6.3: pH 4 With N-Bromosuccinimide, dihydrogen peroxide, tributyltin methoxide, caesium carbonate, magnesium methanolate, tris-(o-tolyl)phosphine, sodium hydroxide, palladium dichloride in methanol, ethanol, chloroform, water, dimethyl sulfoxide, toluene, 2.1: |Dakin Phenol Oxidation Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys H C

H 13C H 13C

13C

O 13 C O

13C

H C

C H

NH 2

13C

HCl

Rx-ID: 38014803 View in Reaxys 192/408 Yield

Conditions & References Reaction Steps: 5 1.1: sodium hydroxide; dihydrogen peroxide / water / 30 - 40 °C / |Inert atmosphere 2.1: caesium carbonate / dimethyl sulfoxide / 2 h / 80 °C / |Inert atmosphere 3.1: N-Bromosuccinimide / chloroform / 2 h / |Reflux 4.1: tris-(o-tolyl)phosphine; tributyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 5.1: sodium cyanoborohydride; methanol; ammonium acetate / 20 °C / |Inert atmosphere 5.2: pH 4 With methanol, N-Bromosuccinimide, ammonium acetate, dihydrogen peroxide, tributyltin methoxide, sodium cyanoborohydride, caesium carbonate, tris-(o-tolyl)phosphine, sodium hydroxide, palladium dichloride in chloroform, water, dimethyl sulfoxide, toluene, 1.1: |Dakin Phenol Oxidation Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys H C

H 13C H 13C

13C

O 13 C O

13C

H C

C H

13C

HCl

Rx-ID: 38014804 View in Reaxys 193/408 Yield

Conditions & References Reaction Steps: 5

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1.1: sodium hydroxide; dihydrogen peroxide / water / 30 - 40 °C / |Inert atmosphere 2.1: caesium carbonate / dimethyl sulfoxide / 2 h / 80 °C / |Inert atmosphere 3.1: N-Bromosuccinimide / chloroform / 2 h / |Reflux 4.1: tris-(o-tolyl)phosphine; tributyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 5.1: ethanol; methanol / 2 h / |Molecular sieve 5.3: 10 °C / pH 4 With N-Bromosuccinimide, dihydrogen peroxide, tributyltin methoxide, caesium carbonate, tris-(o-tolyl)phosphine, sodium hydroxide, palladium dichloride in methanol, ethanol, chloroform, water, dimethyl sulfoxide, toluene, 1.1: |Dakin Phenol Oxidation Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys H C

H 13C H 13C

13C

O 13 C 13

13CH

HCl

H C

13C

C H

Rx-ID: 38014805 View in Reaxys 194/408 Yield

Conditions & References Reaction Steps: 5 1.1: sodium hydroxide; dihydrogen peroxide / water / 30 - 40 °C / |Inert atmosphere 2.1: caesium carbonate / dimethyl sulfoxide / 2 h / 80 °C / |Inert atmosphere 3.1: N-Bromosuccinimide / chloroform / 2 h / |Reflux 4.1: tris-(o-tolyl)phosphine; tributyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 5.1: ethanol; methanol / 2 h / |Molecular sieve 5.3: pH 4 With N-Bromosuccinimide, dihydrogen peroxide, tributyltin methoxide, caesium carbonate, tris-(o-tolyl)phosphine, sodium hydroxide, palladium dichloride in methanol, ethanol, chloroform, water, dimethyl sulfoxide, toluene, 1.1: |Dakin Phenol Oxidation Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

13C 13C

13C

13CH

O 13 C

13CH

13C

H C

C H

13C

HCl

Rx-ID: 38014809 View in Reaxys 195/408 Yield

13C 13C

13C

13CH

O 13 C

13CH

H C

13CH

HCl

13 13

C H

Rx-ID: 38014810 View in Reaxys 196/408

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Yield

O 13 C O

13C

O 13 C

13CH

13C

H C

C H

13C

HCl

Rx-ID: 38014818 View in Reaxys 197/408 Yield

Conditions & References Reaction Steps: 3 1.1: N-Bromosuccinimide / chloroform / 2 h / |Reflux 2.1: tris-(o-tolyl)phosphine; tributyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 3.1: ethanol; methanol / 2 h / |Molecular sieve 3.3: 10 °C / pH 4 With N-Bromosuccinimide, tributyltin methoxide, tris-(o-tolyl)phosphine, palladium dichloride in methanol, ethanol, chloroform, toluene Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

O 13 C O

13C

H C

13C

13CH

O 13 C

13CH

H C

13CH

HCl

C H

Rx-ID: 38014819 View in Reaxys 198/408 Yield

Conditions & References Reaction Steps: 3 1.1: N-Bromosuccinimide / chloroform / 2 h / |Reflux 2.1: tris-(o-tolyl)phosphine; tributyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 3.1: ethanol; methanol / 2 h / |Molecular sieve 3.3: pH 4 With N-Bromosuccinimide, tributyltin methoxide, tris-(o-tolyl)phosphine, palladium dichloride in methanol, ethanol, chloroform, toluene Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

H 13 C Br O 13 13 C C O

13C

C H

13CH

O 13 C O

13C

H C

C H

13C

HCl

Rx-ID: 38014821 View in Reaxys 199/408 Yield

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With tributyltin methoxide, tris-(o-tolyl)phosphine, palladium dichloride in methanol, ethanol, toluene Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

H 13 C Br O 13 13 C C O

13C

C H

O 13 C

13CH

H C

13CH

HCl

13 13

C H

Rx-ID: 38014822 View in Reaxys 200/408 Yield

Conditions & References Reaction Steps: 2 1.1: tris-(o-tolyl)phosphine; tributyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 2.1: ethanol; methanol / 2 h / |Molecular sieve 2.3: pH 4 With tributyltin methoxide, tris-(o-tolyl)phosphine, palladium dichloride in methanol, ethanol, toluene Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

NH 2

Rx-ID: 132175 View in Reaxys 201/408 Yield

Conditions & References With hydrogen bromide, T= 0 °C , Erhitzen des Reaktionsprodukts mit konz. Ammoniak auf 120grad Patent; Merck; DE274350; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 12; p. 768 View in Reaxys

N H

Rx-ID: 132179 View in Reaxys 202/408 Yield

Conditions & References With hydrogen bromide, T= 0 °C , Erhitzen des Reaktionsprodukts mit alkoh. Methylamin-Loesung auf 130grad Patent; Merck; DE274350; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 12; p. 768 View in Reaxys

O O

OH H 2N

N HO

S OO

H 2N

N H

Rx-ID: 1835336 View in Reaxys 203/408 Yield

Conditions & References With sodium cyanoborohydride in methanol, Time= 36h, Ambient temperature, neutral pH Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys

O O

NH 2

O O

N H

Rx-ID: 1835342 View in Reaxys 204/408

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Yield

Conditions & References

52 %

With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys

–

Na +

H 2N

NH 2

H N H

Rx-ID: 2320432 View in Reaxys 205/408 Yield

Conditions & References in water, Time= 2h, T= 50 °C , 2 h addition at 50 deg C, Yield given Kienzle; Bounameaux; Minder; Muggli; Helvetica Chimica Acta; vol. 69; nb. 7; (1986); p. 1671 - 1680 View in Reaxys O

H N

H 2N

Cl O

NH 2

N H

F OH

Rx-ID: 3487806 View in Reaxys 206/408 Yield

Conditions & References With sodium tetrahydroborate in isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys O

H N

H 2N

Br O

NH 2

N H

F OH

Rx-ID: 3487807 View in Reaxys 207/408 Yield

Conditions & References With sodium tetrahydroborate in isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys O

H N

N O NH 2

O O

H 2N

O N

N H

Cl OH

Rx-ID: 3488770 View in Reaxys 208/408 Yield

Conditions & References With sodium tetrahydroborate in isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

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O O

H N

O HN

H 2N

N HO

NH 2

Rx-ID: 3488859 View in Reaxys 209/408 Yield

Conditions & References With sodium tetrahydroborate in isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

O O O Cl

H N

O O

H 2N F

F F

F NH 2 Cl

Rx-ID: 3490431 View in Reaxys 210/408 Yield

Conditions & References With sodium tetrahydroborate in isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

O H 11 3 C

H 2N

N H

11CH

Rx-ID: 4818733 View in Reaxys 211/408 Yield

Conditions & References in acetonitrile, Time= 0.333333h, T= 120 °C Solbach, M.; Guendisch, D.; Wuellner, U.; Blocher, A.; Kovar, K.-A.; Machulla, H.-J.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 40; (1997); p. 522 - 524 View in Reaxys Br

H 2N

NH 2

N H

F OH

Rx-ID: 19188697 View in Reaxys 212/408 Yield

Conditions & References Reaction Steps: 2 1: propan-2-ol 2: NaBH4 / propan-2-ol With sodium tetrahydroborate in isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624

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View in Reaxys Cl

H 2N

NH 2

N H

F OH

Rx-ID: 19188698 View in Reaxys 213/408 Yield

H 2N

NH 2

N H

Cl OH

Rx-ID: 19188699 View in Reaxys 214/408 Yield

O O

O HN

H 2N

N HO NH 2

Rx-ID: 19188700 View in Reaxys 215/408 Yield

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O O

O H 2N

F F

F NH 2 Cl

Rx-ID: 19188701 View in Reaxys 216/408 Yield

H 2N

NH 2

N H

F O

Rx-ID: 19188806 View in Reaxys 217/408 Yield

Conditions & References Reaction Steps: 10 1: 76 percent / I2, NaHCO3 / H2O / 3 h / 60 °C 2: 88 percent / pyridine / CHCl3 / 1.) room temp., 0.5 h, 2.) 50-60 deg C, 2 h 3: 64 percent / hexamethylphosphoric acid triamide / 3 h / 150 °C 4: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 5: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 6: CrO3, conc. H2SO4 / acetone; H2O 7: 85 percent / conc. HCl / H2O / 1 h / Heating 8: Cl2 / acetic acid / 0.03 h / Ambient temperature 9: Br2 / acetic acid / Irradiation 10: propan-2-ol With pyridine, chromium(VI) oxide, hydrogenchloride, sulfuric acid, bromine, iodine, chlorine, sodium hydrogencarbonate, magnesium, tin(ll) chloride in N,N,N',N',N'',N''-hexamethylphosphoric triamide, diethyl ether, dichloromethane, chloroform, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

H 2N

NH 2

N H

F O

Rx-ID: 19188807 View in Reaxys 218/408 Yield

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8: Br2 / acetic acid 9: Br2 / acetic acid / Irradiation 10: propan-2-ol With pyridine, chromium(VI) oxide, hydrogenchloride, sulfuric acid, bromine, iodine, sodium hydrogencarbonate, magnesium, tin(ll) chloride in N,N,N',N',N'',N''-hexamethylphosphoric triamide, diethyl ether, dichloromethane, chloroform, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

H 2N

NH 2

N H

F OH

Rx-ID: 19188808 View in Reaxys 219/408 Yield

Conditions & References Reaction Steps: 11 1: 76 percent / I2, NaHCO3 / H2O / 3 h / 60 °C 2: 88 percent / pyridine / CHCl3 / 1.) room temp., 0.5 h, 2.) 50-60 deg C, 2 h 3: 64 percent / hexamethylphosphoric acid triamide / 3 h / 150 °C 4: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 5: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 6: CrO3, conc. H2SO4 / acetone; H2O 7: 85 percent / conc. HCl / H2O / 1 h / Heating 8: Br2 / acetic acid 9: Br2 / acetic acid / Irradiation 10: propan-2-ol 11: NaBH4 / propan-2-ol With pyridine, chromium(VI) oxide, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, bromine, iodine, sodium hydrogencarbonate, magnesium, tin(ll) chloride in N,N,N',N',N'',N''-hexamethylphosphoric triamide, diethyl ether, dichloromethane, chloroform, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl

H 2N

NH 2

N H

F OH

Rx-ID: 19188817 View in Reaxys 220/408 Yield

Conditions & References Reaction Steps: 11 1: 76 percent / I2, NaHCO3 / H2O / 3 h / 60 °C 2: 88 percent / pyridine / CHCl3 / 1.) room temp., 0.5 h, 2.) 50-60 deg C, 2 h 3: 64 percent / hexamethylphosphoric acid triamide / 3 h / 150 °C 4: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 5: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 6: CrO3, conc. H2SO4 / acetone; H2O 7: 85 percent / conc. HCl / H2O / 1 h / Heating 8: Cl2 / acetic acid / 0.03 h / Ambient temperature 9: Br2 / acetic acid / Irradiation 10: propan-2-ol 11: NaBH4 / propan-2-ol With pyridine, chromium(VI) oxide, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, bromine, iodine, chlorine, sodium hydrogencarbonate, magnesium, tin(ll) chloride in N,N,N',N',N'',N''-hexamethylphosphoric triamide, diethyl ether, dichloromethane, chloroform, water, acetic acid, isopropyl alcohol, acetone

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Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl H 2N

NH 2

O N H

F O

Rx-ID: 19193328 View in Reaxys 221/408 Yield

Conditions & References Reaction Steps: 9 1: 88 percent / pyridine / CHCl3 / 1.) room temp., 0.5 h, 2.) 50-60 deg C, 2 h 2: 64 percent / hexamethylphosphoric acid triamide / 3 h / 150 °C 3: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 4: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 5: CrO3, conc. H2SO4 / acetone; H2O 6: 85 percent / conc. HCl / H2O / 1 h / Heating 7: Cl2 / acetic acid / 0.03 h / Ambient temperature 8: Br2 / acetic acid / Irradiation 9: propan-2-ol With pyridine, chromium(VI) oxide, hydrogenchloride, sulfuric acid, bromine, chlorine, magnesium, tin(ll) chloride in N,N,N',N',N'',N''-hexamethylphosphoric triamide, diethyl ether, dichloromethane, chloroform, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

H 2N

NH 2

O N H

F O

Rx-ID: 19193329 View in Reaxys 222/408 Yield

Conditions & References Reaction Steps: 9 1: 88 percent / pyridine / CHCl3 / 1.) room temp., 0.5 h, 2.) 50-60 deg C, 2 h 2: 64 percent / hexamethylphosphoric acid triamide / 3 h / 150 °C 3: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 4: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 5: CrO3, conc. H2SO4 / acetone; H2O 6: 85 percent / conc. HCl / H2O / 1 h / Heating 7: Br2 / acetic acid 8: Br2 / acetic acid / Irradiation 9: propan-2-ol With pyridine, chromium(VI) oxide, hydrogenchloride, sulfuric acid, bromine, magnesium, tin(ll) chloride in N,N,N',N',N'',N''-hexamethylphosphoric triamide, diethyl ether, dichloromethane, chloroform, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

H 2N

I F

NH 2

O O

N H

F OH

Rx-ID: 19193330 View in Reaxys 223/408 Yield

Conditions & References Reaction Steps: 10 1: 88 percent / pyridine / CHCl3 / 1.) room temp., 0.5 h, 2.) 50-60 deg C, 2 h

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2: 64 percent / hexamethylphosphoric acid triamide / 3 h / 150 °C 3: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 4: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 5: CrO3, conc. H2SO4 / acetone; H2O 6: 85 percent / conc. HCl / H2O / 1 h / Heating 7: Br2 / acetic acid 8: Br2 / acetic acid / Irradiation 9: propan-2-ol 10: NaBH4 / propan-2-ol With pyridine, chromium(VI) oxide, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, bromine, magnesium, tin(ll) chloride in N,N,N',N',N'',N''-hexamethylphosphoric triamide, diethyl ether, dichloromethane, chloroform, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl H 2N

NH 2

N H

F OH

Rx-ID: 19193336 View in Reaxys 224/408 Yield

Conditions & References Reaction Steps: 10 1: 88 percent / pyridine / CHCl3 / 1.) room temp., 0.5 h, 2.) 50-60 deg C, 2 h 2: 64 percent / hexamethylphosphoric acid triamide / 3 h / 150 °C 3: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 4: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 5: CrO3, conc. H2SO4 / acetone; H2O 6: 85 percent / conc. HCl / H2O / 1 h / Heating 7: Cl2 / acetic acid / 0.03 h / Ambient temperature 8: Br2 / acetic acid / Irradiation 9: propan-2-ol 10: NaBH4 / propan-2-ol With pyridine, chromium(VI) oxide, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, bromine, chlorine, magnesium, tin(ll) chloride in N,N,N',N',N'',N''-hexamethylphosphoric triamide, diethyl ether, dichloromethane, chloroform, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys N

H 2N O N

NH 2

O O

N H

Cl O

Rx-ID: 19193459 View in Reaxys 225/408 Yield

Conditions & References Reaction Steps: 3 1: 51.5 percent / Cl2 / methanol; aq. acetic acid / 0.05 h / 7 °C 2: Br2 / acetic acid / Irradiation 3: propan-2-ol With bromine, chlorine in methanol, acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

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H 2N

NH 2

N H

Cl OH

Rx-ID: 19193460 View in Reaxys 226/408 Yield

Conditions & References Reaction Steps: 4 1: 51.5 percent / Cl2 / methanol; aq. acetic acid / 0.05 h / 7 °C 2: Br2 / acetic acid / Irradiation 3: propan-2-ol 4: NaBH4 / propan-2-ol With sodium tetrahydroborate, bromine, chlorine in methanol, acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

O O

NH 2 O

O NH 2

Rx-ID: 19193606 View in Reaxys 227/408 Yield

Conditions & References Reaction Steps: 3 1: 27 percent / dimethylformamide / 1.5 h / Heating 2: Br2 / acetic acid / Irradiation 3: propan-2-ol With bromine in acetic acid, N,N-dimethyl-formamide, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

O O

Br NH 2

HO NH 2

Rx-ID: 19193607 View in Reaxys 228/408 Yield

Conditions & References Reaction Steps: 4

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1: 27 percent / dimethylformamide / 1.5 h / Heating 2: Br2 / acetic acid / Irradiation 3: propan-2-ol 4: NaBH4 / propan-2-ol With sodium tetrahydroborate, bromine in acetic acid, N,N-dimethyl-formamide, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys N

NH 2 O

NH 2

O O

N H

Cl O

Rx-ID: 19202327 View in Reaxys 229/408 Yield

Conditions & References Reaction Steps: 5 1: I2, CaCO3 / methanol; H2O / 80 h / Ambient temperature 2: 52 percent / dimethylformamide / 1.5 h / Heating 3: 51.5 percent / Cl2 / methanol; aq. acetic acid / 0.05 h / 7 °C 4: Br2 / acetic acid / Irradiation 5: propan-2-ol With bromine, iodine, chlorine, calcium carbonate in methanol, water, acetic acid, N,N-dimethyl-formamide, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys N

NH 2 O

NH 2

O O

N H

Cl OH

Rx-ID: 19202331 View in Reaxys 230/408 Yield

Conditions & References Reaction Steps: 6 1: I2, CaCO3 / methanol; H2O / 80 h / Ambient temperature 2: 52 percent / dimethylformamide / 1.5 h / Heating 3: 51.5 percent / Cl2 / methanol; aq. acetic acid / 0.05 h / 7 °C 4: Br2 / acetic acid / Irradiation 5: propan-2-ol 6: NaBH4 / propan-2-ol With sodium tetrahydroborate, bromine, iodine, chlorine, calcium carbonate in methanol, water, acetic acid, N,N-dimethyl-formamide, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys N

I NH 2

NH 2 O

N H

Cl O

Rx-ID: 19206663 View in Reaxys 231/408 Yield

Conditions & References Reaction Steps: 4 1: 52 percent / dimethylformamide / 1.5 h / Heating 2: 51.5 percent / Cl2 / methanol; aq. acetic acid / 0.05 h / 7 °C

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3: Br2 / acetic acid / Irradiation 4: propan-2-ol With bromine, chlorine in methanol, acetic acid, N,N-dimethyl-formamide, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys N

I NH 2

NH 2 O

N H

Cl OH

Rx-ID: 19206664 View in Reaxys 232/408 Yield

Conditions & References Reaction Steps: 5 1: 52 percent / dimethylformamide / 1.5 h / Heating 2: 51.5 percent / Cl2 / methanol; aq. acetic acid / 0.05 h / 7 °C 3: Br2 / acetic acid / Irradiation 4: propan-2-ol 5: NaBH4 / propan-2-ol With sodium tetrahydroborate, bromine, chlorine in methanol, acetic acid, N,N-dimethyl-formamide, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl

NH 2

NH 2 O

N H

F O

Rx-ID: 19207277 View in Reaxys 233/408 Yield

Conditions & References Reaction Steps: 3 1: Cl2 / acetic acid / 0.03 h / Ambient temperature 2: Br2 / acetic acid / Irradiation 3: propan-2-ol With bromine, chlorine in acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

F NH 2 O

NH 2

O O

N H

F O

Rx-ID: 19207278 View in Reaxys 234/408 Yield

Conditions & References Reaction Steps: 3 1: Br2 / acetic acid 2: Br2 / acetic acid / Irradiation 3: propan-2-ol With bromine in acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

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NH 2

N H

F OH

Rx-ID: 19207279 View in Reaxys 235/408 Yield

Conditions & References Reaction Steps: 4 1: Br2 / acetic acid 2: Br2 / acetic acid / Irradiation 3: propan-2-ol 4: NaBH4 / propan-2-ol With sodium tetrahydroborate, bromine in acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl

NH 2

N H

F OH

Rx-ID: 19207285 View in Reaxys 236/408 Yield

Conditions & References Reaction Steps: 4 1: Cl2 / acetic acid / 0.03 h / Ambient temperature 2: Br2 / acetic acid / Irradiation 3: propan-2-ol 4: NaBH4 / propan-2-ol With sodium tetrahydroborate, bromine, chlorine in acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

H N

NH 2

N H

F O

Rx-ID: 19207829 View in Reaxys 237/408 Yield

Conditions & References Reaction Steps: 8 1: 64 percent / hexamethylphosphoric acid triamide / 3 h / 150 °C 2: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 3: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 4: CrO3, conc. H2SO4 / acetone; H2O 5: 85 percent / conc. HCl / H2O / 1 h / Heating 6: Cl2 / acetic acid / 0.03 h / Ambient temperature 7: Br2 / acetic acid / Irradiation 8: propan-2-ol With chromium(VI) oxide, hydrogenchloride, sulfuric acid, bromine, chlorine, magnesium, tin(ll) chloride in N,N,N',N',N'',N''-hexamethylphosphoric triamide, diethyl ether, dichloromethane, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

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H N

NH 2

N H

F O

Rx-ID: 19207830 View in Reaxys 238/408 Yield

Conditions & References Reaction Steps: 8 1: 64 percent / hexamethylphosphoric acid triamide / 3 h / 150 °C 2: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 3: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 4: CrO3, conc. H2SO4 / acetone; H2O 5: 85 percent / conc. HCl / H2O / 1 h / Heating 6: Br2 / acetic acid 7: Br2 / acetic acid / Irradiation 8: propan-2-ol With chromium(VI) oxide, hydrogenchloride, sulfuric acid, bromine, magnesium, tin(ll) chloride in N,N,N',N',N'',N''hexamethylphosphoric triamide, diethyl ether, dichloromethane, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

H N

NH 2

N H

F OH

Rx-ID: 19207831 View in Reaxys 239/408 Yield

Conditions & References Reaction Steps: 9 1: 64 percent / hexamethylphosphoric acid triamide / 3 h / 150 °C 2: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 3: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 4: CrO3, conc. H2SO4 / acetone; H2O 5: 85 percent / conc. HCl / H2O / 1 h / Heating 6: Br2 / acetic acid 7: Br2 / acetic acid / Irradiation 8: propan-2-ol 9: NaBH4 / propan-2-ol With chromium(VI) oxide, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, bromine, magnesium, tin(ll) chloride in N,N,N',N',N'',N''-hexamethylphosphoric triamide, diethyl ether, dichloromethane, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

H N

NH 2

N H

F OH

Rx-ID: 19207837 View in Reaxys 240/408 Yield

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7: Br2 / acetic acid / Irradiation 8: propan-2-ol 9: NaBH4 / propan-2-ol With chromium(VI) oxide, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, bromine, chlorine, magnesium, tin(ll) chloride in N,N,N',N',N'',N''-hexamethylphosphoric triamide, diethyl ether, dichloromethane, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl

NH 2

NH 2 O

O F

N H

F O

Rx-ID: 19208083 View in Reaxys 241/408 Yield

Conditions & References Reaction Steps: 2 1: Br2 / acetic acid / Irradiation 2: propan-2-ol With bromine in acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl

NH 2

NH 2 O

O F

N H

F OH

Rx-ID: 19208084 View in Reaxys 242/408 Yield

Conditions & References Reaction Steps: 3 1: Br2 / acetic acid / Irradiation 2: propan-2-ol 3: NaBH4 / propan-2-ol With sodium tetrahydroborate, bromine in acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

NH 2

NH 2 O

O F

N H

F O

Rx-ID: 19208134 View in Reaxys 243/408 Yield

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NH 2

NH 2 O

N H

F OH

Rx-ID: 19208135 View in Reaxys 244/408 Yield

NH 2

O HN

N H

F O

Rx-ID: 19208362 View in Reaxys 245/408 Yield

Conditions & References Reaction Steps: 7 1: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 2: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 3: CrO3, conc. H2SO4 / acetone; H2O 4: 85 percent / conc. HCl / H2O / 1 h / Heating 5: Cl2 / acetic acid / 0.03 h / Ambient temperature 6: Br2 / acetic acid / Irradiation 7: propan-2-ol With chromium(VI) oxide, hydrogenchloride, sulfuric acid, bromine, chlorine, magnesium, tin(ll) chloride in diethyl ether, dichloromethane, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

NH 2

O HN O

N H

F O

Rx-ID: 19208363 View in Reaxys 246/408 Yield

Conditions & References Reaction Steps: 7 1: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 2: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 3: CrO3, conc. H2SO4 / acetone; H2O 4: 85 percent / conc. HCl / H2O / 1 h / Heating 5: Br2 / acetic acid 6: Br2 / acetic acid / Irradiation 7: propan-2-ol With chromium(VI) oxide, hydrogenchloride, sulfuric acid, bromine, magnesium, tin(ll) chloride in diethyl ether, dichloromethane, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

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NH 2

O HN

N H

F OH

Rx-ID: 19208364 View in Reaxys 247/408 Yield

Conditions & References Reaction Steps: 8 1: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 2: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 3: CrO3, conc. H2SO4 / acetone; H2O 4: 85 percent / conc. HCl / H2O / 1 h / Heating 5: Br2 / acetic acid 6: Br2 / acetic acid / Irradiation 7: propan-2-ol 8: NaBH4 / propan-2-ol With chromium(VI) oxide, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, bromine, magnesium, tin(ll) chloride in diethyl ether, dichloromethane, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl

NH 2

O HN

N H

F OH

Rx-ID: 19208370 View in Reaxys 248/408 Yield

Conditions & References Reaction Steps: 8 1: 95 percent / SnCl2, HCl / diethyl ether; CH2Cl2 / 2 h 2: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 3: CrO3, conc. H2SO4 / acetone; H2O 4: 85 percent / conc. HCl / H2O / 1 h / Heating 5: Cl2 / acetic acid / 0.03 h / Ambient temperature 6: Br2 / acetic acid / Irradiation 7: propan-2-ol 8: NaBH4 / propan-2-ol With chromium(VI) oxide, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, bromine, chlorine, magnesium, tin(ll) chloride in diethyl ether, dichloromethane, water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl

NH 2

HN O

N H

F O

Rx-ID: 19208445 View in Reaxys 249/408 Yield

Conditions & References Reaction Steps: 6 1: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 2: CrO3, conc. H2SO4 / acetone; H2O 3: 85 percent / conc. HCl / H2O / 1 h / Heating 4: Cl2 / acetic acid / 0.03 h / Ambient temperature 5: Br2 / acetic acid / Irradiation 6: propan-2-ol With chromium(VI) oxide, hydrogenchloride, sulfuric acid, bromine, chlorine, magnesium in water, acetic acid, isopropyl alcohol, acetone

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Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

NH 2

HN O

N H

F O

Rx-ID: 19208446 View in Reaxys 250/408 Yield

Conditions & References Reaction Steps: 6 1: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 2: CrO3, conc. H2SO4 / acetone; H2O 3: 85 percent / conc. HCl / H2O / 1 h / Heating 4: Br2 / acetic acid 5: Br2 / acetic acid / Irradiation 6: propan-2-ol With chromium(VI) oxide, hydrogenchloride, sulfuric acid, bromine, magnesium in water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

NH 2

HN O

N H

F OH

Rx-ID: 19208447 View in Reaxys 251/408 Yield

Conditions & References Reaction Steps: 7 1: 1.) Mg / 1.) diethyl ether, 30 min, 2.) THF, diethyl ether, overnight, reflux 2: CrO3, conc. H2SO4 / acetone; H2O 3: 85 percent / conc. HCl / H2O / 1 h / Heating 4: Br2 / acetic acid 5: Br2 / acetic acid / Irradiation 6: propan-2-ol 7: NaBH4 / propan-2-ol With chromium(VI) oxide, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, bromine, magnesium in water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl

NH 2

HN O

N H

F OH

Rx-ID: 19208453 View in Reaxys 252/408 Yield

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With chromium(VI) oxide, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, bromine, chlorine, magnesium in water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl

NH 2

HN O

N H

F O

Rx-ID: 19208547 View in Reaxys 253/408 Yield

Conditions & References Reaction Steps: 5 1: CrO3, conc. H2SO4 / acetone; H2O 2: 85 percent / conc. HCl / H2O / 1 h / Heating 3: Cl2 / acetic acid / 0.03 h / Ambient temperature 4: Br2 / acetic acid / Irradiation 5: propan-2-ol With chromium(VI) oxide, hydrogenchloride, sulfuric acid, bromine, chlorine in water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

NH 2

HN O

N H

F O

Rx-ID: 19208548 View in Reaxys 254/408 Yield

Conditions & References Reaction Steps: 5 1: CrO3, conc. H2SO4 / acetone; H2O 2: 85 percent / conc. HCl / H2O / 1 h / Heating 3: Br2 / acetic acid 4: Br2 / acetic acid / Irradiation 5: propan-2-ol With chromium(VI) oxide, hydrogenchloride, sulfuric acid, bromine in water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

NH 2

HN O

N H

F OH

Rx-ID: 19208549 View in Reaxys 255/408 Yield

Conditions & References Reaction Steps: 6 1: CrO3, conc. H2SO4 / acetone; H2O 2: 85 percent / conc. HCl / H2O / 1 h / Heating 3: Br2 / acetic acid 4: Br2 / acetic acid / Irradiation 5: propan-2-ol 6: NaBH4 / propan-2-ol With chromium(VI) oxide, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, bromine in water, acetic acid, isopropyl alcohol, acetone

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Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl

NH 2

HN O

N H

F OH

Rx-ID: 19208555 View in Reaxys 256/408 Yield

Conditions & References Reaction Steps: 6 1: CrO3, conc. H2SO4 / acetone; H2O 2: 85 percent / conc. HCl / H2O / 1 h / Heating 3: Cl2 / acetic acid / 0.03 h / Ambient temperature 4: Br2 / acetic acid / Irradiation 5: propan-2-ol 6: NaBH4 / propan-2-ol With chromium(VI) oxide, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, bromine, chlorine in water, acetic acid, isopropyl alcohol, acetone Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl

NH 2

HN O

N H

F O

Rx-ID: 19208967 View in Reaxys 257/408 Yield

Conditions & References Reaction Steps: 4 1: 85 percent / conc. HCl / H2O / 1 h / Heating 2: Cl2 / acetic acid / 0.03 h / Ambient temperature 3: Br2 / acetic acid / Irradiation 4: propan-2-ol With hydrogenchloride, bromine, chlorine in water, acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

NH 2

HN O

N H

F O

Rx-ID: 19208968 View in Reaxys 258/408 Yield

Conditions & References Reaction Steps: 4 1: 85 percent / conc. HCl / H2O / 1 h / Heating 2: Br2 / acetic acid 3: Br2 / acetic acid / Irradiation 4: propan-2-ol With hydrogenchloride, bromine in water, acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

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NH 2

HN O

N H

F OH

Rx-ID: 19208969 View in Reaxys 259/408 Yield

Conditions & References Reaction Steps: 5 1: 85 percent / conc. HCl / H2O / 1 h / Heating 2: Br2 / acetic acid 3: Br2 / acetic acid / Irradiation 4: propan-2-ol 5: NaBH4 / propan-2-ol With hydrogenchloride, sodium tetrahydroborate, bromine in water, acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Cl

NH 2

HN O

N H

F OH

Rx-ID: 19208975 View in Reaxys 260/408 Yield

Conditions & References Reaction Steps: 5 1: 85 percent / conc. HCl / H2O / 1 h / Heating 2: Cl2 / acetic acid / 0.03 h / Ambient temperature 3: Br2 / acetic acid / Irradiation 4: propan-2-ol 5: NaBH4 / propan-2-ol With hydrogenchloride, sodium tetrahydroborate, bromine, chlorine in water, acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys N

Cl H 2N

NH 2

O O

N H

Cl O

Rx-ID: 19209169 View in Reaxys 261/408 Yield

Cl H 2N

NH 2

O N

N H

Cl OH

Rx-ID: 19209170 View in Reaxys 262/408 Yield

Conditions & References Reaction Steps: 3

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1: Br2 / acetic acid / Irradiation 2: propan-2-ol 3: NaBH4 / propan-2-ol With sodium tetrahydroborate, bromine in acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

O O

H 2N O

N N

O NH 2

Rx-ID: 19209422 View in Reaxys 263/408 Yield

O O

H 2N

O N

N HO NH 2

Rx-ID: 19209423 View in Reaxys 264/408 Yield

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NH 2

O NH 2

Br F

N H

F OH

Rx-ID: 19209710 View in Reaxys 265/408 Yield

NH 2

O NH 2

Br F

N H

F OH

Rx-ID: 19209720 View in Reaxys 266/408 Yield

NH 2

O NH 2

N H

Cl OH

Rx-ID: 19210434 View in Reaxys 267/408 Yield

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O O

Cl H 2N F

F O

F NH 2 Cl

Rx-ID: 19210751 View in Reaxys 268/408 Yield

Conditions & References Reaction Steps: 2 1: Br2 / acetic acid / 0.5 h / 60 - 65 °C / Irradiation 2: propan-2-ol With bromine in acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

O O

Cl H 2N F

F NH 2 Cl

Rx-ID: 19210755 View in Reaxys 269/408 Yield

Conditions & References Reaction Steps: 3 1: Br2 / acetic acid / 0.5 h / 60 - 65 °C / Irradiation 2: propan-2-ol 3: NaBH4 / propan-2-ol With sodium tetrahydroborate, bromine in acetic acid, isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

O O

N O NH 2

N N

HO NH 2

Rx-ID: 19211016 View in Reaxys 270/408 Yield

Conditions & References Reaction Steps: 2

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1: propan-2-ol 2: NaBH4 / propan-2-ol With sodium tetrahydroborate in isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

O O

Cl H 2N F

F F

F NH 2 Cl

Rx-ID: 19212036 View in Reaxys 271/408 Yield

K+

O –

N H

Rx-ID: 29474948 View in Reaxys 272/408 Yield

Conditions & References in tetrahydrofuran, tert-butyl alcohol, T= 20 °C , Cooling with ice Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476 View in Reaxys

O O

H 2N

N H

Rx-ID: 150251 View in Reaxys 273/408 Yield

Conditions & References Patent; Merck,E.; DE549967; (1930); View in Reaxys With sodium hydroxide Morimoto; Yakugaku Zasshi; vol. 72; (1952); p. 1952> 99; ; (1952); p. 11207 View in Reaxys With benzene Dobrowsky; Monatshefte fuer Chemie; vol. 82; (1951); p. 122,134 View in Reaxys

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O O

H 2N

O O

N H

Rx-ID: 1802480 View in Reaxys 274/408 Yield

Conditions & References With rabbit liver cytochrome P450IIB4, 1,2-dilauroylphosphatidylcholine, NADPH, NADPH-cytochrome P450 reductase, ascorbic acid powder in water, Time= 0.0833333h, T= 37 °C , other (methylenedioxy)phenyl compounds; also in the hydroxyl radical system (ferric chloride, EDTA, potassium phosphate buffer, pH 7.4); demethylenation reaction, Mechanism Fukuto; Kumagai; Cho; Journal of Medicinal Chemistry; vol. 34; nb. 9; (1991); p. 2871 - 2876 View in Reaxys

O O

NH 2

N H

Rx-ID: 1835339 View in Reaxys 275/408 Yield 35 %

Conditions & References With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys

O O

H 2N O

N H

Rx-ID: 1835345 View in Reaxys 276/408 Yield 39 %

Conditions & References With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys

O O

H 2N

N H

Rx-ID: 1835349 View in Reaxys 277/408 Yield 39 %

Conditions & References With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys

H 2N

O O

NH 2

Rx-ID: 1767860 View in Reaxys 278/408 Yield

Conditions & References With ammonium hydroxide, sodium hypochlorite, borane-THF, 1.) THF, 0 deg C to r.t., 1 h, 2.) 0 deg C, 15 min, Yield given. Multistep reaction. Yields of byproduct given Kabalka, George W.; Sastry, Kunda A. R.; McCollum, Gary W.; Yoshioka, Hiroaki; Journal of Organic Chemistry; vol. 46; nb. 21; (1981); p. 4296 - 4298 View in Reaxys

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H 2N O

N H

Rx-ID: 1835311 View in Reaxys 279/408 Yield

Conditions & References

25 %

With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys

NH 2 O

N H

Rx-ID: 1835312 View in Reaxys 280/408 Yield 28 %

Conditions & References With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys

O O

NH 2

N H

Rx-ID: 1835343 View in Reaxys 281/408 Yield 26 %

Conditions & References With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys

O O

H 2N

O HN

O O

Rx-ID: 150233 View in Reaxys 282/408 Yield

Conditions & References With benzene Dobrowsky; Monatshefte fuer Chemie; vol. 82; (1951); p. 122,134 View in Reaxys With sodium hydroxide Morimoto; Yakugaku Zasshi; vol. 72; (1952); p. 1952> 102; ; (1952); p. 11207 View in Reaxys

O O

H 2N

N H

Rx-ID: 1835348 View in Reaxys 283/408

93/129

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Yield 15 %

Conditions & References With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys

O O

N H

Rx-ID: 18514991 View in Reaxys 284/408 Yield

Conditions & References Reaction Steps: 2 1: 87 percent / LiAlH4 2: 58 percent / pyridine / 18 h / Ambient temperature With pyridine, lithium aluminium tetrahydride Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys

oxime of 3.4-methylenedioxy-phenylacetone O

NH 2

Rx-ID: 5446370 View in Reaxys 285/408 Yield

Conditions & References With sodium amalgam, acetic acid Mannich; Jacobsohn; Chemische Berichte; vol. 43; (1910); p. 193 View in Reaxys O O

O O

Rx-ID: 22248223 View in Reaxys 286/408 Yield

Conditions & References Reaction Steps: 2 1: lithium alanate; diethyl ether 2: 140 °C With lithium aluminium tetrahydride, diethyl ether Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys Reaction Steps: 2 1: lithium alanate; diethyl ether 2: benzene With lithium aluminium tetrahydride, diethyl ether, benzene Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

94/129

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O O

N H

Rx-ID: 22248225 View in Reaxys 287/408 Yield

Conditions & References Reaction Steps: 2 1: lithium alanate; diethyl ether With lithium aluminium tetrahydride, diethyl ether Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys Reaction Steps: 2 1: lithium alanate; diethyl ether With lithium aluminium tetrahydride, diethyl ether Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

H 2N

N H

Rx-ID: 150227 View in Reaxys 288/408 Yield

Conditions & References T= 200 °C Dobrowsky; Monatshefte fuer Chemie; vol. 82; (1951); p. 122,134 View in Reaxys

O O H 2N

N H

Rx-ID: 150235 View in Reaxys 289/408 Yield

Conditions & References With decalin Dobrowsky; Monatshefte fuer Chemie; vol. 82; (1951); p. 122,134 View in Reaxys

O H 2N

N H

Rx-ID: 150254 View in Reaxys 290/408 Yield

Conditions & References With benzene Rosenmund; Chem. Zentralbl.; vol. 90; nb. I; (1919); p. 953 View in Reaxys Patent; Merck; DE273323; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 12; p. 761 View in Reaxys

95/129

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O O

O H 2N

O Cl

Cl O

O O

Rx-ID: 150255 View in Reaxys 291/408 Yield

Conditions & References With sodium hydroxide, benzene Dobrowsky; Monatshefte fuer Chemie; vol. 86; (1955); p. 27 View in Reaxys

O O H 2N

N H

Rx-ID: 150259 View in Reaxys 292/408 Yield

Conditions & References With alkaline solution Dobrowsky; Monatshefte fuer Chemie; vol. 82; (1951); p. 122,134 View in Reaxys

O O H 2N

O N

N H

Rx-ID: 150261 View in Reaxys 293/408 Yield

Conditions & References With potassium carbonate, acetone Morimoto; Yakugaku Zasshi; vol. 72; (1952); p. 1952> 95, 97; ; (1952); p. 582 View in Reaxys With diethyl ether, ethyl acetate Morimoto; Yakugaku Zasshi; vol. 72; (1952); p. 1952> 95, 97; ; (1952); p. 582 View in Reaxys

O O H 2N

N H

Rx-ID: 150262 View in Reaxys 294/408 Yield

Conditions & References T= 180 °C

96/129

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Dobrowsky; Monatshefte fuer Chemie; vol. 82; (1951); p. 122,134 View in Reaxys

NH 2

Rx-ID: 265966 View in Reaxys 295/408 Yield

Conditions & References With ethanol, sodium Fujisawa; Deguchi; Yakugaku Zasshi; vol. 74; (1954); p. 977,979; ; (1955); p. 10959 View in Reaxys

O H 2N

N H

Rx-ID: 1918706 View in Reaxys 296/408 Yield

Conditions & References Heating, Yield given Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys

O H 2N

N H

Rx-ID: 1918707 View in Reaxys 297/408 Yield

Conditions & References Heating, Yield given Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys O O

quinoline-8-carbonyl chloride-hydrochloride H 2N

O N

Rx-ID: 5548818 View in Reaxys 298/408 Yield

Conditions & References With benzene Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

97/129

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O O

quinoline-4-carbonyl chloride-hydrochloride

H 2N

Rx-ID: 5548821 View in Reaxys 299/408 Yield

Conditions & References With benzene Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

quinoline-3-carbonyl chloride-hydrochloride

N H

H 2N

Rx-ID: 5548901 View in Reaxys 300/408 Yield

Conditions & References With benzene Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

O O O

quinoline-6-carbonyl chloride-hydrochloride O

H 2N

O N

Rx-ID: 5548902 View in Reaxys 301/408 Yield

Conditions & References With benzene Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

3-benzoyloxy-benzoyl chloride O

H 2N

O O

O N H

Rx-ID: 5573403 View in Reaxys 302/408 Yield

Conditions & References With diethyl ether, water, sodium hydrogencarbonate Fujisawa; Deguchi; Yakugaku Zasshi; vol. 74; (1954); p. 977,979; ; (1955); p. 10959 View in Reaxys

98/129

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N H

Rx-ID: 22238794 View in Reaxys 303/408 Yield

Conditions & References Reaction Steps: 2 1: thionyl chloride 2: diethyl ether; aq. NaOH solution With sodium hydroxide, thionyl chloride, diethyl ether Kametani; Inagaki; Yakugaku Zasshi; vol. 74; (1954); p. 1040; ; (1955); p. 11 659 View in Reaxys

N H

Rx-ID: 22245000 View in Reaxys 304/408 Yield

Conditions & References Reaction Steps: 2 1: Erhitzen des Reaktionsprodukts mit wss.-methanol. Salzsaeure 2: diethyl ether; sodium hydrogencarbonate; water With diethyl ether, water, sodium hydrogencarbonate Fujisawa; Deguchi; Yakugaku Zasshi; vol. 74; (1954); p. 977,979; ; (1955); p. 10959 View in Reaxys

O O

N H

Rx-ID: 22247967 View in Reaxys 305/408 Yield

Conditions & References Reaction Steps: 2 1: ethanol; sodium 2: diethyl ether; sodium hydrogencarbonate; water With diethyl ether, ethanol, water, sodium, sodium hydrogencarbonate Fujisawa; Deguchi; Yakugaku Zasshi; vol. 74; (1954); p. 977,979; ; (1955); p. 10959 View in Reaxys O O

O O

O N

Rx-ID: 22248222 View in Reaxys 306/408 Yield

Conditions & References Reaction Steps: 2 1: lithium alanate; diethyl ether 2: benzene With lithium aluminium tetrahydride, diethyl ether, benzene

99/129

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Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

O O

O N

Rx-ID: 22248224 View in Reaxys 307/408 Yield

O O

N H

Rx-ID: 22248226 View in Reaxys 308/408 Yield

Conditions & References Reaction Steps: 2 1: lithium alanate; diethyl ether 2: benzene With lithium aluminium tetrahydride, diethyl ether, benzene Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

O O

NH O

O N

Rx-ID: 22248227 View in Reaxys 309/408 Yield

100/129

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NH 2

Rx-ID: 22276393 View in Reaxys 310/408 Yield

Conditions & References Reaction Steps: 2 1: acetone; aqueous hydrogen peroxide; formic acid / Erwaermen des Reaktionsgemisches mit wss.-methanol. Schwefelsaeure 2: Erhitzen des Reaktionsprodukts mit wss.-methanol. Salzsaeure With formic acid, dihydrogen peroxide, acetone Fujisawa; Deguchi; Yakugaku Zasshi; vol. 74; (1954); p. 977,979; ; (1955); p. 10959 View in Reaxys

O O

N H

Rx-ID: 22276395 View in Reaxys 311/408 Yield

Conditions & References Reaction Steps: 3 1: acetone; aqueous hydrogen peroxide; formic acid / Erwaermen des Reaktionsgemisches mit wss.-methanol. Schwefelsaeure 2: Erhitzen des Reaktionsprodukts mit wss.-methanol. Salzsaeure 3: diethyl ether; sodium hydrogencarbonate; water With formic acid, diethyl ether, water, dihydrogen peroxide, sodium hydrogencarbonate, acetone Fujisawa; Deguchi; Yakugaku Zasshi; vol. 74; (1954); p. 977,979; ; (1955); p. 10959 View in Reaxys

O O

O O O

NH 2

Rx-ID: 22395928 View in Reaxys 312/408 Yield

Conditions & References Reaction Steps: 2 1: aq.-ethanolic KOH-solution / Ansaeuern des Reaktionsgemisches 2: ethanol; acetic acid; aqueous hydrochloric acid / Electrolysis With hydrogenchloride, potassium hydroxide, ethanol, acetic acid Bruckner; Justus Liebigs Annalen der Chemie; vol. 518; (1935); p. 226,241 View in Reaxys

O N H

Rx-ID: 29474959 View in Reaxys 313/408 Yield

Conditions & References With diphenyl phosphoryl azide, triethylamine, Reflux Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476 View in Reaxys

101/129

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O O

O S

O O

H 2N

N O

O O

Rx-ID: 29816248 View in Reaxys 314/408 Yield

Conditions & References Time= 1h, T= 55 °C Guillarme, Davy; Bonvin, Gregoire; Badoud, Flavia; Schappler, Julie; Rudaz, Serge; Veuthey, Jean-Luc; Chirality; vol. 22; nb. 3; (2010); p. 320 - 330 View in Reaxys N

O O H N

H N

H 2N

NH 2 O

O H N

H N O

NH NH

Rx-ID: 32780623 View in Reaxys 315/408 Yield

Conditions & References in water, dimethyl sulfoxide, T= 25 °C , Kinetics Moreno, Daniel; Grenu, Borja Diaz De; Garcia, Begona; Ibeas, Saturnino; Torroba, Tomas; Chemical Communications; vol. 48; nb. 24; (2012); p. 2994 - 2996

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View in Reaxys N

H N O H N

H N

HN O

O H N

H N

NH NH

Rx-ID: 32780624 View in Reaxys 316/408 Yield

O O

H 2N

N H

OH O

Rx-ID: 46678 View in Reaxys 317/408 Yield

Conditions & References With benzene Sugasawa; Sakurai; Sugimoto; Yakugaku Zasshi; vol. 59; (1939); p. 247,250; Proceedings of the Imperial Academy (Tokyo); vol. 15; (1939); p. 82,84; Chem. Zentralbl.; vol. 110; nb. II; (1939); p. 3574 View in Reaxys

103/129

2017-11-11 02:48:52

O O H 2N

N H

Rx-ID: 66983 View in Reaxys 318/408 Yield

S Cl

H 2N

N H

Rx-ID: 67949 View in Reaxys 319/408 Yield

Conditions & References With sodium hydroxide, diethyl ether Kametani; Inagaki; Yakugaku Zasshi; vol. 74; (1954); p. 417; ; (1955); p. 5495 View in Reaxys

S Cl O

H 2N

O N H

Rx-ID: 78991 View in Reaxys 320/408 Yield

Conditions & References With sodium hydroxide, diethyl ether Kametani; Inagaki; Yakugaku Zasshi; vol. 74; (1954); p. 1040; ; (1955); p. 11 659 View in Reaxys O O

N O

H 2N

Rx-ID: 147819 View in Reaxys 321/408 Yield

Conditions & References T= 140 °C Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

104/129

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O O

O N

H 2N

O N

Rx-ID: 148509 View in Reaxys 322/408 Yield

Conditions & References T= 220 °C Sugasawa et al.; Yakugaku Zasshi; vol. 60; (1940); p. 140,142; engl. Ref. S. 39, 40; ; (1940); p. 5087 View in Reaxys

O O

O H 2N

HN O

Rx-ID: 150239 View in Reaxys 323/408 Yield

Conditions & References With chloroform Govindan; Current Science; vol. 25; (1956); p. 262 View in Reaxys

O O

O O H 2N

O O

N H

O HN

O O

Rx-ID: 150240 View in Reaxys 324/408 Yield

Conditions & References T= 185 °C Kametani et al.; Yakugaku Zasshi; vol. 71; (1951); p. 325,328; ; (1952); p. 4546 View in Reaxys

105/129

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O O

O H 2N

H 2N

H N O

N H

O HN

O O

Rx-ID: 150241 View in Reaxys 325/408 Yield

Conditions & References With hydrogenchloride, diethyl ether, sodium nitrite, Reaktion ueber zwei Stufen Kametani et al.; Yakugaku Zasshi; vol. 71; (1951); p. 325,328; ; (1952); p. 4546 View in Reaxys

O H 2N

H 2N

H N

N H

O O

N H

N H N

Rx-ID: 150245 View in Reaxys 326/408 Yield

O H 2N

N H

Rx-ID: 150246 View in Reaxys 327/408 Yield

Conditions & References With ethanol, copper Ohki; Yakugaku Zasshi; vol. 70; (1950); p. 92,98; ; (1950); p. 5867 View in Reaxys

O O

H 2N

N H

Rx-ID: 150248 View in Reaxys 328/408 Yield

Conditions & References With chloroform Hey; Williams; Journal of the Chemical Society; (1951); p. 1527,1529 View in Reaxys

O O

O H 2N

N H O

Rx-ID: 150252 View in Reaxys 329/408

106/129

2017-11-11 02:48:52

Yield

Conditions & References With sodium hydroxide Morimoto; Yakugaku Zasshi; vol. 72; (1952); p. 1952> 99; ; (1952); p. 11207 View in Reaxys

H 2N

N H

Rx-ID: 150253 View in Reaxys 330/408 Yield

Conditions & References With potassium carbonate, acetone Morimoto; Yakugaku Zasshi; vol. 72; (1952); p. 1952> 95, 96; ; (1952); p. 582 View in Reaxys

O O

NH Cl

H 2N

Cl –

Rx-ID: 150258 View in Reaxys 331/408 Yield

Conditions & References With diethyl ether, sodium hydrogencarbonate, Erwaermen des Reaktionsprodukts mit Isochinolin in Benzol Fujisawa; Yakugaku Zasshi; vol. 65; (1945); p. Ausg. B, S. 555, 563; ; (1952); p. 116 View in Reaxys

H 2N

O O

N H

Rx-ID: 150260 View in Reaxys 332/408 Yield

Conditions & References With sodium hydroxide, diethyl ether Rosenmund; Chem. Zentralbl.; vol. 90; nb. I; (1919); p. 953 View in Reaxys

O O

H 2N

N H

Rx-ID: 165322 View in Reaxys 333/408 Yield

Conditions & References With methanol, Pd-BaSO4, Hydrogenation Buth; Kuelz; Rosenmund; Chemische Berichte; vol. 72; (1939); p. 19,28 View in Reaxys

107/129

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NH 2

H 2N

N H

F O

Rx-ID: 1802475 View in Reaxys 334/408 Yield

Conditions & References in isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys Br

NH 2

H 2N

N H

F O

Rx-ID: 1802476 View in Reaxys 335/408 Yield

Conditions & References in isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys N

O H 2N

NH 2

N H

Cl O

Rx-ID: 1802477 View in Reaxys 336/408 Yield

Conditions & References in isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

O O

N O

NH 2

H 2N

N N

O NH 2

Rx-ID: 1802478 View in Reaxys 337/408 Yield

Conditions & References in isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

108/129

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O O

H 2N F

H 2N

F F

F O

F NH 2 Cl

Rx-ID: 1802479 View in Reaxys 338/408 Yield

Conditions & References in isopropyl alcohol Kruger; Keck; Noll; Pieper; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 11 A; (1984); p. 1612 - 1624 View in Reaxys

H 2N

N H

Rx-ID: 9942450 View in Reaxys 339/408 Yield

Conditions & References Heating Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354 View in Reaxys

H 2N

O O

NH 2

Rx-ID: 165321 View in Reaxys 340/408 Yield

Conditions & References Erhitzen des Reaktionsprodukts mit wss. Salzsaeure Elks; Hey; Journal of the Chemical Society; (1943); p. 15 View in Reaxys Erhitzen des Reaktionsprodukts mit wss.-methanol. Salzsaeure Fujisawa; Deguchi; Yakugaku Zasshi; vol. 74; (1954); p. 977,979; ; (1955); p. 10959 View in Reaxys

quinoline-2-carbonyl chloride-hydrochloride

(+-)-2-benzo<1,3>dioxol-5-yl-methyl-ethylamine

109/129

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O O NH O N

Rx-ID: 5548870 View in Reaxys 341/408 Yield

Conditions & References Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

O OH

H 2N

O N H

Rx-ID: 150228 View in Reaxys 342/408 Yield

Conditions & References Dobrowsky; Monatshefte fuer Chemie; vol. 82; (1951); p. 122,134 View in Reaxys O O

O H 2N

Rx-ID: 150236 View in Reaxys 343/408 Yield

Conditions & References Dobrowsky; Monatshefte fuer Chemie; vol. 82; (1951); p. 122,134 View in Reaxys

NH H 2N

Rx-ID: 150237 View in Reaxys 344/408 Yield

Conditions & References Dobrowsky; Monatshefte fuer Chemie; vol. 82; (1951); p. 122,134 View in Reaxys

O H 2N

N H

Rx-ID: 150242 View in Reaxys 345/408

110/129

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Yield

Conditions & References Patent; Merck,E.; DE550122; (1929); View in Reaxys Patent; Wolfes; US1941647; (1930) View in Reaxys

O O

H 2N

N H

Rx-ID: 150243 View in Reaxys 346/408 Yield

Conditions & References Dobrowsky; Monatshefte fuer Chemie; vol. 82; (1951); p. 122,134 View in Reaxys

H 2N

N H

Rx-ID: 150244 View in Reaxys 347/408 Yield

Conditions & References Dobrowsky; Monatshefte fuer Chemie; vol. 82; (1951); p. 122,134 View in Reaxys

O O

quinoline-5-carbonyl chloride-hydrochloride O

H 2N

Rx-ID: 5548823 View in Reaxys 348/408 Yield

Conditions & References Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

quinoline-7-carbonyl chloride O

H 2N

O O

O N H

Rx-ID: 5548899 View in Reaxys 349/408 Yield

Conditions & References Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

111/129

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H N

O HO

H N

O O

NH 2

Rx-ID: 10028249 View in Reaxys 350/408 Yield

Conditions & References With cytochrome P450 2D6 wild-type, Enzyme kinetics Keizers, Peter H. J.; De Graaf, Chris; De Kanter, Frans J. J.; Oostenbrink, Chris; Feenstra, K. Anton; Commandeur, Jan N. M.; Vermeulen, Nico P. E.; Journal of Medicinal Chemistry; vol. 48; nb. 19; (2005); p. 6117 - 6127 View in Reaxys With cytochrome P450 2D6 Phe120Ala mutant, Enzyme kinetics Keizers, Peter H. J.; De Graaf, Chris; De Kanter, Frans J. J.; Oostenbrink, Chris; Feenstra, K. Anton; Commandeur, Jan N. M.; Vermeulen, Nico P. E.; Journal of Medicinal Chemistry; vol. 48; nb. 19; (2005); p. 6117 - 6127 View in Reaxys OH

H N

NH 2

Rx-ID: 10047698 View in Reaxys 351/408 Yield

H N

O O

H N

NH 2

Rx-ID: 10055435 View in Reaxys 352/408 Yield

H N

O O

H N

O HO

O O

NH 2

Rx-ID: 10055436 View in Reaxys 353/408

112/129

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Yield

H N

NH 2

Rx-ID: 10061848 View in Reaxys 354/408 Yield

N H

H 2N

Rx-ID: 149186 View in Reaxys 355/408 Yield

Conditions & References Govindan; Proceedings - Indian Academy of Sciences, Section A; nb. 44; (1956); p. 126,127 View in Reaxys

O H 2N

O O

N H

Rx-ID: 150234 View in Reaxys 356/408 Yield

Conditions & References Patent; Rosenmund; DE336153; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 13; p. 884 View in Reaxys

113/129

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O O NH

H 2N

Rx-ID: 150257 View in Reaxys 357/408 Yield

Conditions & References Reaktion ueber mehrere Stufen Fujisawa; Yakugaku Zasshi; vol. 65; (1945); p. Ausg. B, S. 555, 563; ; (1952); p. 116 View in Reaxys

NH 2

Rx-ID: 5446367 View in Reaxys 358/408 Yield

Conditions & References T= 0 °C , Erhitzen des Reaktionsprodukts mit waessr. Ammoniak auf 120 Patent; Merck; DE274350; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 12; p. 768 View in Reaxys H N

O S

cadmium cathode O

NH 2

Rx-ID: 5446368 View in Reaxys 359/408 Yield

Conditions & References bei der elektrolytischen Reduktion Kindler; Justus Liebigs Annalen der Chemie; vol. 431; (1923); p. 213; Chem. Zentralbl.; vol. 94; nb. II; (1923); p. 403 View in Reaxys H N

O S

lead cathode O

NH 2

Rx-ID: 5446369 View in Reaxys 360/408 Yield

Conditions & References bei der elektrolytischen Reduktion Kindler; Justus Liebigs Annalen der Chemie; vol. 431; (1923); p. 213; Chem. Zentralbl.; vol. 94; nb. II; (1923); p. 403 View in Reaxys

sodium amalgam O

NH 2

Rx-ID: 5446371 View in Reaxys 361/408 Yield

Conditions & References Mannich; Jacobsohn; Chemische Berichte; vol. 43; (1910); p. 193

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View in Reaxys

O 13 C O

13C

H C

C H

NH 2

13C

HCl

Rx-ID: 38217568 View in Reaxys 362/408 Yield

Conditions & References

75 %

3.5 : 3.5 The hydrochloride salt was formed by slow addition of a HCl saturated solution in diethyl ether until pH 5. The salt was filtered from the solvent with a dry Buchner funnel and the product was washed by adding chilled diethyl ether (2*10 mL). The product was dried under reduced pressure to yield the product (800 mg, 75percent) with a purity greater than 99percent by TFAA derivatization on GC/MS. With hydrogenchloride in diethyl ether Patent; CHIRON A/S; Johansen, Jon Eigill; Liu, Huiling; Karlsen, Morten; US2014/227792; (2014); (A1) English View in Reaxys

O O

N H

Rx-ID: 5452498 View in Reaxys 363/408 Yield

Conditions & References α-(3,4-Methylendioxyphenyl)-β-brompropan, ethanol. MeNH2-Loesg., Erhitzen im zugeschmolzenen Rohr Biniecki; Krajewski; Acta Poloniae Pharmaceutica; vol. 17; (1960); p. 421,422, 423; ; vol. 55; nb. 14350; (1961) View in Reaxys α-(3,4-Methylendioxyphenyl)-β-brompropan, Methylamin/A. (Erhitzen im zugeschmolzenen Rohr) Biniecki; Krajewski; Acta Poloniae Pharmaceutica; vol. 17; (1960); p. 421,422, 423; ; vol. 55; nb. 14350; (1961) View in Reaxys 2 : Preparation of 3,4-methylenedioxymethamphetamine (MDMA) 1 Example-2 Preparation of 3,4-methylenedioxymethamphetamine (MDMA) 1 Compound 5 (4 g, 0.022 mol) was dissolved in methanol (100 ml) and to this stirred solution was added, methylamine hydrochloride (15.16 g, 0.22 mol) and triethylamine (6.76 ml, 0.049 mol). Sodium cyanoborohydride (1.41 g, 0.022 mol) in methanol (10 ml) was added in one portion and the reaction mixture stirred at room temperature overnight. The solvents were removed in vacuo, water (50 ml) followed by 1N HCl (50 ml) was added and the mixture washed with diethyl ether (100 ml). The aqueous phase was basified to pH 12-13 with 2N NaOH and extracted with ethyl acetate (3*100 ml). The combined organic extracts were dried over sodium sulphate, filtered and the solvent was removed to give crude MDMA (compound 1) free base as brown oil in good yield. The crude product obtained was used without further purification. FT-IR (film, neat): 3172, 2779.3, 2715.4, 1246.7 and 1037.9 cm-1 () Patent; McConnell, Robert Ivan; Benchikh, Elouard; Fitzgerald, Stephen Peter; Lamont, John Victor; US2004/121400; (2004); (A1) English View in Reaxys

O O

N H

Rx-ID: 6580953 View in Reaxys 364/408

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Yield

Conditions & References Keton 15b, H2/Pd/C Sohda et al.; Journal of Medicinal Chemistry; vol. 22; (1979); p. 279,285 View in Reaxys Keton 15b, H2, Pd/C Sohda et al.; Journal of Medicinal Chemistry; vol. 22; (1979); p. 279,285 View in Reaxys Step G2: Synthesis of 1-(4-hydroxy-3-methoxymethylphenyl)-2-(α-methyl-3,4-methylenedioxyphenethylamino)ethanol An amount of 7.7 g of the hydrochloride obtained in the step F2 is dissolved in 80 ml of methanol, and the solution is subjected to the hydrogenolysis in the presence of palladium-carbon in accordance with the Example 1 (Step E 1, b). The reactants are then alkalified with aqueous ammonia. The object compound is extracted with ether. The object compound is crystallized as the oxalate, which is purified by recrystallizing from aqueous methanol. Yield: 4.5 g. Melting point: 202.5° C. (with decomposition). Elementary analysis of the product for C20 H25 NO5.1/2C 2 H2 O4 gives: NMR(DMSO-d6, TMS): δ: 4.41 ppm (2H, s, CH2 OCH3); 3.35 (3H, s, CH2 OCH3). Patent; Eisai Co., Ltd.; US4317930; (1982); (A1) English View in Reaxys

O O

NH 2

N H

Rx-ID: 23972067 View in Reaxys 365/408 Yield

Conditions & References 4 : Preparation of N-(4'-aminobutyl)-3,4-methylenedioxyamphetamine (AB-MDA) Example 4 Preparation of N-(4'-aminobutyl)-3,4-methylenedioxyamphetamine (AB-MDA) N-boc-AB-MDA (300 mg) was dissolved in trifluoroacetic acid (2 ml) in an amber glass vial. A magnetic stirrer was added to the reaction mixture. The reaction mixture was stirred for one hour. TFA was removed under reduced pressure. The off-white solid product was stored at -80° C. until further use. Patent; Microgenics Corporation; US2003/207469; (2003); (A1) English View in Reaxys

O O

N H

Rx-ID: 25151985 View in Reaxys 366/408 Yield

Conditions & References 11.3 : EXAMPLE 11 (3) A mixture of the α-(α-methyl-3,4-methylenedioxyphenethylimino)-B 2-chloroacetophenone solution obtained in paragraph (2), 1.73 g of sodium borohydride and 30 ml of ethanol is treated in the same manner as described in Example 1-(3), whereby α-[(α-methyl-3,4-methylenedioxyphenethylamino)methyl]-2-chlorobenzylalcohol [the mixture of two diastereoisomers] is obtained as a crude oil. Patent; Tanabe Seiyaku Co., Ltd.; US4490392; (1984); (A1) English View in Reaxys

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O O NH H

O O

Rx-ID: 25153502 View in Reaxys 367/408 Yield

Conditions & References 33 : 1-[1-(3,4-methylenedioxy-phenyl)-2-propyl]-aminomethyl-4,5-methylenedioxy-phthalan HCl EXAMPLE 33 1-[1-(3,4-methylenedioxy-phenyl)-2-propyl]-aminomethyl-4,5-methylenedioxy-phthalan HCl The procedure of Example 5 is repeated using 1-[1-(3,4-methylenedioxy-phenyl)-2-propyl]-aminomethyl-4,5-methylenedioxy-phthalide HCl as the starting material to obtain 1-[1-(3,4-methylenedioxy-phenyl)-2-propyl]-aminomethyl-4,5methylenedioxy-phthalan HCl. Patent; Abbott Laboratories; US4500543; (1985); (A1) English View in Reaxys

O O NH OH

NH 2 OH

Rx-ID: 25436818 View in Reaxys 368/408 Yield

Conditions & References 1 : (R)-1-(3-amino-4-hydroxyphenyl)-2-[(S)-1-methyl-2-(3,4-methylenedioxyphenyl)ethylamino]ethanol (IX) (R)-1-(3-amino-4-hydroxyphenyl)-2-[(S)-1-methyl-2-(3,4-methylenedioxyphenyl)ethylamino]ethanol (IX) 4.3 g (8 mmol) of the previous compound (R,S,S,-isomer) - as hydrochloride -was dissolved in 75 ml of methanol. 0.3 g of 10percent Pd/C was added and the mixture hydrogenated at 40 psi for 5 h. The methanol solution was filtered and this solution was used in the next step. The S,S,S,- R,R,R and S,R,R-isomers of (IX) were prepared in a similar way. Patent; Aktiebolaget Draco; EP390762; (1990); (A1) English View in Reaxys

O O

NH 2

Rx-ID: 5446365 View in Reaxys 369/408 Yield

Conditions & References Ho,B.T. et al.; Journal of Medicinal Chemistry; vol. 13; (1970); p. 26 - 30 View in Reaxys Bernhard,H.O.; Snieckus,V.; Tetrahedron; vol. 27; (1971); p. 2091 - 2100 View in Reaxys Bernhard; Snieckus; Tetrahedron; vol. 27; (1971); p. 2091,2097

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View in Reaxys Butterick; Unrau; Journal of the Chemical Society, Chemical Communications; (1974); p. 307 View in Reaxys Ibanez Paniello; Anales de Quimica (1968-1979); vol. 72; (1976); p. 814,815,817 View in Reaxys BINIECKI; MUSZYNSKI; JAGIELLOWICZ; CHOJNACKA; Acta poloniae pharmaceutica; vol. 19; (1962); p. 31 - 35 View in Reaxys Biniecki et al.; Acta Poloniae Pharmaceutica; vol. 19; (1962); p. 257,260; ; vol. 60; nb. 4147; (1964) View in Reaxys HO

O OH

O O

N H

Rx-ID: 6554126 View in Reaxys 370/408 Yield

Conditions & References Base 73, frakt. Krist. (Trennung d. Stereoisomerengemischs 73) de Antoni; Eche; Guillemot; et al.; European Journal of Medicinal Chemistry; vol. 13; nb. 6; (1978); p. 545 - 552 View in Reaxys Benzylamin-Der. 49, 1.) H2-Pd/C, 2.) frakt. Kristallis. de Antoni; Eche; Guillemot; et al.; European Journal of Medicinal Chemistry; vol. 13; nb. 6; (1978); p. 545 - 552 View in Reaxys aus Base 73 de Antoni; Eche; Guillemot; et al.; European Journal of Medicinal Chemistry; vol. 13; nb. 6; (1978); p. 545 - 552 View in Reaxys Benzylamin..??.. 49, H2, Pd/C de Antoni; Eche; Guillemot; et al.; European Journal of Medicinal Chemistry; vol. 13; nb. 6; (1978); p. 545 - 552 View in Reaxys

O O

HO OH O S

Rx-ID: 6557381 View in Reaxys 371/408 Yield

Conditions & References Sulfonanilid 19, H2/Pd Banitt; Coyne; McGurran; Robertson; Journal of Medicinal Chemistry; vol. 17; nb. 1; (1974); p. 116 - 120 View in Reaxys Sulfonanilid 19, H2, Pd Banitt; Coyne; McGurran; Robertson; Journal of Medicinal Chemistry; vol. 17; nb. 1; (1974); p. 116 - 120 View in Reaxys

118/129

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O O

N H

Rx-ID: 6581980 View in Reaxys 372/408 Yield

Conditions & References 4-Benzyloxy-3-methylsulfonylmethyl-ω-<1-(3.4-methylendioxy-benzyl)-ethylimino>-acetophenon, 1) Ethanol, NaBH4, 2) wss. Ethanol, H2 (Pd-Kohle) Kaiser; Schwartz; Colella; Wardell Jr.; Journal of Medicinal Chemistry; vol. 18; nb. 7; (1975); p. 674 - 683 View in Reaxys 4-Benzyloxy-3-methylsulfonylmethyl-ω-<1-(3,4-methylendioxy-benzyl)-aethylimino>-acetophenon in A., 1) NaBH4, 2) in wss. A., H2 <Pd-Kohle> Kaiser; Schwartz; Colella; Wardell Jr.; Journal of Medicinal Chemistry; vol. 18; nb. 7; (1975); p. 674 - 683 View in Reaxys

N H

NH 2

Rx-ID: 6548958 View in Reaxys 373/408 Yield

Conditions & References geschuetztes Amid 13, H2 Mazur,R.H. et al.; Journal of Medicinal Chemistry; vol. 13; (1970); p. 1217 - 1221 View in Reaxys

O O

NH O O

Rx-ID: 6560576 View in Reaxys 374/408 Yield

Conditions & References entspr. Amin, entspr. p-Nitrophenylester Mazur,R.H. et al.; Journal of Medicinal Chemistry; vol. 13; (1970); p. 1217 - 1221 View in Reaxys O O

O O

S N

Rx-ID: 6562197 View in Reaxys 375/408

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Yield

Conditions & References Phenacylbromid Vb, 1-(2-Amino-n-propyl)-3,4-dioxomethylenbenzol Banitt; Coyne; McGurran; Robertson; Journal of Medicinal Chemistry; vol. 17; nb. 1; (1974); p. 116 - 120 View in Reaxys

O O

N H

Rx-ID: 6546811 View in Reaxys 376/408 Yield

Conditions & References Phthalid 1c, Hydrierung Walker,G.N.; Kempton,R.J.; Journal of Organic Chemistry; vol. 36; (1971); p. 1413 - 1416 View in Reaxys

O O

O Cl

N H

Rx-ID: 6575567 View in Reaxys 377/408 Yield

Conditions & References β-(3,4-Methylendioxyphenyl)-isopropylamin, Chloracetylchlorid, Pyridin Bernhard,H.O.; Snieckus,V.; Tetrahedron; vol. 27; (1971); p. 2091 - 2100 View in Reaxys β-(3,4-Methylendioxy-phenyl)-isopropylamin, ClCH2-CO-Cl/Py. Bernhard,H.O.; Snieckus,V.; Tetrahedron; vol. 27; (1971); p. 2091 - 2100 View in Reaxys

O O

N H

NH 2

Rx-ID: 5459073 View in Reaxys 378/408 Yield

Conditions & References aus <3,4-Methylendioxy-phenyl>-aceton, 1) Hydrazinhydrat in Me., 2) H2 <Pt> in A.+Eg. Patent; Lakeside Labor.; US3000903; (1959); ; vol. 56; nb. 1393; (1962) View in Reaxys aus 2-Hydrazono-1-<3,4-methylendioxy-phenyl>-propan, H2 <Pt> in A.+Eg. Patent; Lakeside Labor.; US2978461; (1958); ; nb. 25861; (1961) View in Reaxys

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O O

Rx-ID: 5952557 View in Reaxys 379/408 Yield

Conditions & References 2-p-Tolyl-4-methyl-5-pyrimidincarbonsaeureazid (IIc), α-Methyl-3,4-methylendioxy-phenethylamin (V), Ethylacetat Morimoto; Yakugaku Zasshi; vol. 82; (1962); p. 386,388; ; vol. 58; nb. 3421; (1963) View in Reaxys 2-p-Tolyl-4-methyl-5-pyrimidin-carbonsaeurechlorid*HCl (Ic), α-Methyl-3,4-methylendioxy-phenethylamin (V), K2CO3, CHCl3 Morimoto; Yakugaku Zasshi; vol. 82; (1962); p. 386,388; ; vol. 58; nb. 3421; (1963) View in Reaxys Ethyl-2-p-tolyl-4-methyl-5-pyrimidincarboxylat, α-Methyl-3,4-methylendioxy-phenethylamin (V), 230 grad Morimoto; Yakugaku Zasshi; vol. 82; (1962); p. 386,388; ; vol. 58; nb. 3421; (1963) View in Reaxys

O O

N H

Rx-ID: 5488642 View in Reaxys 380/408 Yield

Conditions & References aus α-Methylhomopiperonylamin, Acetanhydrid Pecherer,B. et al.; Journal of Heterocyclic Chemistry; vol. 9; (1972); p. 609 - 616 View in Reaxys α-Methylhomopiperonylamin, Acetanhydrid Pecherer,B. et al.; Journal of Heterocyclic Chemistry; vol. 9; (1972); p. 609 - 616 View in Reaxys

O O

O N H

Rx-ID: 5526630 View in Reaxys 381/408 Yield

Conditions & References DL-β-(3',4'-Methylendioxy-phenyl)-isopropylamin, Benzoylchlorid BINIECKI; MUSZYNSKI; JAGIELLOWICZ; CHOJNACKA; Acta poloniae pharmaceutica; vol. 19; (1962); p. 31 - 35 View in Reaxys D,L-β-(3',4'-Methylendioxyphenyl)-isopropyl-amin, C6H5COCl BINIECKI; MUSZYNSKI; JAGIELLOWICZ; CHOJNACKA; Acta poloniae pharmaceutica; vol. 19; (1962); p. 31 - 35 View in Reaxys

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O O

O N

N H

Rx-ID: 6511610 View in Reaxys 382/408 Yield

Conditions & References N-Chloracetyl-α-methyl-3,4-methylendioxyphenethylamin, Piperidin, Benzol (Rohr; Dampfbad) Takagi et al.; Chemical and Pharmaceutical Bulletin; vol. 11; (1963); p. 654,655 View in Reaxys

O O

O N

N H

Rx-ID: 6512172 View in Reaxys 383/408 Yield

Conditions & References N-(2-Halogen-propionyl)-α-methyl-3,4-methylendioxy-phenethylamin, Piperidin, Benzol (Rohr, Dampfbad) Takagi et al.; Chemical and Pharmaceutical Bulletin; vol. 11; (1963); p. 654,655 View in Reaxys

O O

O N H

Rx-ID: 6536772 View in Reaxys 384/408 Yield

Conditions & References α-Methyl-3,4-methylendioxy-phenaethylamin in Ae., Propionylchlorid, wss. K2CO3 Takagi et al.; Chemical and Pharmaceutical Bulletin; vol. 11; (1963); p. 654,655 View in Reaxys

O O

O N H

Rx-ID: 6537963 View in Reaxys 385/408 Yield

Conditions & References α-Methyl-3,4-methylendioxy-phenaethylamin, Butyrylchlorid, wss. K2CO3, Ae. Takagi et al.; Chemical and Pharmaceutical Bulletin; vol. 11; (1963); p. 654,655 View in Reaxys

O O

O N H

Rx-ID: 6540178 View in Reaxys 386/408 Yield

Conditions & References α-Methyl-3,4-methylendioxy-phenaethylamin in Ae., 2-Brom-propionylchlorid, wss. K2CO3 Takagi et al.; Chemical and Pharmaceutical Bulletin; vol. 11; (1963); p. 654,655 View in Reaxys

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O O

NH 2 Br

Rx-ID: 6550697 View in Reaxys 387/408 Yield

Conditions & References 2-Amino-α,3,5-tribromacetophenon, 1.) /BRN= 150196/, 2.) NaBH4 Keck; Krueger; Noll; Machleidt; Arzneimittel-Forschung; vol. 22; nb. 5; (1972); p. 861 - 869 View in Reaxys 2-Amino-α,3,5-tribromacetophenon, 1) /BRN= 150196/ 2) NaBH4 Keck; Krueger; Noll; Machleidt; Arzneimittel-Forschung; vol. 22; nb. 5; (1972); p. 861 - 869 View in Reaxys Br NH 2

O O

N H

Cl OH

Rx-ID: 6552975 View in Reaxys 388/408 Yield

Conditions & References /BRN= 786667/, 1.) /BRN= 150196/, 2.) NaBH4 Keck; Krueger; Noll; Machleidt; Arzneimittel-Forschung; vol. 22; nb. 5; (1972); p. 861 - 869 View in Reaxys /BRN= 786667/, 1) /BRN= 150196/ 2) NaBH4 Keck; Krueger; Noll; Machleidt; Arzneimittel-Forschung; vol. 22; nb. 5; (1972); p. 861 - 869 View in Reaxys Cl NH 2

O O

N H

Cl OH

Rx-ID: 6552976 View in Reaxys 389/408 Yield

Conditions & References 4-Amino-3,5-dichlorphenacylbromid, 1.) /BRN= 150196/, 2.) NaBH4 Keck; Krueger; Noll; Machleidt; Arzneimittel-Forschung; vol. 22; nb. 5; (1972); p. 861 - 869 View in Reaxys 4-Amino-3,5-dichlor-phenacylbromid, 1) /BRN= 150196/ 2) NaBH4 Keck; Krueger; Noll; Machleidt; Arzneimittel-Forschung; vol. 22; nb. 5; (1972); p. 861 - 869 View in Reaxys Br NH 2

O O

N H

Br OH

Rx-ID: 6552978 View in Reaxys 390/408

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Yield

Conditions & References 4-Amino-α,3,5-tribromacetophenon, 1.) /BRN= 150196/, 2.) NaBH4 Keck; Krueger; Noll; Machleidt; Arzneimittel-Forschung; vol. 22; nb. 5; (1972); p. 861 - 869 View in Reaxys 4-Amino-α,3,5-tribromacetophenon, 1) /BRN= 150196/ 2) NaBH4 Keck; Krueger; Noll; Machleidt; Arzneimittel-Forschung; vol. 22; nb. 5; (1972); p. 861 - 869 View in Reaxys H N

O O

N H

O OH

Rx-ID: 6554580 View in Reaxys 391/408 Yield

Conditions & References 1-(p-Acetamidophenoxy)-2,3-epoxypropan (IX), 1-Methyl-2-(3,4-methylendioxyphenyl)-ethylamin, Δ in wssfr.A. Ibanez Paniello; Anales de Quimica (1968-1979); vol. 72; (1976); p. 814,815,817 View in Reaxys 1-(p-Acetamidophenoxy)-2.3-epoxypropan (IX), 1-Methyl-2-(3,4-methylendioxyphenyl)ethylamin, wfr. A., Erh. Ibanez Paniello; Anales de Quimica (1968-1979); vol. 72; (1976); p. 814,815,817 View in Reaxys

O O

O N

N H

Rx-ID: 6577161 View in Reaxys 392/408 Yield

Conditions & References N-<2-Halogen-propionyl>-α-methyl-3,4-methylendioxy-phenaethylamin, Dimethylamin in Bzl. i. Rohr (Dampfbad) Takagi et al.; Chemical and Pharmaceutical Bulletin; vol. 11; (1963); p. 654,655 View in Reaxys

O O

O N H

Rx-ID: 6578115 View in Reaxys 393/408 Yield

Conditions & References N-<2-Halogen-propionyl>-α-methyl-3,4-methylendioxy-phenaethylamin, Diaethylamin in Bzl. i. Rohr (Dampfbad) Takagi et al.; Chemical and Pharmaceutical Bulletin; vol. 11; (1963); p. 654,655 View in Reaxys

O O

N H

Rx-ID: 6578926 View in Reaxys 394/408 Yield

Conditions & References D,L-<β-(3,4-Methylendioxy-phenyl)>-α-methyl-α-(3',4'-dimethoxy-phenyl-azametheno)-ethan, Hydrier. an PtO2/ wfr.Ethanol/erhoehter Druck Biniecki et al.; Acta Poloniae Pharmaceutica; vol. 19; (1962); p. 257,260; ; vol. 60; nb. 4147; (1964)

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View in Reaxys DL-<β-(3,4-Methylendioxy-phenyl)>-α-methyl-α-(3',4'-dimethoxy-phenyl-azametheno)-ethan, wfr. A., Hydrierung an PtO2 unter erhoehtem Druck Biniecki et al.; Acta Poloniae Pharmaceutica; vol. 19; (1962); p. 257,260; ; vol. 60; nb. 4147; (1964) View in Reaxys

O O

N H O O

Rx-ID: 6579190 View in Reaxys 395/408 Yield

Conditions & References D,L-<β-(3,4-Methylendioxyphenyl)>-α-methyl-α-(3',4'-methylendioxyphenyl-azamethin)-ethan, Hydrier. an PtO2/ wfr.Ethanol/erhoehter Druck BINIECKI; MUSZYNSKI; JAGIELLOWICZ; CHOJNACKA; Acta poloniae pharmaceutica; vol. 19; (1962); p. 31 - 35 View in Reaxys DL-<β-(3,4-Methylendioxyphenyl)>-α-methyl-α-(3',4'-methylendioxyphenyl-azamethin)-ethan, wfr. A., Hydrierung an PtO2 unter erhoehtem Druck BINIECKI; MUSZYNSKI; JAGIELLOWICZ; CHOJNACKA; Acta poloniae pharmaceutica; vol. 19; (1962); p. 31 - 35 View in Reaxys

O O

HN HN O O

Rx-ID: 6581316 View in Reaxys 396/408 Yield

Conditions & References 3,4-Methylendioxyphenyl-isopropylamin, Formalin Muszynski; Acta Poloniae Pharmaceutica; vol. 22; (1965); p. 215,217 View in Reaxys 3,4-Methylendioxyphenyl-isopropyl-amin, Formalin Muszynski; Acta Poloniae Pharmaceutica; vol. 22; (1965); p. 215,217 View in Reaxys

125/129

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O O

Rx-ID: 6583367 View in Reaxys 397/408 Yield

Conditions & References 3,4-Methylendioxyphenyl-isopropylamin, Diethyloxalat Muszynski; Acta Poloniae Pharmaceutica; vol. 22; (1965); p. 215,217 View in Reaxys 3,4-Methylendioxyphenyl-isopropyl-amin, Diethyloxalat Muszynski; Acta Poloniae Pharmaceutica; vol. 22; (1965); p. 215,217 View in Reaxys

O O

N H

Rx-ID: 8398864 View in Reaxys 398/408 Yield

Conditions & References <β-(3,4-Methylendioxyphenyl)>-N-benzyliden-isopropyl-amin, H2/PtO2 Muszynski; Acta Poloniae Pharmaceutica; vol. 22; (1965); p. 109,113 View in Reaxys β-(3,4-Methylendioxyphenyl)-N-benzyliden-isopropylamin, H2/PtO2 Muszynski; Acta Poloniae Pharmaceutica; vol. 22; (1965); p. 109,113 View in Reaxys

O O

N H

Rx-ID: 8399921 View in Reaxys 399/408 Yield

Conditions & References β-(3,4-Methylendioxyphenyl)-N-furfuryliden-isopropyl-amin, H2/PtO2 Muszynski; Acta Poloniae Pharmaceutica; vol. 22; (1965); p. 109,113 View in Reaxys β-(3,4-Methylendioxyphenyl)-N-furfuryliden-isopropylamin, H2/PtO2 Muszynski; Acta Poloniae Pharmaceutica; vol. 22; (1965); p. 109,113 View in Reaxys

126/129

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N H

Rx-ID: 8400883 View in Reaxys 400/408 Yield

Conditions & References β-(3,4-Methylendioxyphenyl)-isopropyl-amin, H2/PtO2 Muszynski; Acta Poloniae Pharmaceutica; vol. 22; (1965); p. 109,113 View in Reaxys β-(3,4-Methylendioxyphenyl)-N-(o-hydroxybenzyliden)-isopropylamin, H2/PtO2 Muszynski; Acta Poloniae Pharmaceutica; vol. 22; (1965); p. 109,113 View in Reaxys O O

Rx-ID: 5908048 View in Reaxys 401/408 Yield

Conditions & References 2-Phenyl-4-methyl-5-pyrimidin-carbonsaeurechlorid*HCl (Ia), α-Methyl-3,4-methylendioxy-phenethylamin (V), K2CO3, Aceton Morimoto; Yakugaku Zasshi; vol. 82; (1962); p. 386,388; ; vol. 58; nb. 3421; (1963) View in Reaxys O O

Rx-ID: 5911614 View in Reaxys 402/408 Yield

Conditions & References α-Methyl-3,4-methylendioxy-phenethylamin (V), 2-o-Tolyl-4-methyl-5-pyrimidincarbonsaeurechlorid*HCl (2b), K2CO3, CHCl3 Morimoto; Yakugaku Zasshi; vol. 82; (1962); p. 386,388; ; vol. 58; nb. 3421; (1963) View in Reaxys

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O O

O N N O

Rx-ID: 6379011 View in Reaxys 403/408 Yield

Conditions & References entspr. Alkylaminoxanthin, entspr. Keton,Pt/H2 Patent; DEGUSSA; FR1352320; (1964); DE; ; vol. 61; nb. 3125d; (1964) View in Reaxys

N H

S N

Rx-ID: 6493835 View in Reaxys 404/408 Yield

Conditions & References 5-Nitro-thiophen-2-carbonsaeure, 1) Thionylchlorid, Δ, 2) α-Methyl-3,4-methylendioxy-phenaethylamin, Δ Kametani et al.; Yakugaku Zasshi; vol. 83; (1963); p. 174,176; ; vol. 59; nb. 6365; (1963) View in Reaxys NH 2 Cl

O O

N H

Rx-ID: 6550539 View in Reaxys 405/408 Yield

Conditions & References /BRN= 375886/, 1) /BRN= 150196/ 2) NaBH4 3) HCl Keck; Krueger; Noll; Machleidt; Arzneimittel-Forschung; vol. 22; nb. 5; (1972); p. 861 - 869 View in Reaxys

O O

Rx-ID: 6581560 View in Reaxys 406/408 Yield

Conditions & References N,N'-Bis-<β-(3,4-methylendioxyphenyl)-isopropyl>-oxamid, LiAlH4

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Muszynski; Acta Poloniae Pharmaceutica; vol. 22; (1965); p. 215,217 View in Reaxys

O O

Cl N

O N N O

Rx-ID: 8385210 View in Reaxys 407/408 Yield

Conditions & References aus entspr. Aminoalkyltheophyllin, entspr. Keton, Pt/H2 Patent; Degussa; BE630294; (1963); ; vol. 61; nb. 1878d; (1964) View in Reaxys

N H

H HCl

Rx-ID: 10841270 View in Reaxys 408/408 Yield

Conditions & References 11 Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English View in Reaxys

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