2-(2,5-dimethoxyphenyl)ethan-1-amine (2C-H) by Asch

Query Query

Results

Date

177 reactions in Reaxys

2016-04-19 04h:34m:43s (EST)

O NH 2

1. Query

Search as: As drawn

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O O

N Cl

N H

NH N

H 2N

Rx-ID: 32653868 View in Reaxys 1/177 Yield

Conditions & References

72.4 %

7.1.2. General procedure for the preparation of acylamides (compound 4a-4k) General procedure: A mixture of amines (1.1 mmol), dichloromethane (30 mL) and triethylamine (0.3 g, 3 mmol) was placed in a three-necked bottle and cooled with ice. Then 4-methyl-2-propyl-1H-benzimidazole-6-carboxylic chloride (3) (0.24 g, 1 mmol) was added slowly. After the addition, the mixture was stirred at room temperature for 6 h. The white precipitate formed in the mixture was filtered, the filtrate was evaporated and the solid obtained was washed with saturated sodium bicarbonate and brine. The obtained acylamides was recrystallized from ethanol. With triethylamine in dichloromethane, Time= 6h, T= 20 °C , Cooling with ice Wang, Jin-Liang; Zhang, Jun; Zhou, Zhi-Ming; Li, Zhi-Huai; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, XiaoFeng; Fei, Fan; Liu, Ting; Liang, Ai-Hua; European Journal of Medicinal Chemistry; vol. 49; (2012); p. 183 - 190 View in Reaxys

2.75 g

4.1.2. General synthetic procedure for 4a-4k General procedure: To a stirred suspension of the resulting acid chloride in 60 mL of chloroform at 0 °C was added dropwise to triethylamine (1.52 g, 15 mmol), followed by a solution of one of the substituted amines (10 mmol) in 10 mL of chloroform. The resulting mixture was stirred at 25 °C for 8 h. The reaction mixture was filtered, and the filtrate was washed with brine, saturated sodium bicarbonate solution, brine and water, dried over anhydrous sodium sulphate, filtered, and concentrated under a vacuum. The residue was purified by recrystallisation in ethanol to provide pure product as white solids. With triethylamine in chloroform, Time= 8h, T= 0 - 25 °C Zhang, Jun; Wang, Jin-Liang; Zhou, Zhi-Ming; Li, Zhi-Huai; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, XiaoFeng; Fei, Fan; Liu, Ting; Liang, Ai-Hua; Bioorganic and Medicinal Chemistry; vol. 20; nb. 14; (2012); p. 4208 4216 View in Reaxys

O N O

H 2N

NH 2 O

Rx-ID: 9385449 View in Reaxys 2/177 Yield

Conditions & References With nitrating agent in water Acuna-Castillo, Claudio; Villalobos, Claudio; Moya, Pablo R; Saez, Patricio; Cassels, Bruce K; HuidobroToro, J Pablo; British journal of pharmacology; vol. 136; nb. 4; (2002); p. 510 - 519 View in Reaxys

5.4 g (91%)

5.A : A. A. Synthesis of Intermediate 33-(2,5-Dimethoxy-4-nitrophenethylamine) To a 100-mL Erlenmeyer flask equipped with a magnetic stirring bar were added 4.73 g (26.1 mmol) of 2,5-dimethoxyphenethylamine (32) (Trans World Chemicals Inc., 98percent) and 4.2 mL of water. The mixture was stirred and cooled to 0° C. in an ice bath and 3.1 mL of conc. HCl was added slowly. To the resulting yellow solution 3.4 mL of conc. HNO3 was added dropwise at 0-5° C. over a period of 1 h. Then 12 mL of water was added to the solidified mixture and swirled to form a stirrable paste. Then another 3.4 mL of conc. HNO3 was added dropwise at 0-5° C. over a period of 1 h. The yellow mixture was refrigerated for 12 h., then 20 mL of water was added and ultrasonicated to brake big chunks of solid. The suspension was cooled to 0° C. in an ice bath and 10 mL of 40percent NaOH was added slowly to achieve pH 12-13.

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The mixture was extracted with CHCl3 (3*10 mL) and the combined extract was washed with 0.5 N NaOH (3*10 mL), dried over K2CO3 (3 g) and evaporated to dryness (15 mm) to give 5.4 g (91percent) of 33 as a brown oil which solidified after 0.5 h at room temperature. 1H NMR (300 MHz, CDCl3): δ7.43 (s, 1H, H3), 6.96 (s, 1H, H6), 3.95 (s, 3H, H10), 3.85 (s, 3H, H9), 3.00 (t, J=6.9 Hz, 2H, H8), 2.85 (t, J=6.9 Hz, 2H, H7), 2.06 (s, 2H, NH2); 13C NMR (75.7 MHz, CDCl3): δ150.6, 147.3, 136.8, 136.5, 116.2, 107.2, 56.9, 55.8, 41.6, 34.9. FAB-MS, m/z (rel. intensity): 227.3 (M+1, 100). For microanalysis crude 33was recrystallized from a 1:5 mixture of EtOAc/hexane and dried under vacuum (0.1 mm, RT) for 2 days; mp 64-66° C. Anal. Calcd for C10H14N2O4: C, 53.09; H, 6.23; N, 12.38percent. Found: C, 53.04; H, 6.03; N, 12.30percent. With conc. HNO3 in hydrochlorid acid, sodium hydroxide, water Patent; Roche Diagnostics Corporation; US6525200; (2003); (B1) English View in Reaxys 3 : Preparation of 2-(2,5-dimethoxy-4-nitrophenyl)ethanamine 4 Example 3 Preparation of 2-(2,5-dimethoxy-4-nitrophenyl)ethanamine 4 2-(2,5-Dimethoxyphenyl) ethanamine 3 (5.76 g, 31.78 mmol) was dissolved in a mixture of acetic acid (115 ml) and nitric acid (19 ml) with cooling at 0° C. The reaction mixture was stirred for 1 hour at 0° C. The reaction mixture was poured over a mixture of water and ice and 6M sodium hydroxide was used to bring the pH to alkaline. Then the solution was extracted with a mixture of (1/1) benzene/ether. The organic layer was dried over sodium sulfate, filtered and was evaporated to dryness to give 6.16 g of 2-(2,5dimethoxy-4-nitrophenyl) ethanamine 4 as dark brown crude oil used in the next step without any further purification. With sodium hydroxide in water, acetic acid, benzene Patent; Benchikh, Elouard; Fitzgerald, Peter; McConnell, Ivan; Lowry, Philip; US2015/38366; (2015); (A1) English View in Reaxys 3 : Example 3 Example 3 Preparation of 2-(2,5-dimethoxy-4-nitrophenyl)ethanamine 4 2-(2,5-Dimethoxyphenyl) ethanamine 3 (5.76g, 31.78mmol) was dissolved in a mixture of acetic acid (115ml) and nitric acid (19ml) with cooling at 0°C. The reaction mixture was stirred for 1 hour at 0°C. The reaction mixture was poured over a mixture of water and ice and 6M sodium hydroxide was used to bring the pH to alkaline. Then the solution was extracted with a mixture of (1/1) benzene/ether. The organic layer was dried over sodium sulfate, filtered and was evaporated to dryness to give 6.16g of 2-(2,5-dimethoxy-4-nitrophenyl) ethanamine 4 as dark brown crude oil used in the next step without any further purification. With sodium hydroxide in water, acetic acid, benzene Patent; Randox Laboratories Ltd.; Benchikh, Elouard; Fitzgerald, Peter; McConnell, Ivan; Lowry, Philip; EP2835648; (2015); (A1) English View in Reaxys 3 : Example 3 Example 3 Preparation 2-(2, 5-dimethoxy-4-nitrophenyl)ethylamine 4 To a cooled solution of 2-(2, 5-dimethoxyphenyl)ethylamine 3 (12.0 g, 0.066 mol) in acetic acid (200 ml) was added nitric acid (40 ml) and the solution was stirred at 0 °C for 1 hour. The mixture was poured into a mixture of ice and water. The mixture was then made strongly alkaline with 6 M NaOH. The basic solution was extracted with a mixture of benzene/ether (1/1) (2x 200 ml). The organic layers were washed by water (100 ml) and brine (100 ml), dried over Na2SO4 and filtered. The filtrate was concentrated to dryness under vacuum to give 11.2 g of 2-(2, 5-dimethoxy-4-nitrophenyl)ethanamine 4 as a brown dark oil (crude) used in the next step without any further purification.

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With nitric acid in acetic acid, Time= 1h, T= 0 °C Patent; Randox Laboratories Ltd.; Benchik, Elouard; Fitzgerald, Peter; Lowry, Philip; McConnell, Ivan; EP2950104; (2015); (A1) English View in Reaxys

O O

H 2N

Rx-ID: 25909427 View in Reaxys 3/177 Yield

Conditions & References

60 %

40 :420 mg (0.556 mmol) of PS-carbodiimide resin are conditioned in 4 ml of dichloromethane. After 10 minutes of agitation, the resin is filtered and then rinsed 3 times with 4 ml of dichloromethane. 4 ml of dichloromethane and 4 ml of tetrahydrofurane (THF) are added, and then 100 mg (0.278 mmol) of acid obtained according to preparation IV, 33.5 mg (0.185 mmol) of 2,5-dimethoxybenzeneethanamine and 3.8 mg (0.019 mmol) of HOAT are introduced in succession. The reaction medium is then agitated at ambient temperature. After 16 hours of agitation, 0.278 mmol of IRA400 resin are introduced into the reaction medium and then, after 2 hours of agitation, 0.278 mmol of isocyanate resin. After 1 hour of agitation, the reaction medium is filtered and then the resins are washed 3 times with 3 ml of dichloromethane. The filtrates collected are concentrated and then dried under reduced pressure. In this way the expected compound is obtained in the form of a colorless oil (yield=60percent). NMR 1H (DMSO, 300 MHz) δ: 8.14 (t, 1H, NHCO), 7.69 (d, 2H, Harom.), 7.55 (d, 2H, Harom.), 7.44 (d, 1H, Harom.), 7.21 (t, 1H, Harom.), 7.10 (d, 1H, Harom.), 7.00 (t, 1H, Harom.), 6.87 (d, 1H, Harom.), 6.74 (m, 2H, Harom.), 4.69 (dd, 1H, NCHCO), 3.73 (s, 3H, OCH3), 3.68 (s, 3H, OCH3), 3.29 (m, 2H, CH2NCO), 3.05 (dd, 1H, CH2CHCO), 2.84 (dd, 1H, CH2CHCO), 2.69 (m, 2H, CH2Ph), 1.25 (s, 9H, tBu). MS (ESI+) m/z 523 (MH+). With 1-hydroxy-7-aza-benzotriazole in tetrahydrofuran, dichloromethane Solid phase= Polystyrene, Time= 16h, T= 20 °C Patent; Laboratoires Fournier S.A.; US2007/99960; (2007); (A1) English View in Reaxys

O N

H 2N

Rx-ID: 23498139 View in Reaxys 4/177 Yield 38 %

Conditions & References 5.1.10 :INTERMEDIATE 5.1. 10: 4-(5,8-DIMETHOXY-1,2,3, 4- TETRAHYDROISOQUINOLIN-1-YL)-N, N-DIETHYLBENZAMIDE; INTERMEDIATE 3.1. 1 (100 mg, 0.49 mmol) and 2,5-dimethoxyphenethylamine (0. 09 mL, 0.54 mmol) were dissolved in methanol (2 mL) and stirred at room temperature for 18 h. The solvent was removed in vacuo and the residue was redissolved in TFA (1.5 mL). The reaction mixture was refluxed for 3 d and afterwards concentrated in vacuo and redissolved in DCM. The organic phase was washed with saturated aqueous sodium bicarbonate solution, water, and brine, dried, and concentrated in vacuo. The resulting syrup was purified by flash chromatography to yield a foam (68 mg, 0.185 mmol, 38percent). 1H NMR (500 MHz, CDC13) : b 1.12, 1.24 (2 brs, 6H), 2.82-3. 20 (m, 4H), 3.28, 3.55 (2 brs, 4H), 3.53, 3.84 (2 s, 6H), 5.59 (s, 1H), 6.67, 6.78 (2 d, J 9 Hz, 2H), 7.26, 7.32 (2 d, J 8 Hz, 4H). 13C NMR (125 MHz, CDC13) : 6 14. 2,15. 5,22. 2,37. 1,39. 7,43. 8,54. 5, 55. 8, 55. 9,108. 3,109. 1,124. 0, 124.9, 136. 7,126. 6,129. 1,150. 5,151. 4,171. 3. (+) LRESIMS mlz 369 [M+H] +. Stage 1: in methanol, Time= 18h, T= 20 °C Stage 2: With trifluoroacetic acid, Time= 72h, Heating / reflux Stage 3: With sodium hydrogencarbonate in dichloromethane, water Patent; ASTRAZENECA AB; WO2005/61484; (2005); (A1) English View in Reaxys

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O O

O O S HN

H 2N

Rx-ID: 23841221 View in Reaxys 5/177 Yield

Conditions & References

94 %

1.1 :Example 1 Thioacetic acid S-(2-{4-[2-(2,5-dimethoxy-phenyl)-ethylsulfainoyl]-phenyl}-2-oxo-ethyI) ester:Step 1 4-Acetyl-JV-[2-(2,5-dimethoxy-phenyl)-ethyl]-benzenesulfonamide: To a solution of the amine (0.878 g, 4.84 mmol) in THF (8 mL) was added pyridine (1.174 ml, 14.5 mmol). 4-Acetyl-benzenesulfonyl chloride (1.112 g, 5.05 mmol) was then added as a solid, and the resulting dark solution was stirred for 10 min. Volatiles were removed in vacuo and the resulting residue was suspended in THF. Excess Et3N was added and the mixture was stirred for several minutes before the solids were filtered. The mother liquor EPO <DP n="33"/>was evaporated to a solid which was recrystalized in ethyl acetate and hexanes to yield the desired compound (1.65 g, 94percent). LC-MS (ES+): 364 [MH]+ m/e. Stage 1: With pyridine in tetrahydrofuran, Time= 0.166667h Stage 2: With triethylamine in tetrahydrofuran Patent; KALYPSYS, INC.; WO2006/63294; (2006); (A2) English View in Reaxys

N O

H 2N

Rx-ID: 363363 View in Reaxys 6/177 Yield 76 %

Conditions & References With lithium aluminium tetrahydride in tetrahydrofuran, Heating Cheng; Castagnoli Jr.; Journal of Medicinal Chemistry; vol. 27; nb. 4; (1984); p. 513 - 520 View in Reaxys With hydrochlorid acid, ethanol, acetic acid, bei der Reduktion an Blei-Elektroden Sugasawa; Shigehara; Chemische Berichte; vol. 74; (1941); p. 459,462 View in Reaxys With lithium aluminium tetrahydride, diethyl ether, T= 170 °C Cromartie; Harley-Mason; Journal of the Chemical Society; (1952); p. 2525 View in Reaxys Govindachari; Lakshmikantham; Proceedings - Indian Academy of Sciences, Section A; vol. <A> 46; (1957); p. 406,408 View in Reaxys With lithium aluminium tetrahydride in diethyl ether, benzene Khafagy,E.Z.; Lambooy,J.P.; Journal of Medicinal Chemistry; vol. 9; (1966); p. 936 - 940 View in Reaxys 2 : Example 2 Example 2 Preparation of 2-(2,5-dimethoxyphenyl)ethanamine 3 Lithium aluminum hydride (LiAlH4) (5.38g, 0.14mol) was added portion-wise to anhydrous tetrahydrofuran (250ml) and then (E)-1,4-dimethoxy-2-(2-nitrovinyl) benzene 2 (9.87g, 0.047mol) dissolved in anhydrous tetrahydrofuran (150ml) was added drop-wise. The reaction mixture was refluxed for 4 hours then stirred at room temperature overnight. To quench the reaction mixture, water (5ml) followed by 1 M sodium hydroxide (5ml) and then water (15ml) were added slowly while cooling. The resulting mixture was then stirred at room temperature and the white precipitate which formed was removed by filtration through a celite plug and washed with Et2O.

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The solvent was removed under vacuo to give 5.76g of 2-(2,5-dimethoxyphenyl) ethanamine 3 crude as yellow oil. With sodium hydroxide in tetrahydrofuran, water Patent; Randox Laboratories Ltd.; Benchikh, Elouard; Fitzgerald, Peter; McConnell, Ivan; Lowry, Philip; EP2835648; (2015); (A1) English View in Reaxys 12.5 g

2 : Example 2 Example 2 Preparation of 2-(2, 5-dimethoxyphenyl)ethylamine 3 To lithium aluminium hydride (10.32 g, 0.27 mol) was added anhydrous THF (300 ml). A solution of 1-(2, 5-dimethoxyphenyl)nitroethane 2 (20.0 g, 0.956 mol) in THF (150 ml) was added drop-wise over a period of 45 min. The mixture was heated at reflux for 4 hours, after which thin-layer chromatography (TLC) analysis showed absence of starting material. After cooling at room temperature the reaction was quenched by the stepwise addition of 50percent THF/H2O (10 ml), 15percent NaOH solution and H2O (30 ml). The precipitate solids were removed by vacuum filtration, and the filtrate was reduced under vacuum to afford a yellow oil. The oil was dissolved in Et2O washed with H2O (2x 100 ml) and then extracted into 1 M HCl (2x 200 ml). The acidic extracts were washed with Et2O (2x 75 ml) and then made strongly basic with 5 M NaOH. The basic solution was extracted with Et2O (3x 150 ml). The ether extract was washed with water (2x 100 ml), and brine (100 ml) dried over Na2SO4 and filtered. The filtrate was concentrated to dryness to provide 12.5 g of 2-(2, 5-dimethoxyphenyl)ethylamine 3 as a clear oil. With lithium aluminium tetrahydride, sodium hydroxide in tetrahydrofuran, Time= 4.75h, Reflux Patent; Randox Laboratories Ltd.; Benchik, Elouard; Fitzgerald, Peter; Lowry, Philip; McConnell, Ivan; EP2950104; (2015); (A1) English View in Reaxys

O O N

H 2N

Rx-ID: 2148479 View in Reaxys 7/177 Yield 31 %

Conditions & References With sodium tetrahydroborate, boron trifluoride diethyl etherate in tetrahydrofuran, Time= 4h, Heating Montgomery; Buon; Eibauer; Guiry; Keenan; McBean; British Journal of Pharmacology; vol. 152; nb. 7; (2007); p. 1121 - 1130 View in Reaxys With lithium aluminium tetrahydride, sulfuric acid in tetrahydrofuran, Time= 24h, Ambient temperature Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, Time= 4h, Ambient temperature Kubo, Akinori; Saito, Naoki; Kawakami, Nanko; Matsuyama, Yasuo; Miwa, Teruyo; Synthesis; nb. 9; (1987); p. 824 - 827 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, Time= 2h, Heating Cantrell, Amanda S.; Engelhardt, Per; Hoegberg, Marita; Jaskunas, S. Richard; Johansson, Nils Gunnar; Jordan, Christopher L.; Kangasmetsae, Jussi; Kinnick, Michael D.; Lind, Peter; Morin Jr., John M.; Muesing; Noreen, Rolf; Oeberg, Bo; Pranc, Paul; Sahlberg, Christer; Ternansky, Robert J.; Vasileff, Robert T.; Vrang, Lotta; West, Sarah J.; Zhang, Hong; Journal of Medicinal Chemistry; vol. 39; nb. 21; (1996); p. 4261 - 4274

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View in Reaxys 2 : Preparation of 2-(2,5-dimethoxyphenyl)ethanamine 3 Example 2 Preparation of 2-(2,5-dimethoxyphenyl)ethanamine 3 Lithium aluminum hydride (LAIN (5.38 g, 0.14 mol) was added portion-wise to anhydrous tetrahydrofuran (250 ml) and then (E)-1,4-dimethoxy-2-(2-nitrovinyl)benzene 2 (9.87 g, 0.047 mol) dissolved in anhydrous tetrahydrofuran (150 ml) was added drop-wise. The reaction mixture was refluxed for 4 hours then stirred at room temperature overnight. To quench the reaction mixture, water (5 ml) followed by 1M sodium hydroxide (5 ml) and then water (15 ml) were added slowly while cooling. The resulting mixture was then stirred at room temperature and the white precipitate which formed was removed by filtration through a celite plug and washed with Et2O. The solvent was removed under vacuo to give 5.76 g of 2-(2,5-dimethoxyphenyl) ethanamine 3 crude as yellow oil. With sodium hydroxide in tetrahydrofuran, water Patent; Benchikh, Elouard; Fitzgerald, Peter; McConnell, Ivan; Lowry, Philip; US2015/38366; (2015); (A1) English View in Reaxys

N O

F O

H 2N

Rx-ID: 4763439 View in Reaxys 8/177 Yield 100 %

Conditions & References With N,N-diethyl-N-isopropylamine, benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate in N,N-dimethyl-formamide, Time= 16h, T= 25 °C Boger, Dale L.; Ozer, Rachel S.; Andersson, Carl-Magnus; Bioorganic and Medicinal Chemistry Letters; vol. 7; nb. 14; (1997); p. 1903 - 1908 View in Reaxys

100 %

65 %

With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate, N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide, T= 25 °C , Acylation Boger, Dale L.; Chai, Wenying; Tetrahedron; vol. 54; nb. 16; (1998); p. 3955 - 3970 View in Reaxys With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate, N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide, Time= 16h, T= 25 °C Boger, Dale L.; Ducray, Pierre; Chai, Wenying; Jiang, Weiqin; Goldberg, Joel; Bioorganic and Medicinal Chemistry Letters; vol. 8; nb. 17; (1998); p. 2339 - 2344 View in Reaxys

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H N

O O

N O

O O

H 2N

Rx-ID: 4763441 View in Reaxys 9/177 Yield

Conditions & References

100 %

95 %

87 %

O O

N O

H 2N

Rx-ID: 4763437 View in Reaxys 10/177 Yield 90 %

89 %

With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate, N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide, Time= 16h, T= 25 °C , Substitution

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Boger, Dale L.; Goldberg, Joel; Jiang, Weiqin; Chai, Wenying; Ducray, Pierre; Lee, Jae Kyoo; Ozer, Rachel S.; Andersson, Carl-Magnus; Bioorganic and Medicinal Chemistry; vol. 6; nb. 8; (1998); p. 1347 - 1378 View in Reaxys With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate, N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide, Time= 16h, T= 25 °C Boger, Dale L.; Ducray, Pierre; Chai, Wenying; Jiang, Weiqin; Goldberg, Joel; Bioorganic and Medicinal Chemistry Letters; vol. 8; nb. 17; (1998); p. 2339 - 2344 View in Reaxys

HO O

O O

N O

H 2N

Rx-ID: 4763440 View in Reaxys 11/177 Yield

Conditions & References

85 %

With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate, N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide, Time= 16h, T= 25 °C , Substitution Boger, Dale L.; Goldberg, Joel; Jiang, Weiqin; Chai, Wenying; Ducray, Pierre; Lee, Jae Kyoo; Ozer, Rachel S.; Andersson, Carl-Magnus; Bioorganic and Medicinal Chemistry; vol. 6; nb. 8; (1998); p. 1347 - 1378 View in Reaxys With N,N-diethyl-N-isopropylamine, benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate in N,N-dimethyl-formamide, Time= 16h, T= 25 °C Boger, Dale L.; Ozer, Rachel S.; Andersson, Carl-Magnus; Bioorganic and Medicinal Chemistry Letters; vol. 7; nb. 14; (1997); p. 1903 - 1908 View in Reaxys With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate, N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide, Time= 16h, T= 25 °C Boger, Dale L.; Ducray, Pierre; Chai, Wenying; Jiang, Weiqin; Goldberg, Joel; Bioorganic and Medicinal Chemistry Letters; vol. 8; nb. 17; (1998); p. 2339 - 2344 View in Reaxys

O HN

O HO

O H N

O O

O NH

H 2N

Rx-ID: 4763442 View in Reaxys 12/177 Yield 100 %

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View in Reaxys 75 %

With N,N-diethyl-N-isopropylamine, benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate in N,N-dimethyl-formamide, Time= 16h, T= 25 °C Boger, Dale L.; Ozer, Rachel S.; Andersson, Carl-Magnus; Bioorganic and Medicinal Chemistry Letters; vol. 7; nb. 14; (1997); p. 1903 - 1908 View in Reaxys With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate, N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide, Time= 16h, T= 25 °C Boger, Dale L.; Ducray, Pierre; Chai, Wenying; Jiang, Weiqin; Goldberg, Joel; Bioorganic and Medicinal Chemistry Letters; vol. 8; nb. 17; (1998); p. 2339 - 2344 View in Reaxys

H 2N

O NH O

Rx-ID: 4763438 View in Reaxys 13/177 Yield

Conditions & References

81 %

76 %

O O O

NH O O

O O

H 2N HO

O O

N O

N H

O O

O HN

O NH

O O

Rx-ID: 5050296 View in Reaxys 14/177

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Yield

Conditions & References

76 %

55 %

H 2N

H N O

Rx-ID: 9942267 View in Reaxys 15/177 Yield

Conditions & References

91 %

With 4-(N,N-dimethlyamino)pyridine, triethylamine in dichloromethane, Time= 48h Dothager, Robin S.; Putt, Karson S.; Allen, Brittany J.; Leslie, Benjamin J.; Nesterenko, Vitaliy; Hergenrother, Paul J.; Journal of the American Chemical Society; vol. 127; nb. 24; (2005); p. 8686 - 8696 View in Reaxys

O O

N O

O H 2N

Rx-ID: 5190446 View in Reaxys 16/177 Yield 100 %

Conditions & References With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate, N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide, Time= 16h, T= 25 °C , Substitution Boger, Dale L.; Goldberg, Joel; Jiang, Weiqin; Chai, Wenying; Ducray, Pierre; Lee, Jae Kyoo; Ozer, Rachel S.; Andersson, Carl-Magnus; Bioorganic and Medicinal Chemistry; vol. 6; nb. 8; (1998); p. 1347 - 1378 View in Reaxys With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate, N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide, Time= 16h, T= 25 °C Boger, Dale L.; Ducray, Pierre; Chai, Wenying; Jiang, Weiqin; Goldberg, Joel; Bioorganic and Medicinal Chemistry Letters; vol. 8; nb. 17; (1998); p. 2339 - 2344 View in Reaxys

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O N H

H 2N

Rx-ID: 9942268 View in Reaxys 17/177 Yield

Conditions & References

76 %

O H N

O O

NH O

O H 2N

Rx-ID: 28113194 View in Reaxys 18/177 Yield

Conditions & References 270 : EXAMPLE 270; Ethyl 7-(3-aminopyrrolidin-1-yl)-1-(2-(2,5-dimethoxyphenyl)ethyl)-6-fluoro-5-methyl-4oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate A solution of EXAMPLE 1C (347.3 mg) in acetonitrile (9.9 mL) was treated with 2,5-dimethoxyphenethylamine (0.17 mL), stirred for 2 hours at 25° C. and 16 hours at 50° C. and cooled, treated with potassium carbonate (363.5 mg), heated for 2 days at 85° C. and cooled, treated with tert-butyl pyrrolidin-3-ylcarbamate (277.1 mg), stirred for 2 days at 25° C., and concentrated. A solution of the concentrate in tetrahydrofuran (8 mL) and 4N HCl/dioxane (16 mL) at 25° C. was stirred for 2 hours, treated with diethyl ether, centrifuged, and triturated with diethyl ether. The solid was extracted with methanol and dichloromethane, and the supernate was concentrated. The concentrate was purified by reverse phase high performance liquid chromatography (HPLC) on a C8 column with 0percent-100percent acetonitrile in water containing 0.1percent trifluoroacetic acid. NMR (300 MHz, DMSO-d6) δ ppm 8.12 (s, 1H), 8.10 (bs, 3H), 6.78 (m, 3H), 4.44 (dd, 2H), 4.13 (q, 2H), 4.00 (m, 2H), 3.87 (m, 3H), 3.65 (s, 3H), 3.59 (s, 3H), 3.00 (dd, 2H), 2.66 (d, 3H), 2.33 (m, 1H), 2.12 (m, 1H), 1.21 (t, 3H) Stage 1: With N-ethyl-N,N-diisopropylamine in acetonitrile, Time= 18h, T= 25 - 50 °C Stage 2: With potassium carbonate in acetonitrile, Time= 48h, T= 85 °C Stage 3: in acetonitrile, Time= 48h, T= 25 °C Patent; Anderson, David; Beutel, Bruce; Bosse, Todd D.; Clark, Richard; Cooper, Curt; Dandliker, Peter; David, Caroline; Gu, Yu-Gui; Hansen, Todd Matthew; Hinman, Mira; Kalvin, Douglas; Larson, Daniel P.; Lynch, Linda; Ma, Zhenkun; Motter, Christopher; Palazzo, Fabio; Rosenberg, Teresa; Rehm, Tamara; Sanders, William; Tufano, Michael; Wagner, Rolf; Weitzberg, Moshe; Yong, Hong; Zhang, Tianyuan; US2003/232818; (2003); (A1) English View in Reaxys

H 2N OH

H 2N

Rx-ID: 145366 View in Reaxys 19/177 Yield

Conditions & References With hydrogenchloride, T= 170 °C Baltzly et al.; Journal of the American Chemical Society; vol. 72; (1950); p. 382 View in Reaxys

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With hydrogen bromide, auf Siedetemperatur Cromartie; Harley-Mason; Journal of the Chemical Society; (1952); p. 2525 View in Reaxys With hydrogen iodide Leaf; Neuberger; Biochemical Journal; vol. 43; (1948); p. 606,608; Biochemical Journal; vol. 57; (1954); p. 528 View in Reaxys With boron tribromide in dichloromethane, Time= 48h, Ambient temperature Cheng; Castagnoli Jr.; Journal of Medicinal Chemistry; vol. 27; nb. 4; (1984); p. 513 - 520 View in Reaxys

N+ Br–

I O

H 2N

Rx-ID: 9744377 View in Reaxys 20/177 Yield

Conditions & References

75 %

Stage 1: in chloroform, Time= 3h, T= 40 °C Stage 2: With boron tribromide in dichloromethane Genady, Afaf R.; El-Zaria, Mohamed E.; Gabel, Detlef; Journal of Organometallic Chemistry; vol. 689; nb. 20; (2004); p. 3242 - 3250 View in Reaxys

H N

Pol

(v1)

Pol

(v1)

H 2N

Rx-ID: 23322578 View in Reaxys 21/177 Yield

Conditions & References 4 :To a solution of the compound prepared in Reference example 3 in N-methyl-2-pyrrolidone (100 ml) wasadded 2,5-dimethoxyphenethylamine (9.60 g). The mixture was stirred at room temperateure for 26 hours. The resinwas filtered off from the reaction mixture and washed with N-methyl-2-pyrrolidone (100 ml x 3) and methylene chloride(100 ml x 4). The obtained resin was dried under reduced pressure to give polymer-supported 3-(2-(2,5-dimethoxyphe-nyl)ethyl)aminopropanoic acid ester (13.70 g). in 1-methyl-pyrrolidin-2-one Solid phase= polystyrene-supported Wang resin, Time= 26h, T= 20 °C Patent; ONO PHARMACEUTICAL CO., LTD.; EP1533294; (2005); (A1) English View in Reaxys

H O

H 2N

Rx-ID: 29162776 View in Reaxys 22/177 Yield

Conditions & References 68 : Production Example 68 Production Example 68 Under an argon atmosphere, a solution of 2,5-dimethoxyphenethylamine (3.175 g) in benzene (4 mL) was added with stirring to a suspension of benzaldehyde (1.86 g) and magnesium sulfate (3.89 g) in benzene (10 mL). An exothermic reaction took place, followed by further stirring overnight.

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After the reaction was complete, the reaction liquid was filtered and the filtrate was concentrated under reduced pressure to obtain 2-(2,5-dimethoxyphenyl)-N-[(1E)-phenylmethylene]ethanamine (4,72 g). With magnesium sulfate in benzene, Inert atmosphere Patent; Astellas Pharma Inc.; EP2149560; (2010); (A1) English View in Reaxys

HO O

H 2N

Rx-ID: 39258115 View in Reaxys 23/177 Yield

Conditions & References General procedure for the preparation of N-benzylated 2-arylethanamine hydrochlorides. General procedure: The appropriate amine (5.5 mmol) andaldehyde (6.0 mmol) were dissolved in MeOH (90 mL) and stirred overnight at room temperature. Powdered NaBH4 (24 mmol) was then added in small portions, with good stirring, over approximately 30 min, and the reaction was allowed to proceed for 24 h. The solvent was removed in a rotary evaporator and the cream-colored to light yellow residue was taken up with CH2Cl2 (50mL) and washed with saturated aqueous NaHCO3 solution. The organic phase was dried (Na2SO4), filtered, and concentrated to dryness. The light yellow oil was dissolved in 2-propanol (5 mL) to which was added 37percent HCl (540 mL),and the solution was diluted with Et2O (100 mL) to afford the salt, usually as a white crystalline powder. in methanol, T= 20 °C Tirapegui, Cristian; Toro-Sazo, Miguel A.; Cassels, Bruce K.; Journal of the Chilean Chemical Society; vol. 59; nb. 3; (2014); p. 2625 - 2627 View in Reaxys

O O

H 2N

Rx-ID: 39258122 View in Reaxys 24/177 Yield

H N

O H 2N

N O

Rx-ID: 2345066 View in Reaxys 25/177

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Yield

Conditions & References

80 %

With nitric acid, acetic acid, Time= 1h, T= 0 °C Cheng; Castagnoli Jr.; Journal of Medicinal Chemistry; vol. 27; nb. 4; (1984); p. 513 - 520 View in Reaxys

Cl O

H N

O O

H 2N

Rx-ID: 4258535 View in Reaxys 26/177 Yield

Conditions & References

81 %

With triethylamine in dichloromethane, Time= 0.5h, Ambient temperature Langlois, Michel; Bremont, Beatrice; Shen, Shuren; Poncet, Annie; Andrieux, Jean; et al.; Journal of Medicinal Chemistry; vol. 38; nb. 12; (1995); p. 2050 - 2060 View in Reaxys

H N

O O

H 2N

Rx-ID: 4262655 View in Reaxys 27/177 Yield

Conditions & References

84 %

F O

O O

H N

O NH 2

H 2N

NH 2

Rx-ID: 10281930 View in Reaxys 28/177 Yield

Conditions & References

79 %

in dimethyl sulfoxide, Time= 0.5h, T= 110 °C , microwave irradiation Szczepankiewicz, Bruce G.; Kosogof, Christi; Nelson, Lissa T. J.; Liu, Gang; Liu, Bo; Zhao, Hongyu; Serby, Michael D.; Xin, Zhili; Liu, Mei; Gum, Rebecca J.; Haasch, Deanna L.; Wang, Sanyi; Clampit, Jill E.; Johnson, Eric F.; Lubben, Thomas H.; Stashko, Michael A.; Olejniczak, Edward T.; Sun, Chaohong; Dorwin, Sarah A.; Haskins, Kristi; Abad-Zapatero, Cele; Fry, Elizabeth H.; Hutchins, Charles W.; Sham, Hing L.; Rondinone, Cristina M.; Trevillyan, James M.; Journal of Medicinal Chemistry; vol. 49; nb. 12; (2006); p. 3563 - 3580 View in Reaxys

H N

Cl O

O O

H 2N

Rx-ID: 4265448 View in Reaxys 29/177 Yield 68 %

Conditions & References With triethylamine in dichloromethane, Time= 0.5h, Ambient temperature

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Langlois, Michel; Bremont, Beatrice; Shen, Shuren; Poncet, Annie; Andrieux, Jean; et al.; Journal of Medicinal Chemistry; vol. 38; nb. 12; (1995); p. 2050 - 2060 View in Reaxys

H N

H 2N

Rx-ID: 4268448 View in Reaxys 30/177 Yield

Conditions & References

69 %

4-formyl-3,5-dimethoxyphenoxy-Merrifield resin

H N

O O

H 2N

Rx-ID: 8520454 View in Reaxys 31/177 Yield

Conditions & References

50 %

Stage 1: With sodium tris(acetoxy)borohydride in acetic acid, N,N-dimethyl-formamide, Time= 69h, T= 20 °C , Solid phase reaction, reductive amination Stage 2: With benzotriazol-1-ol, dicyclohexyl-carbodiimide in N,N-dimethyl-formamide, Time= 15h, T= 20 °C , Solid phase reaction, acylation Stage 3: With dimethylsulfide, water, trifluoroacetic acid in dichloromethane, Time= 15h, T= 20 °C , Solid phase reaction, cleavage of amide Pegurier, C.Ecile; Curtet, Sophie; Nicolas, Jean-Paul; Boutin, Jean A.; Delagrange, Philippe; Renard, Pierre; Langlois, Michel; Bioorganic and Medicinal Chemistry; vol. 8; nb. 1; (2000); p. 163 - 171 View in Reaxys

H N

O HO

4-formyl-3,5-dimethoxyphenoxy-Merrifield resin O

O O

H 2N

Rx-ID: 8531007 View in Reaxys 32/177 Yield 48 %

Conditions & References Stage 1: With sodium tris(acetoxy)borohydride in acetic acid, N,N-dimethyl-formamide, Time= 69h, T= 20 °C , Solid phase reaction, reductive amination Stage 2: With benzotriazol-1-ol, dicyclohexyl-carbodiimide in N,N-dimethyl-formamide, Time= 15h, T= 20 °C , Solid phase reaction, acylation Stage 3: With dimethylsulfide, water, trifluoroacetic acid in dichloromethane, Time= 15h, T= 20 °C , Solid phase reaction, cleavage of amide Pegurier, C.Ecile; Curtet, Sophie; Nicolas, Jean-Paul; Boutin, Jean A.; Delagrange, Philippe; Renard, Pierre; Langlois, Michel; Bioorganic and Medicinal Chemistry; vol. 8; nb. 1; (2000); p. 163 - 171 View in Reaxys

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H 13C O

13C

C H

13C

HCl

13C

C H

H 2N

13C

HCl

H 2N

Rx-ID: 38014846 View in Reaxys 33/177 Yield

Conditions & References

57 %

Stage 1: With bromine in acetic acid, Time= 16.5h, T= 22 °C Stage 2: With hydrogenchloride in diethyl ether, isopropyl alcohol, 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 OH

H 2N

Rx-ID: 8614329 View in Reaxys 34/177 Yield

Conditions & References

92 %

Stage 1: With N-hydroxysuccinimidyl polystyrene resin, triethylamine, diisopropyl-carbodiimide in dichloromethane, Time= 4h, Solid phase reaction Stage 2: in dichloromethane, Time= 0.333333h, Acylation Shao, Hui; Zhang, Qiang; Goodnow, Robert; Chen, Li; Tam, Steve; Tetrahedron Letters; vol. 41; nb. 22; (2000); p. 4257 - 4260 View in Reaxys

OH N

OH NH 2

O– O

H 2N O

Rx-ID: 9642252 View in Reaxys 35/177 Yield

Conditions & References

20 %

With N(Et)4ClO4 in methanol, T= 20 °C , Electrochemical reaction Blattes, Estelle; Fleury, Maurice-Bernard; Largeron, Martine; Journal of Organic Chemistry; vol. 69; nb. 3; (2004); p. 882 - 890 View in Reaxys

O O

Cl O

H N

O O

H 2N

Rx-ID: 9808010 View in Reaxys 36/177 Yield 61 %

Conditions & References With potassium carbonate in diethyl ether, Time= 1.5h, T= 0 °C Tietze, Lutz F.; Rackelmann, Nils; Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences; vol. 59; nb. 4; (2004); p. 468 - 477

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View in Reaxys

O O

HN O

H 2N

Rx-ID: 8629212 View in Reaxys 37/177 Yield

Conditions & References

77 %

NH 2 O

H 2N

Rx-ID: 15585980 View in Reaxys 38/177 Yield

Conditions & References Reaction Steps: 4 1: 92 percent / 0 °C 2: 18 percent / TiCl4 / CH2Cl2 / -30 - 20 °C 3: 79 percent / H2; AcOH; 70 percent HClO4 / 10 percent Pd/C / 6 h / 3102.89 Torr 4: 15 percent aq. NaOH / methanol / 2 h / Heating With sodium hydroxide, perchloric acid, hydrogen, titanium tetrachloride, acetic acid, palladium on activated charcoal in methanol, dichloromethane, 1: Acetylation / 2: Friedel-Crafts acylation / 3: Reduction / 4: Hydrolysis Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p. 3074 - 3084 View in Reaxys

O O

NH 2 O

H 2N

Rx-ID: 15585981 View in Reaxys 39/177 Yield

Conditions & References Reaction Steps: 4 1: 92 percent / 0 °C 2: 31 percent / TiCl4 / CH2Cl2 / -30 - 20 °C 3: 43 percent / H2; AcOH; 70 percent HClO4 / 10 percent Pd/C / 6 h / 3102.89 Torr 4: 15 percent aq. NaOH / methanol / 2 h / Heating With sodium hydroxide, perchloric acid, hydrogen, titanium tetrachloride, acetic acid, palladium on activated charcoal in methanol, dichloromethane, 1: Acetylation / 2: Friedel-Crafts acylation / 3: Reduction / 4: Hydrolysis

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Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p. 3074 - 3084 View in Reaxys

NH 2

H 2N

Rx-ID: 15585982 View in Reaxys 40/177 Yield

Conditions & References Reaction Steps: 5 1: 92 percent / 0 °C 2: 58 percent / ICl; NaI; 0.1 N NaOH / acetic acid / 20 °C 3: 65 percent / pyridine / 120 °C 4: 65 percent / H2 / 10 percent Pd/C / methanol / 4 h / 2068.59 Torr 5: 15 percent aq. NaOH / methanol / 2 h / Heating With pyridine, sodium hydroxide, hydrogen, iodine cloride, sodium iodide, palladium on activated charcoal in methanol, acetic acid, 1: Acetylation / 2: Iodination / 3: Substitution / 4: Catalytic hydrogenation / 5: Hydrolysis Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p. 3074 - 3084 View in Reaxys

O F

O H 2N

N H

Rx-ID: 15585983 View in Reaxys 41/177 Yield

Conditions & References Reaction Steps: 3 1: 92 percent / 0 °C 2: 18 percent / TiCl4 / CH2Cl2 / -30 - 20 °C 3: 79 percent / H2; AcOH; 70 percent HClO4 / 10 percent Pd/C / 6 h / 3102.89 Torr With perchloric acid, hydrogen, titanium tetrachloride, acetic acid, palladium on activated charcoal in dichloromethane, 1: Acetylation / 2: Friedel-Crafts acylation / 3: Reduction Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p. 3074 - 3084 View in Reaxys

F O

F HN

O H 2N

Rx-ID: 15585985 View in Reaxys 42/177 Yield

Conditions & References Reaction Steps: 3 1: 92 percent / 0 °C 2: 31 percent / TiCl4 / CH2Cl2 / -30 - 20 °C 3: 43 percent / H2; AcOH; 70 percent HClO4 / 10 percent Pd/C / 6 h / 3102.89 Torr With perchloric acid, hydrogen, titanium tetrachloride, acetic acid, palladium on activated charcoal in dichloromethane, 1: Acetylation / 2: Friedel-Crafts acylation / 3: Reduction

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Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p. 3074 - 3084 View in Reaxys

F O

F HN

O H 2N O

Rx-ID: 15585987 View in Reaxys 43/177 Yield

Conditions & References Reaction Steps: 4 1: 92 percent / 0 °C 2: 58 percent / ICl; NaI; 0.1 N NaOH / acetic acid / 20 °C 3: 65 percent / pyridine / 120 °C 4: 65 percent / H2 / 10 percent Pd/C / methanol / 4 h / 2068.59 Torr With pyridine, sodium hydroxide, hydrogen, iodine cloride, sodium iodide, palladium on activated charcoal in methanol, acetic acid, 1: Acetylation / 2: Iodination / 3: Substitution / 4: Catalytic hydrogenation Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p. 3074 - 3084 View in Reaxys

O O

N O

H 2N

Rx-ID: 95826 View in Reaxys 44/177 Yield

Conditions & References With formic acid, water, T= 125 °C Baltzly; Buck; Journal of the American Chemical Society; vol. 62; (1940); p. 160,162 View in Reaxys

N O

N H

H 2N

Rx-ID: 8635667 View in Reaxys 45/177 Yield

Conditions & References

74 %

H 2N

Rx-ID: 8663082 View in Reaxys 46/177

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Yield

Conditions & References

68 %

H N

F O

H 2N

Rx-ID: 8706336 View in Reaxys 47/177 Yield

Conditions & References

92 %

T= 0 °C , Acetylation Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p. 3074 - 3084 View in Reaxys

O O

N+

–C

N S

H 2N

Rx-ID: 34501806 View in Reaxys 48/177 Yield

Conditions & References

58 %

Stage 1: in toluene, Time= 0.166667h, T= 80 °C , Sealed tube, Microwave irradiation Stage 2: With scandium tris(trifluoromethanesulfonate) in toluene, Time= 0.166667h, T= 80 °C , Sealed tube, Microwave irradiation Stage 3:Further stages Islas-Jacome, Alejandro; Cardenas-Galindo, Luis E.; Jerezano, Alberto V.; Tamariz, Joaquin; Gonzalez-Zamora, Eduardo; Gamez-Montano, Rocio; Synlett; vol. 23; nb. 20; (2012); p. 2951 - 2956 View in Reaxys

O O

H 2N

N O O

Rx-ID: 11289588 View in Reaxys 49/177 Yield 79 %

Conditions & References in toluene, Reflux Selvakumar, Jayaraman; Ramanathan, Chinnasamy Ramaraj; Organic and Biomolecular Chemistry; vol. 9; nb. 22; (2011); p. 7643 - 7646 View in Reaxys T= 130 °C Xu, Ya-Zhu; Chen, Chinpiao; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 49; nb. 13; (2006); p. 1187 - 1200 View in Reaxys

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H 2N O

H 2N

Rx-ID: 3952265 View in Reaxys 50/177 Yield

Conditions & References

1.4 g

With bromine in acetic acid, Ambient temperature Glennon; Dukat; El-Bermawy; Law; De los Angeles; Teitler; King; Herrick-Davis; Journal of Medicinal Chemistry; vol. 37; nb. 13; (1994); p. 1929 - 1935 View in Reaxys

2.00 g

With bromine in acetic acid, Time= 0.0833333h, T= 20 °C Montgomery; Buon; Eibauer; Guiry; Keenan; McBean; British Journal of Pharmacology; vol. 152; nb. 7; (2007); p. 1121 - 1130 View in Reaxys

O O

H 2N

Rx-ID: 17553208 View in Reaxys 51/177 Yield

Conditions & References Reaction Steps: 2 1: 1.) NaOH, 2.) 4N aq. HCl / 1.) H2O, methanol, -3 deg C, 15 min 2: LiAlH4 / tetrahydrofuran / 2 h / Heating With hydrogenchloride, sodium hydroxide, lithium aluminium tetrahydride in tetrahydrofuran Cantrell, Amanda S.; Engelhardt, Per; Hoegberg, Marita; Jaskunas, S. Richard; Johansson, Nils Gunnar; Jordan, Christopher L.; Kangasmetsae, Jussi; Kinnick, Michael D.; Lind, Peter; Morin Jr., John M.; Muesing; Noreen, Rolf; Oeberg, Bo; Pranc, Paul; Sahlberg, Christer; Ternansky, Robert J.; Vasileff, Robert T.; Vrang, Lotta; West, Sarah J.; Zhang, Hong; Journal of Medicinal Chemistry; vol. 39; nb. 21; (1996); p. 4261 - 4274 View in Reaxys Reaction Steps: 4 1: pyridine; piperidine 2: sodium-amalgam 3: ammonia / 220 - 230 °C 4: sodium hypochlorite With piperidine, pyridine, sodium hypochlorite, sodium amalgam, ammonia Buck; Journal of the American Chemical Society; vol. 54; (1932); p. 3661,3662 View in Reaxys

O HO

H 2N

Rx-ID: 21990676 View in Reaxys 52/177 Yield

Conditions & References Reaction Steps: 2 1: ammonia / 220 - 230 °C 2: sodium hypochlorite With sodium hypochlorite, ammonia Buck; Journal of the American Chemical Society; vol. 54; (1932); p. 3661,3662

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View in Reaxys Reaction Steps: 3 1: benzene; sulfuric acid / unter Entfernen des entstehenden Wassers 2: amyl alcohol; hydrazine hydrate 3: beim Erwaermen des hergestellten Azids in Benzol und Erwaermen des Reaktionsprodukts mit wss. Salzsaeure With pentan-1-ol, sulfuric acid, hydrazine hydrate, benzene Leaf; Neuberger; Biochemical Journal; vol. 43; (1948); p. 606,608; Biochemical Journal; vol. 57; (1954); p. 528 View in Reaxys

O O

H 2N

Rx-ID: 21997586 View in Reaxys 53/177 Yield

Conditions & References Reaction Steps: 3 1: sodium-amalgam 2: ammonia / 220 - 230 °C 3: sodium hypochlorite With sodium hypochlorite, sodium amalgam, ammonia Buck; Journal of the American Chemical Society; vol. 54; (1932); p. 3661,3662 View in Reaxys Reaction Steps: 4 1: Raney nickel; aq. NaOH solution / 73550.8 Torr / Hydrogenation 2: benzene; sulfuric acid / unter Entfernen des entstehenden Wassers 3: amyl alcohol; hydrazine hydrate 4: beim Erwaermen des hergestellten Azids in Benzol und Erwaermen des Reaktionsprodukts mit wss. Salzsaeure With sodium hydroxide, pentan-1-ol, sulfuric acid, nickel, hydrazine hydrate, benzene Leaf; Neuberger; Biochemical Journal; vol. 43; (1948); p. 606,608; Biochemical Journal; vol. 57; (1954); p. 528 View in Reaxys

H 2N O

H 2N

Rx-ID: 9385448 View in Reaxys 54/177 Yield

Conditions & References With bromine in acetic acid Acuna-Castillo, Claudio; Villalobos, Claudio; Moya, Pablo R; Saez, Patricio; Cassels, Bruce K; HuidobroToro, J Pablo; British journal of pharmacology; vol. 136; nb. 4; (2002); p. 510 - 519 View in Reaxys With bromine, acetic acid Xu, Ya-Zhu; Chen, Chinpiao; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 49; nb. 13; (2006); p. 1187 - 1200 View in Reaxys

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H 13C O

13C

C H

13C

HCl

13C

C H

H 2N

13C

HCl

H 2N

Rx-ID: 38014847 View in Reaxys 55/177 Yield

Conditions & References

48 %

Stage 1: With iodine, silver sulphate in ethanol, Time= 48h, Inert atmosphere Stage 2: With hydrogenchloride in diethyl ether, isopropyl alcohol, 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 O

H 2N

Rx-ID: 38487406 View in Reaxys 56/177 Yield

Conditions & References

66 %

Stage 1: With ammonium cerium (IV) nitrate in ethanol, Time= 0.5h, Reflux, Hantzsch Dihydropyridine Synthesis Stage 2: in ethanol, Time= 0.5h, Reflux, Hantzsch Dihydropyridine Synthesis Suryavanshi, Padmakar A.; Sridharan, Vellaisamy; Maiti, Swarupananda; Menendez, J. Carlos; Chemistry - A European Journal; vol. 20; nb. 28; (2014); p. 8791 - 8799 View in Reaxys

HN O

H 2N

Rx-ID: 145367 View in Reaxys 57/177 Yield

Conditions & References With benzaldehyde, beim Erwaermen des Kondensationsprodukts mit Methyljodid in Benzol und Erwaermen des Reaktionsprodukts mit wasserhaltigem Aethanol Buck; Journal of the American Chemical Society; vol. 54; (1932); p. 3661,3662 View in Reaxys

H 2N O

O O

H 2N

Rx-ID: 379546 View in Reaxys 58/177 Yield

Conditions & References With sodium hypochlorite Buck; Journal of the American Chemical Society; vol. 54; (1932); p. 3661,3662 View in Reaxys

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E 2

HCl

NH 2 2H

Rx-ID: 11289582 View in Reaxys 59/177 Yield

Conditions & References

43 %

With lithium aluminium tetrahydride in tetrahydrofuran, Time= 24h, Heating Xu, Ya-Zhu; Chen, Chinpiao; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 49; nb. 13; (2006); p. 1187 - 1200 View in Reaxys

O O

O NH

H 2N

Rx-ID: 13168556 View in Reaxys 60/177 Yield

Conditions & References Reaction Steps: 3 1: 61 percent / aq. K2CO3 / diethyl ether / 1.5 h / 0 °C 2: 59 percent / P4O10 / toluene / 1 h / Heating 3: 98 percent / H2; AcOH / Pd/C / ethanol / 1.17 h / 25 °C / 3075.25 Torr With phosphorous pentoxide, hydrogen, potassium carbonate, acetic acid, palladium on activated charcoal in diethyl ether, ethanol, toluene, 2: Bischler-Napieralski reaction Tietze, Lutz F.; Rackelmann, Nils; Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences; vol. 59; nb. 4; (2004); p. 468 - 477 View in Reaxys O O

O N

O H 2N

Rx-ID: 13168558 View in Reaxys 61/177 Yield

Conditions & References Reaction Steps: 5 1: 61 percent / aq. K2CO3 / diethyl ether / 1.5 h / 0 °C 2: 59 percent / P4O10 / toluene / 1 h / Heating 3: 98 percent / H2; AcOH / Pd/C / ethanol / 1.17 h / 25 °C / 3075.25 Torr 4: 67 percent / Et3N / CH2Cl2 / 3 h / 25 °C 5: 70 percent / DIBAL / toluene / 1.33 h / -78 °C With phosphorous pentoxide, hydrogen, diisobutylaluminium hydride, potassium carbonate, acetic acid, triethylamine, palladium on activated charcoal in diethyl ether, ethanol, dichloromethane, toluene, 2: Bischler-Napieralski reaction Tietze, Lutz F.; Rackelmann, Nils; Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences; vol. 59; nb. 4; (2004); p. 468 - 477 View in Reaxys

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H 2N

racemate

Rx-ID: 13168559 View in Reaxys 62/177 Yield

Conditions & References Reaction Steps: 8 1: 61 percent / aq. K2CO3 / diethyl ether / 1.5 h / 0 °C 2: 59 percent / P4O10 / toluene / 1 h / Heating 3: 98 percent / H2; AcOH / Pd/C / ethanol / 1.17 h / 25 °C / 3075.25 Torr 4: 67 percent / Et3N / CH2Cl2 / 3 h / 25 °C 5: 70 percent / DIBAL / toluene / 1.33 h / -78 °C 6: 100 percent / ethylene diammonium diacetate / toluene / 5.5 h / 60 °C / ultrasonic bath 7: 12 percent / H2 / Pd/C / methanol / 4 h / 25 °C / 750.06 Torr 8: 44 percent / LiAlH4 / tetrahydrofuran / 4.5 h / 25 °C With lithium aluminium tetrahydride, phosphorous pentoxide, hydrogen, diisobutylaluminium hydride, potassium carbonate, acetic acid, ethylenediamine diacetic acid, triethylamine, palladium on activated charcoal in tetrahydrofuran, methanol, diethyl ether, ethanol, dichloromethane, toluene, 2: Bischler-Napieralski reaction / 6: domino Knoevenagel-hetero-Diels-Alder reaction Tietze, Lutz F.; Rackelmann, Nils; Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences; vol. 59; nb. 4; (2004); p. 468 - 477 View in Reaxys

O H

O N

O O

H 2N

racemate

Rx-ID: 13168560 View in Reaxys 63/177 Yield

Conditions & References Reaction Steps: 7 1: 61 percent / aq. K2CO3 / diethyl ether / 1.5 h / 0 °C 2: 59 percent / P4O10 / toluene / 1 h / Heating 3: 98 percent / H2; AcOH / Pd/C / ethanol / 1.17 h / 25 °C / 3075.25 Torr 4: 67 percent / Et3N / CH2Cl2 / 3 h / 25 °C 5: 70 percent / DIBAL / toluene / 1.33 h / -78 °C 6: 100 percent / ethylene diammonium diacetate / toluene / 5.5 h / 60 °C / ultrasonic bath 7: 12 percent / H2 / Pd/C / methanol / 4 h / 25 °C / 750.06 Torr With phosphorous pentoxide, hydrogen, diisobutylaluminium hydride, potassium carbonate, acetic acid, ethylenediamine diacetic acid, triethylamine, palladium on activated charcoal in methanol, diethyl ether, ethanol, dichloromethane, toluene, 2: Bischler-Napieralski reaction / 6: domino Knoevenagel-hetero-Diels-Alder reaction Tietze, Lutz F.; Rackelmann, Nils; Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences; vol. 59; nb. 4; (2004); p. 468 - 477 View in Reaxys

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O O

O N

H 2N O

Rx-ID: 13168561 View in Reaxys 64/177 Yield

Conditions & References Reaction Steps: 4 1: 61 percent / aq. K2CO3 / diethyl ether / 1.5 h / 0 °C 2: 59 percent / P4O10 / toluene / 1 h / Heating 3: 98 percent / H2; AcOH / Pd/C / ethanol / 1.17 h / 25 °C / 3075.25 Torr 4: 67 percent / Et3N / CH2Cl2 / 3 h / 25 °C With phosphorous pentoxide, hydrogen, potassium carbonate, acetic acid, triethylamine, palladium on activated charcoal in diethyl ether, ethanol, dichloromethane, toluene, 2: Bischler-Napieralski reaction Tietze, Lutz F.; Rackelmann, Nils; Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences; vol. 59; nb. 4; (2004); p. 468 - 477 View in Reaxys

N O

O O

H 2N

O O racemate

Rx-ID: 13168562 View in Reaxys 65/177 Yield

Conditions & References Reaction Steps: 6 1: 61 percent / aq. K2CO3 / diethyl ether / 1.5 h / 0 °C 2: 59 percent / P4O10 / toluene / 1 h / Heating 3: 98 percent / H2; AcOH / Pd/C / ethanol / 1.17 h / 25 °C / 3075.25 Torr 4: 67 percent / Et3N / CH2Cl2 / 3 h / 25 °C 5: 70 percent / DIBAL / toluene / 1.33 h / -78 °C 6: 100 percent / ethylene diammonium diacetate / toluene / 5.5 h / 60 °C / ultrasonic bath With phosphorous pentoxide, hydrogen, diisobutylaluminium hydride, potassium carbonate, acetic acid, ethylenediamine diacetic acid, triethylamine, palladium on activated charcoal in diethyl ether, ethanol, dichloromethane, toluene, 2: Bischler-Napieralski reaction / 6: domino Knoevenagel-hetero-Diels-Alder reaction Tietze, Lutz F.; Rackelmann, Nils; Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences; vol. 59; nb. 4; (2004); p. 468 - 477 View in Reaxys

F O

O I

H 2N O

Rx-ID: 15585979 View in Reaxys 66/177

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Yield

Conditions & References Reaction Steps: 2 1: 92 percent / 0 °C 2: 58 percent / ICl; NaI; 0.1 N NaOH / acetic acid / 20 °C With sodium hydroxide, iodine cloride, sodium iodide in acetic acid, 1: Acetylation / 2: Iodination Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p. 3074 - 3084 View in Reaxys F

O O

H 2N

Rx-ID: 15585984 View in Reaxys 67/177 Yield

Conditions & References Reaction Steps: 2 1: 92 percent / 0 °C 2: 18 percent / TiCl4 / CH2Cl2 / -30 - 20 °C With titanium tetrachloride in dichloromethane, 1: Acetylation / 2: Friedel-Crafts acylation Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p. 3074 - 3084 View in Reaxys

O O F

N H

H 2N

Rx-ID: 15585986 View in Reaxys 68/177 Yield

Conditions & References Reaction Steps: 2 1: 92 percent / 0 °C 2: 31 percent / TiCl4 / CH2Cl2 / -30 - 20 °C With titanium tetrachloride in dichloromethane, 1: Acetylation / 2: Friedel-Crafts acylation Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p. 3074 - 3084 View in Reaxys

F H 2N

O F

Rx-ID: 15585988 View in Reaxys 69/177 Yield

Conditions & References Reaction Steps: 3 1: 92 percent / 0 °C 2: 58 percent / ICl; NaI; 0.1 N NaOH / acetic acid / 20 °C 3: 65 percent / pyridine / 120 °C With pyridine, sodium hydroxide, iodine cloride, sodium iodide in acetic acid, 1: Acetylation / 2: Iodination / 3: Substitution Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p. 3074 - 3084

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View in Reaxys O O

O H 2N

Rx-ID: 20508198 View in Reaxys 70/177 Yield

Conditions & References Reaction Steps: 6 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C 3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating 4: 90 percent / hydrazine hydrate / ethanol / 2 h / Heating 5: 83 percent / acetic acid / 4 h / Ambient temperature 6: 79 percent / 2,6-pyridinedicarboxylic acid N-oxide, ammonium cerium(IV) nitrate / acetonitrile; H2O / 0.5 h With pyridine-2,6-dicarboxylate N-oxide, ammonium cerium(IV) nitrate, hydrazine hydrate, triethylamine, trichlorophosphate, palladium on activated charcoal in ethanol, water, acetic acid, toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys Cl O O

O O

H 2N

Rx-ID: 20508199 View in Reaxys 71/177 Yield

Conditions & References Reaction Steps: 6 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C 3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating 4: 90 percent / hydrazine hydrate / ethanol / 2 h / Heating 5: 72.5 percent / triethylamine / CH2Cl2 / 3 h / Ambient temperature 6: 43.5 percent / 2,6-pyridinedicarboxylic acid N-oxide, ammonium cerium(IV) nitrate / acetonitrile; H2O / 0.5 h With pyridine-2,6-dicarboxylate N-oxide, ammonium cerium(IV) nitrate, hydrazine hydrate, triethylamine, trichlorophosphate, palladium on activated charcoal in ethanol, dichloromethane, water, toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys O O

O O

H 2N O

Rx-ID: 20508200 View in Reaxys 72/177 Yield

Conditions & References Reaction Steps: 6 1: triethylamine / toluene / 1 h / 60 °C

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2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C 3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating 4: 90 percent / hydrazine hydrate / ethanol / 2 h / Heating 5: 0.5 h / 60 °C 6: 70 percent / 2,6-pyridinedicarboxylic acid N-oxide, ammonium cerium(IV) nitrate / acetonitrile; H2O / 0.5 h With pyridine-2,6-dicarboxylate N-oxide, ammonium cerium(IV) nitrate, hydrazine hydrate, triethylamine, trichlorophosphate, palladium on activated charcoal in ethanol, water, toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys O NH

O H 2N

Rx-ID: 20508201 View in Reaxys 73/177 Yield

Conditions & References Reaction Steps: 5 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C 3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating 4: 90 percent / hydrazine hydrate / ethanol / 2 h / Heating 5: 83 percent / acetic acid / 4 h / Ambient temperature With hydrazine hydrate, triethylamine, trichlorophosphate, palladium on activated charcoal in ethanol, acetic acid, toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys

NH NH

H 2N O

Rx-ID: 20508202 View in Reaxys 74/177 Yield

Conditions & References Reaction Steps: 6 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C 3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating 4: 90 percent / hydrazine hydrate / ethanol / 2 h / Heating 5: 72 percent / CH2Cl2 / 3 h / Ambient temperature 6: 10 percent / 2,6-pyridinedicarboxylic acid N-oxide, ammonium cerium(IV) nitrate / acetonitrile; H2O / 0.5 h With pyridine-2,6-dicarboxylate N-oxide, ammonium cerium(IV) nitrate, hydrazine hydrate, triethylamine, trichlorophosphate, palladium on activated charcoal in ethanol, dichloromethane, water, toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys

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O O O

O H 2N O

Rx-ID: 20508203 View in Reaxys 75/177 Yield

Conditions & References Reaction Steps: 5 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C 3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating 4: 90 percent / hydrazine hydrate / ethanol / 2 h / Heating 5: 0.5 h / 60 °C With hydrazine hydrate, triethylamine, trichlorophosphate, palladium on activated charcoal in ethanol, toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys Cl O O

O O

H 2N

Rx-ID: 20508204 View in Reaxys 76/177 Yield

Conditions & References Reaction Steps: 5 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C 3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating 4: 90 percent / hydrazine hydrate / ethanol / 2 h / Heating 5: 72.5 percent / triethylamine / CH2Cl2 / 3 h / Ambient temperature With hydrazine hydrate, triethylamine, trichlorophosphate, palladium on activated charcoal in ethanol, dichloromethane, toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys

O O

O N H 2N O

Rx-ID: 20508205 View in Reaxys 77/177 Yield

Conditions & References Reaction Steps: 5 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C

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3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating 4: 90 percent / hydrazine hydrate / ethanol / 2 h / Heating 5: 72 percent / CH2Cl2 / 3 h / Ambient temperature With hydrazine hydrate, triethylamine, trichlorophosphate, palladium on activated charcoal in ethanol, dichloromethane, toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys

O NH

O O

N H 2N O

Rx-ID: 20508206 View in Reaxys 78/177 Yield

Conditions & References Reaction Steps: 5 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C 3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating 4: 90 percent / hydrazine hydrate / ethanol / 2 h / Heating 5: 88 percent / CH2Cl2 / 3 h / Ambient temperature With hydrazine hydrate, triethylamine, trichlorophosphate, palladium on activated charcoal in ethanol, dichloromethane, toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys

N O

H 2N

Rx-ID: 20508208 View in Reaxys 79/177 Yield

Conditions & References Reaction Steps: 6 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C 3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating 4: 90 percent / hydrazine hydrate / ethanol / 2 h / Heating 5: 72.5 percent / triethylamine / CH2Cl2 / 3 h / Ambient temperature 6: 47 percent / ethanol / 3 h / Heating With hydrazine hydrate, triethylamine, trichlorophosphate, palladium on activated charcoal in ethanol, dichloromethane, toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys

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O N

O H 2N O

Rx-ID: 20508209 View in Reaxys 80/177 Yield

Conditions & References Reaction Steps: 3 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C 3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating With triethylamine, trichlorophosphate, palladium on activated charcoal in toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys

O O

S NH

H 2N O

Rx-ID: 20508210 View in Reaxys 81/177 Yield

Conditions & References Reaction Steps: 5 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C 3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating 4: 90 percent / hydrazine hydrate / ethanol / 2 h / Heating 5: 56 percent / pyridine / 4 h / Ambient temperature With pyridine, hydrazine hydrate, triethylamine, trichlorophosphate, palladium on activated charcoal in ethanol, toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys

NH 2

N O H 2N

Rx-ID: 20508211 View in Reaxys 82/177 Yield

Conditions & References Reaction Steps: 4 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C 3: 80 percent / 10percent Pd/C / decahydronaphthalene / 6 h / Heating 4: 90 percent / hydrazine hydrate / ethanol / 2 h / Heating With hydrazine hydrate, triethylamine, trichlorophosphate, palladium on activated charcoal in ethanol, toluene, acetonitrile, decalin Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660

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View in Reaxys

HN OH

H 2N

Rx-ID: 21990502 View in Reaxys 83/177 Yield

Conditions & References Reaction Steps: 2 1: benzaldehyde / beim Erwaermen des Kondensationsprodukts mit Methyljodid in Benzol und Erwaermen des Reaktionsprodukts mit wasserhaltigem Aethanol With benzaldehyde Buck; Journal of the American Chemical Society; vol. 54; (1932); p. 3661,3662 View in Reaxys

H N

Cl O

Br O

H 2N

Rx-ID: 22286156 View in Reaxys 84/177 Yield

Conditions & References Reaction Steps: 2 2: acetic acid; bromine With bromine, acetic acid Phillips; Journal of the American Chemical Society; vol. 75; (1953); p. 3621 View in Reaxys

O N

H 2N

Rx-ID: 106878 View in Reaxys 85/177 Yield

Conditions & References With methanol Phillips; Journal of the American Chemical Society; vol. 75; (1953); p. 3521 View in Reaxys

Cl O O

Cl Cl

H N

Cl Cl

O O

H 2N

Rx-ID: 145364 View in Reaxys 86/177 Yield

Conditions & References With methanol Phillips; Journal of the American Chemical Society; vol. 75; (1953); p. 3621 View in Reaxys

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O –N

K+

H N

NH 2

H 2N

Rx-ID: 145365 View in Reaxys 87/177 Yield

Conditions & References With sulfuric acid Buck; Journal of the American Chemical Society; vol. 56; (1934); p. 1607 View in Reaxys

H N

O HO

H 2N

Rx-ID: 1629544 View in Reaxys 88/177 Yield

Conditions & References

88.2 %

in toluene, Petroleum ether, reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys

O Cl

O NH

H 2N

Rx-ID: 1972005 View in Reaxys 89/177 Yield

Conditions & References With triethylamine in toluene, Time= 1h, T= 60 °C , Yield given Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys

HN O H 2N

S S

Rx-ID: 4419920 View in Reaxys 90/177 Yield

Conditions & References in acetonitrile, Time= 1h, T= 100 °C Bell; Cantrell; Hogberg; Jaskunas; Johansson; Jordan; Kinnick; Lind; Morin Jr.; Noreen; Oberg; Palkowitz; Parrish; Pranc; Sahlberg; Ternansky; Vasileff; Vrang; West; et al.; Journal of Medicinal Chemistry; vol. 38; nb. 25; (1995); p. 4929 - 4936 View in Reaxys

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NH 2 HCl

NH 2 2H 2H

O 2H

Rx-ID: 11289585 View in Reaxys 91/177 Yield

Conditions & References

29 %

With sulfuryl dichloride, acetic acid, Time= 3h, T= 20 °C Xu, Ya-Zhu; Chen, Chinpiao; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 49; nb. 13; (2006); p. 1187 - 1200 View in Reaxys

HO O

O HO

H N O

H 2N

Rx-ID: 22883469 View in Reaxys 92/177 Yield

Conditions & References 54 : EXAMPLE 54; (2S)-3-(4-{1-[2-(2,5-dimethoxy-phenyl)-ethylcarbamoyl]-1-methyl-ethoxy}-phenyl)-2ethoxy-propionic acid The title compound was prepared from [(2S)-3- [4- (1-CARBOXY-1-METHYL-ETHOXY)-] phenyl] -2-ethoxy-propionic acid ethyl ester (EXAMPLE 49, step 2) and 2- (2, 5- [DIMETHOXY-PHENYL)-ETHYLAMINE] via the same procedure used for the preparation of (2S, 1R)-2-ethoxy-3-(4-{1-[2-(4-phenoxy-phenyl)-ethylcarbamoyl]-ethoxy}-phenyl)- propionic acid (Example 1, step 3) to produce a colorless oil. MS (ES) for [C25H33NO7] [M-H]-: 458. Patent; ELI LILLY AND COMPANY; WO2004/789; (2003); (A1) English View in Reaxys

O HO

H N O

H 2N

Rx-ID: 22883519 View in Reaxys 93/177 Yield

Conditions & References 47 : EXAMPLE 47; (2S)-3-(4-{1-[2-(2,5-dimethoxy-phenyl)-ethylcarbamoyl]-1-methyl-ethoxy}-phenyl)-2-methoxy-propionic acid The title compound was prepared from (2S)-3-[4-(1-carboxy-1-methyl-ethoxy)- phenyl] -2-methoxy-propionic acid ethyl ester (PREPARATION 5, step 2) and 2- (2, 5- dimethoxy-phenyl) -ethylamine via the same procedure used for the preparation of (2S, [1 R)-2-ETHOXY-3- (4- {1- [2- (4-PHENOXY-PHENYL)-ETHYLCARBAMOYL]-ETHOXY}PHENYL)-] propionic acid (Example 1, step 3) to produce a colorless oil. MS (ES) for [C24H3LNO7] [[M-H]- :] 445. Patent; ELI LILLY AND COMPANY; WO2004/789; (2003); (A1) English View in Reaxys

O O

O H 2N

N H

Rx-ID: 27978914 View in Reaxys 94/177

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Yield

Conditions & References in isopropyl alcohol, Time= 16h, T= 90 °C Goode, David R.; Totten, Ryan K.; Heeres, James T.; Hergenrother, Paul J.; Journal of Medicinal Chemistry; vol. 51; nb. 8; (2008); p. 2346 - 2349 View in Reaxys

O O

H 2N

N H

Rx-ID: 27978952 View in Reaxys 95/177 Yield

HCl O

H 2N O

Rx-ID: 31269669 View in Reaxys 96/177 Yield

Conditions & References

51 %

Stage 1: in ethanol, Time= 0.166667h, Reflux, Mannich reaction Stage 2: With hydrogenchloride in diethyl ether, acetone Afon'kin; Kostrikin; Shumeiko; Popov; Russian Journal of Organic Chemistry; vol. 47; nb. 5; (2011); p. 731 - 745 View in Reaxys

H N

O O

H 2N

Rx-ID: 1635546 View in Reaxys 97/177 Yield

Conditions & References

83 %

HO O

H N

O O

H 2N

Rx-ID: 1796306 View in Reaxys 98/177 Yield 84.5 %

Conditions & References in toluene, Petroleum ether, reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h

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Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys O

O O

H N

H 2N

Rx-ID: 5050295 View in Reaxys 99/177 Yield

Conditions & References

88 %

Acylation Boger, Dale L.; Chai, Wenying; Ozer, Rachel S.; Andersson, Carl-Magnus; Bioorganic and Medicinal Chemistry Letters; vol. 7; nb. 4; (1997); p. 463 - 468 View in Reaxys in N,N-dimethyl-formamide, T= 25 °C , Acylation Boger, Dale L.; Chai, Wenying; Tetrahedron; vol. 54; nb. 16; (1998); p. 3955 - 3970 View in Reaxys

H N

O O

H 2N

Rx-ID: 1796307 View in Reaxys 100/177 Yield

Conditions & References

71.2 %

H N

O O

H 2N

Rx-ID: 1796309 View in Reaxys 101/177 Yield 71 %

Conditions & References in toluene, Petroleum ether, reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys

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2H 2H

O N

NH 2 2H 2H

2H 2H

O O 2H

Rx-ID: 11289586 View in Reaxys 102/177 Yield

Conditions & References

71 %

T= 130 °C Xu, Ya-Zhu; Chen, Chinpiao; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 49; nb. 13; (2006); p. 1187 - 1200 View in Reaxys

H N O

H 2N

Rx-ID: 20380572 View in Reaxys 103/177 Yield

Conditions & References Reaction Steps: 2 1: benzene / Heating 2: NaBH4 / ethanol / 0.5 h / Ambient temperature With sodium tetrahydroborate in ethanol, benzene Kubo, Akinori; Saito, Naoki; Kawakami, Nanko; Matsuyama, Yasuo; Miwa, Teruyo; Synthesis; nb. 9; (1987); p. 824 - 827 View in Reaxys

O O

N O

H 2N

Rx-ID: 20380573 View in Reaxys 104/177 Yield

Conditions & References Reaction Steps: 4 1: benzene / Heating 2: NaBH4 / ethanol / 0.5 h / Ambient temperature 3: K2CO3 / Ambient temperature 4: trifluoroacetic acid / 1 h / Ambient temperature With sodium tetrahydroborate, potassium carbonate, trifluoroacetic acid in ethanol, benzene Kubo, Akinori; Saito, Naoki; Kawakami, Nanko; Matsuyama, Yasuo; Miwa, Teruyo; Synthesis; nb. 9; (1987); p. 824 - 827 View in Reaxys

O O

N O

H 2N

Rx-ID: 20380574 View in Reaxys 105/177 Yield

Conditions & References Reaction Steps: 3

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1: benzene / Heating 2: NaBH4 / ethanol / 0.5 h / Ambient temperature 3: K2CO3 / Ambient temperature With sodium tetrahydroborate, potassium carbonate in ethanol, benzene Kubo, Akinori; Saito, Naoki; Kawakami, Nanko; Matsuyama, Yasuo; Miwa, Teruyo; Synthesis; nb. 9; (1987); p. 824 - 827 View in Reaxys

H 2N

Rx-ID: 20380575 View in Reaxys 106/177 Yield

Conditions & References Reaction Steps: 3 1: benzene / Heating 2: NaBH4 / ethanol / 0.5 h / Ambient temperature 3: 1.) K2CO3, 2.) CF3CO2H / 1.) butanol, r.t., 30 min. 2.) r.t., 60 min. With sodium tetrahydroborate, potassium carbonate, trifluoroacetic acid in ethanol, benzene Kubo, Akinori; Saito, Naoki; Kawakami, Nanko; Matsuyama, Yasuo; Miwa, Teruyo; Synthesis; nb. 9; (1987); p. 824 - 827 View in Reaxys

alkaline permanganate

H 2N

Rx-ID: 20403277 View in Reaxys 107/177 Yield

Conditions & References Reaction Steps: 2 1: ammonium acetate / 3 h / Heating 2: LiAlH4 / tetrahydrofuran / 4 h / Ambient temperature With ammonium acetate, lithium aluminium tetrahydride in tetrahydrofuran Kubo, Akinori; Saito, Naoki; Kawakami, Nanko; Matsuyama, Yasuo; Miwa, Teruyo; Synthesis; nb. 9; (1987); p. 824 - 827 View in Reaxys

H N O

S N H

NH 2

H 2N

Rx-ID: 29442537 View in Reaxys 108/177 Yield 20 %

Conditions & References in bromobenzene, T= 20 °C , Reflux Marugan, Juan J.; Zheng, Wei; Motabar, Omid; Southall, Noel; Goldin, Ehud; Sidransky, Ellen; Aungst, Ronald A.; Liu, Ke; Sadhukhan, Subir Kumar; Austin, Christopher P.; European Journal of Medicinal Chemistry; vol. 45; nb. 5; (2010); p. 1880 - 1897 View in Reaxys

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O O

O HO

H 2N

Rx-ID: 31927091 View in Reaxys 109/177 Yield

Conditions & References Reaction Steps: 2 1: toluene / Reflux 2: trifluorormethanesulfonic acid / dichloromethane / 12 h / 0 - 20 °C / Inert atmosphere With trifluorormethanesulfonic acid in dichloromethane, toluene Selvakumar, Jayaraman; Ramanathan, Chinnasamy Ramaraj; Organic and Biomolecular Chemistry; vol. 9; nb. 22; (2011); p. 7643 - 7646 View in Reaxys

O NH

O O

H 2N

O O

S O

Rx-ID: 39269981 View in Reaxys 110/177 Yield

Conditions & References Reaction Steps: 4 1: sodium hydroxide / water; acetic acid; benzene 2: triethylamine / dichloromethane; hexane; ethyl acetate; chloroform 3: hexane; tetrahydrofuran; ethyl acetate; methanol 4: hexane; water; ethyl acetate; pyridine With sodium hydroxide, triethylamine in tetrahydrofuran, pyridine, methanol, hexane, dichloromethane, chloroform, water, acetic acid, ethyl acetate, benzene Patent; Benchikh, Elouard; Fitzgerald, Peter; McConnell, Ivan; Lowry, Philip; US2015/38366; (2015); (A1) English View in Reaxys Reaction Steps: 4 1: sodium hydroxide / water; acetic acid; benzene 2: triethylamine / dichloromethane; hexane; ethyl acetate; chloroform 3: hexane; tetrahydrofuran; ethyl acetate; methanol 4: hexane; water; ethyl acetate; pyridine With sodium hydroxide, triethylamine in tetrahydrofuran, pyridine, methanol, hexane, dichloromethane, chloroform, water, acetic acid, ethyl acetate, benzene Patent; Randox Laboratories Ltd.; Benchikh, Elouard; Fitzgerald, Peter; McConnell, Ivan; Lowry, Philip; EP2835648; (2015); (A1) English View in Reaxys

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H N

H 2N

Rx-ID: 555680 View in Reaxys 111/177 Yield

Conditions & References Sugasawa; Shigehara; Chemische Berichte; vol. 74; (1941); p. 459,462 View in Reaxys With pyridine, Time= 1h, T= 60 °C , Yield given Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys

O H 2N

Rx-ID: 1796308 View in Reaxys 112/177 Yield

Conditions & References

62.3 %

H N

H 2N

Rx-ID: 9303828 View in Reaxys 113/177 Yield

Conditions & References in N,N-dimethyl-formamide, T= 110 °C Venkatachalam; Qazi; Samuel; Uckun; Bioorganic and Medicinal Chemistry; vol. 11; nb. 6; (2003); p. 1095 - 1105 View in Reaxys

H N

N F

F F

H 2N

H N

Rx-ID: 9303829 View in Reaxys 114/177 Yield

Conditions & References in N,N-dimethyl-formamide, T= 110 °C Venkatachalam; Qazi; Samuel; Uckun; Bioorganic and Medicinal Chemistry; vol. 11; nb. 6; (2003); p. 1095 - 1105 View in Reaxys

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O O

O O H 2N

O O

Rx-ID: 9717869 View in Reaxys 115/177 Yield

Conditions & References With 4-(N,N-dimethlyamino)pyridine, 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride in N,N-dimethyl-formamide Tao, Houchao; Hwang, Inkyu; Boger, Dale L.; Bioorganic and Medicinal Chemistry Letters; vol. 14; nb. 24; (2004); p. 5979 - 5981 View in Reaxys

O N

H 2N

Rx-ID: 39269979 View in Reaxys 116/177 Yield

Conditions & References Reaction Steps: 2 1: sodium hydroxide / water; acetic acid; benzene 2: triethylamine / dichloromethane; hexane; ethyl acetate; chloroform With sodium hydroxide, triethylamine in hexane, dichloromethane, chloroform, water, acetic acid, ethyl acetate, benzene Patent; Benchikh, Elouard; Fitzgerald, Peter; McConnell, Ivan; Lowry, Philip; US2015/38366; (2015); (A1) English View in Reaxys Patent; Randox Laboratories Ltd.; Benchikh, Elouard; Fitzgerald, Peter; McConnell, Ivan; Lowry, Philip; EP2835648; (2015); (A1) English View in Reaxys

O NH 2 O

H 2N

Rx-ID: 39269980 View in Reaxys 117/177 Yield

Conditions & References Reaction Steps: 3 1: sodium hydroxide / water; acetic acid; benzene 2: triethylamine / dichloromethane; hexane; ethyl acetate; chloroform 3: hexane; tetrahydrofuran; ethyl acetate; methanol With sodium hydroxide, triethylamine in tetrahydrofuran, methanol, hexane, dichloromethane, chloroform, water, acetic acid, ethyl acetate, benzene

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Patent; Benchikh, Elouard; Fitzgerald, Peter; McConnell, Ivan; Lowry, Philip; US2015/38366; (2015); (A1) English View in Reaxys Patent; Randox Laboratories Ltd.; Benchikh, Elouard; Fitzgerald, Peter; McConnell, Ivan; Lowry, Philip; EP2835648; (2015); (A1) English View in Reaxys

O NH

O O

HN H 2N

O O

HO O

Rx-ID: 39269982 View in Reaxys 118/177 Yield

Conditions & References Reaction Steps: 4 1: sodium hydroxide / water; acetic acid; benzene 2: triethylamine / dichloromethane; hexane; ethyl acetate; chloroform 3: hexane; tetrahydrofuran; ethyl acetate; methanol 4: triethylamine; hydrogenchloride / chloroform; methanol; pyridine With hydrogenchloride, sodium hydroxide, triethylamine in tetrahydrofuran, pyridine, methanol, hexane, dichloromethane, chloroform, water, acetic acid, ethyl acetate, benzene Patent; Benchikh, Elouard; Fitzgerald, Peter; McConnell, Ivan; Lowry, Philip; US2015/38366; (2015); (A1) English View in Reaxys Patent; Randox Laboratories Ltd.; Benchikh, Elouard; Fitzgerald, Peter; McConnell, Ivan; Lowry, Philip; EP2835648; (2015); (A1) English View in Reaxys

O O

O N

H 2N

O N O

Rx-ID: 3455201 View in Reaxys 119/177 Yield

Conditions & References

52 %

in methanol Heberer, H.; Kersting, H.; Matschiner, H.; Journal fuer Praktische Chemie (Leipzig); vol. 327; nb. 3; (1985); p. 487 - 504 View in Reaxys

O Cl

O N O

H 2N

Rx-ID: 11289583 View in Reaxys 120/177 Yield

Conditions & References With lithium aluminium tetrahydride in tetrahydrofuran, Time= 24h, Heating

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Xu, Ya-Zhu; Chen, Chinpiao; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 49; nb. 13; (2006); p. 1187 - 1200 View in Reaxys

Cl O

H 2N O

H 2N

Rx-ID: 11289587 View in Reaxys 121/177 Yield

Conditions & References With sulfuryl dichloride, acetic acid, Time= 3h, T= 20 °C Xu, Ya-Zhu; Chen, Chinpiao; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 49; nb. 13; (2006); p. 1187 - 1200 View in Reaxys

O O

H 2N

Rx-ID: 13168557 View in Reaxys 122/177 Yield

Conditions & References Reaction Steps: 2 1: 61 percent / aq. K2CO3 / diethyl ether / 1.5 h / 0 °C 2: 59 percent / P4O10 / toluene / 1 h / Heating With phosphorous pentoxide, potassium carbonate in diethyl ether, toluene, 2: Bischler-Napieralski reaction Tietze, Lutz F.; Rackelmann, Nils; Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences; vol. 59; nb. 4; (2004); p. 468 - 477 View in Reaxys

H N

NH 2 O

H 2N

Rx-ID: 19397525 View in Reaxys 123/177 Yield

Conditions & References Reaction Steps: 2 1: 80 percent / acetic acid, nitric acid / 1 h / 0 °C 2: 48 percent / concd HCl, Sn / 1 h / Heating With hydrogenchloride, tin, nitric acid, acetic acid Cheng; Castagnoli Jr.; Journal of Medicinal Chemistry; vol. 27; nb. 4; (1984); p. 513 - 520 View in Reaxys

NH 2 N

O H 2N

O OH

Rx-ID: 19397526 View in Reaxys 124/177

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Yield

Conditions & References Reaction Steps: 2 1: 80 percent / acetic acid, nitric acid / 1 h / 0 °C 2: 48percent aq. HBr / 6 h / Heating With hydrogen bromide, nitric acid, acetic acid Cheng; Castagnoli Jr.; Journal of Medicinal Chemistry; vol. 27; nb. 4; (1984); p. 513 - 520 View in Reaxys

O O

N O

H 2N

Rx-ID: 19397527 View in Reaxys 125/177 Yield

Conditions & References Reaction Steps: 2 1: benzene / Heating 2: 26 percent / C7H7SO3H / benzene / Heating With C7H7SO3H in benzene Freeman, Jeremiah P.; Fettes-Fields, Mary Kay; Heterocycles; vol. 23; nb. 5; (1985); p. 1073 - 1076 View in Reaxys

NH 2 O

H 2N OH

H 2N

Rx-ID: 19397528 View in Reaxys 126/177 Yield

Conditions & References Reaction Steps: 3 1: 80 percent / acetic acid, nitric acid / 1 h / 0 °C 2: 48 percent / concd HCl, Sn / 1 h / Heating 3: 48percent aq. HBr / 6 h / Heating With hydrogenchloride, tin, hydrogen bromide, nitric acid, acetic acid Cheng; Castagnoli Jr.; Journal of Medicinal Chemistry; vol. 27; nb. 4; (1984); p. 513 - 520 View in Reaxys

N O N

O H 2N O

Rx-ID: 20508207 View in Reaxys 127/177 Yield

Conditions & References Reaction Steps: 2 1: triethylamine / toluene / 1 h / 60 °C 2: 66 percent / POCl3 / acetonitrile / 1 h, reflux, then 80 deg C With triethylamine, trichlorophosphate in toluene, acetonitrile Croisy-Delcey, Martine; Huel, Christianne; Bisagni, Emile; Journal of Heterocyclic Chemistry; vol. 25; nb. 2; (1988); p. 655 - 660 View in Reaxys

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O O

H 2N

Rx-ID: 20708679 View in Reaxys 128/177 Yield

Conditions & References Reaction Steps: 2 1: 62.3 percent / toluene; light petroleum / reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h 2: 1.) phosphoryl trichloride, 2.) 60percent perchloric acid / 1.) CHCl3, reflux, 5-12 h, water, 60 deg C, 30 min, 2.) 2 deg C, several h With perchloric acid, trichlorophosphate in toluene, Petroleum ether Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys

O O

H 2N O

Rx-ID: 20708680 View in Reaxys 129/177 Yield

Conditions & References Reaction Steps: 2 1: 71 percent / toluene; light petroleum / reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h 2: 1.) phosphoryl trichloride, 2.) 60percent perchloric acid / 1.) CHCl3, reflux, 5-12 h, water, 60 deg C, 30 min, 2.) 2 deg C, several h With perchloric acid, trichlorophosphate in toluene, Petroleum ether Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys OH

O Br H

NH O

H 2N HO

Rx-ID: 20708681 View in Reaxys 130/177 Yield

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O O

Br H

H 2N

Rx-ID: 20708682 View in Reaxys 131/177 Yield

Conditions & References Reaction Steps: 4 1: 62.3 percent / toluene; light petroleum / reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h 2: 1.) phosphoryl trichloride, 2.) 60percent perchloric acid / 1.) CHCl3, reflux, 5-12 h, water, 60 deg C, 30 min, 2.) 2 deg C, several h 3: 1.) sodium borohydride, 2.) HCl / 1.) ethanol, 60 min 4: 97 percent / 48percent HBr / reflux, 4 h, 2 deg C, 2 h With hydrogenchloride, sodium tetrahydroborate, perchloric acid, hydrogen bromide, trichlorophosphate in toluene, Petroleum ether Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys OH O O

H 2N

Rx-ID: 20708683 View in Reaxys 132/177 Yield

Conditions & References Reaction Steps: 4 1: 71 percent / toluene; light petroleum / reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h 2: 1.) phosphoryl trichloride, 2.) 60percent perchloric acid / 1.) CHCl3, reflux, 5-12 h, water, 60 deg C, 30 min, 2.) 2 deg C, several h 3: 1.) sodium borohydride, 2.) HCl / 1.) ethanol, 60 min 4: 1.) boron tribromide, 2.) 48percent HBr / 1.) CH2Cl2, -60 deg C, r.t., overnight, 2.) 5 min With hydrogenchloride, sodium tetrahydroborate, perchloric acid, hydrogen bromide, boron tribromide, trichlorophosphate in toluene, Petroleum ether Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys

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O O

Br H

H 2N

Rx-ID: 20708684 View in Reaxys 133/177 Yield

Conditions & References Reaction Steps: 5 1: 62.3 percent / toluene; light petroleum / reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h 2: 1.) phosphoryl trichloride, 2.) 60percent perchloric acid / 1.) CHCl3, reflux, 5-12 h, water, 60 deg C, 30 min, 2.) 2 deg C, several h 3: 92.3 percent / butan-2-one; benzene / 50 °C / 5-7 h 4: 1.) sodium borohydride, 2.) HCl / 1.) ethanol, 60 min 5: 77 percent / 48percent HBr / reflux, 4 h, 2 deg C, 2 h With hydrogenchloride, sodium tetrahydroborate, perchloric acid, hydrogen bromide, trichlorophosphate in toluene, butanone, Petroleum ether, benzene Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys

O O

H 2N

Rx-ID: 20708685 View in Reaxys 134/177 Yield

Conditions & References Reaction Steps: 3 1: 62.3 percent / toluene; light petroleum / reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h 2: 1.) phosphoryl trichloride, 2.) 60percent perchloric acid / 1.) CHCl3, reflux, 5-12 h, water, 60 deg C, 30 min, 2.) 2 deg C, several h 3: 1.) sodium borohydride, 2.) HCl / 1.) ethanol, 60 min With hydrogenchloride, sodium tetrahydroborate, perchloric acid, trichlorophosphate in toluene, Petroleum ether Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys

O O

H 2N

Rx-ID: 20708686 View in Reaxys 135/177

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Yield

Conditions & References Reaction Steps: 4 1: 62.3 percent / toluene; light petroleum / reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h 2: 1.) phosphoryl trichloride, 2.) 60percent perchloric acid / 1.) CHCl3, reflux, 5-12 h, water, 60 deg C, 30 min, 2.) 2 deg C, several h 3: 92.3 percent / butan-2-one; benzene / 50 °C / 5-7 h 4: 1.) sodium borohydride, 2.) HCl / 1.) ethanol, 60 min With hydrogenchloride, sodium tetrahydroborate, perchloric acid, trichlorophosphate in toluene, butanone, Petroleum ether, benzene Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys

O O

H 2N O

Rx-ID: 20708687 View in Reaxys 136/177 Yield

Conditions & References Reaction Steps: 3 1: 71 percent / toluene; light petroleum / reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h 2: 1.) phosphoryl trichloride, 2.) 60percent perchloric acid / 1.) CHCl3, reflux, 5-12 h, water, 60 deg C, 30 min, 2.) 2 deg C, several h 3: 1.) sodium borohydride, 2.) HCl / 1.) ethanol, 60 min With hydrogenchloride, sodium tetrahydroborate, perchloric acid, trichlorophosphate in toluene, Petroleum ether Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys

I–

O N+

H 2N

Rx-ID: 20708688 View in Reaxys 137/177 Yield

Conditions & References Reaction Steps: 6 1: 62.3 percent / toluene; light petroleum / reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h 2: 1.) phosphoryl trichloride, 2.) 60percent perchloric acid / 1.) CHCl3, reflux, 5-12 h, water, 60 deg C, 30 min, 2.) 2 deg C, several h 3: 1.) sodium borohydride, 2.) HCl / 1.) ethanol, 60 min 4: 97 percent / 48percent HBr / reflux, 4 h, 2 deg C, 2 h 5: sodium carbonate / H2O / 2 h 6: 34 percent / sodium hydride / tetrahydrofuran / Ambient temperature With hydrogenchloride, sodium tetrahydroborate, perchloric acid, hydrogen bromide, sodium hydride, sodium carbonate, trichlorophosphate in tetrahydrofuran, water, toluene, Petroleum ether Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462

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View in Reaxys

O I–

N+

H 2N

Rx-ID: 20708689 View in Reaxys 138/177 Yield

Conditions & References Reaction Steps: 3 1: 62.3 percent / toluene; light petroleum / reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h 2: 1.) phosphoryl trichloride, 2.) 60percent perchloric acid / 1.) CHCl3, reflux, 5-12 h, water, 60 deg C, 30 min, 2.) 2 deg C, several h 3: 92.3 percent / butan-2-one; benzene / 50 °C / 5-7 h With perchloric acid, trichlorophosphate in toluene, butanone, Petroleum ether, benzene Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys

O O

H 2N

Rx-ID: 20708690 View in Reaxys 139/177 Yield

Conditions & References Reaction Steps: 5 1: 62.3 percent / toluene; light petroleum / reflux, 12-20 h, 55-60 deg C -> 2 deg C, several h 2: 1.) phosphoryl trichloride, 2.) 60percent perchloric acid / 1.) CHCl3, reflux, 5-12 h, water, 60 deg C, 30 min, 2.) 2 deg C, several h 3: 1.) sodium borohydride, 2.) HCl / 1.) ethanol, 60 min 4: 97 percent / 48percent HBr / reflux, 4 h, 2 deg C, 2 h 5: sodium carbonate / H2O / 2 h With hydrogenchloride, sodium tetrahydroborate, perchloric acid, hydrogen bromide, sodium carbonate, trichlorophosphate in water, toluene, Petroleum ether Copp, Frederick C.; Franzmann, Karl W.; Grundy, Julian; Whalley, W. Basil; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1985); p. 2455 - 2462 View in Reaxys

O N H

H 2N

Rx-ID: 32653879 View in Reaxys 140/177 Yield

Conditions & References Reaction Steps: 2

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1.1: triethylamine / dichloromethane / 6 h / 20 °C / Cooling with ice 2.1: potassium tert-butylate / N,N-dimethyl-formamide / 0.5 h / Cooling with ice 2.2: Cooling with ice With potassium tert-butylate, triethylamine in dichloromethane, N,N-dimethyl-formamide Wang, Jin-Liang; Zhang, Jun; Zhou, Zhi-Ming; Li, Zhi-Huai; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, XiaoFeng; Fei, Fan; Liu, Ting; Liang, Ai-Hua; European Journal of Medicinal Chemistry; vol. 49; (2012); p. 183 - 190 View in Reaxys

O N

N H

H 2N

Rx-ID: 32653880 View in Reaxys 141/177 Yield

Conditions & References Reaction Steps: 3 1.1: triethylamine / dichloromethane / 6 h / 20 °C / Cooling with ice 2.1: potassium tert-butylate / N,N-dimethyl-formamide / 0.5 h / Cooling with ice 2.2: Cooling with ice 3.1: methanol; sodium hydroxide / 3 h / Reflux 3.2: pH 6 With methanol, potassium tert-butylate, triethylamine, sodium hydroxide in dichloromethane, N,N-dimethyl-formamide Wang, Jin-Liang; Zhang, Jun; Zhou, Zhi-Ming; Li, Zhi-Huai; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, XiaoFeng; Fei, Fan; Liu, Ting; Liang, Ai-Hua; European Journal of Medicinal Chemistry; vol. 49; (2012); p. 183 - 190 View in Reaxys

O O

N H

N N

H 2N

Rx-ID: 33642668 View in Reaxys 142/177 Yield

Conditions & References Reaction Steps: 2 1.1: triethylamine / chloroform / 8 h / 0 - 25 °C 2.1: potassium tert-butylate / N,N-dimethyl-formamide / 0.5 h / 0 °C 2.2: 12 h / 0 - 25 °C With potassium tert-butylate, triethylamine in chloroform, N,N-dimethyl-formamide Zhang, Jun; Wang, Jin-Liang; Zhou, Zhi-Ming; Li, Zhi-Huai; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, XiaoFeng; Fei, Fan; Liu, Ting; Liang, Ai-Hua; Bioorganic and Medicinal Chemistry; vol. 20; nb. 14; (2012); p. 4208 4216 View in Reaxys

O N H

H 2N

N N

NH N

Rx-ID: 33642669 View in Reaxys 143/177

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Yield

Conditions & References Reaction Steps: 3 1.1: triethylamine / chloroform / 8 h / 0 - 25 °C 2.1: potassium tert-butylate / N,N-dimethyl-formamide / 0.5 h / 0 °C 2.2: 12 h / 0 - 25 °C 3.1: hydrogenchloride / tetrahydrofuran; methanol; water / 12 h / 25 °C 3.2: pH 12 3.3: pH 6 - 7 With hydrogenchloride, potassium tert-butylate, triethylamine in tetrahydrofuran, methanol, chloroform, water, N,Ndimethyl-formamide Zhang, Jun; Wang, Jin-Liang; Zhou, Zhi-Ming; Li, Zhi-Huai; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, XiaoFeng; Fei, Fan; Liu, Ting; Liang, Ai-Hua; Bioorganic and Medicinal Chemistry; vol. 20; nb. 14; (2012); p. 4208 4216 View in Reaxys

O N

N N

H 2N

Rx-ID: 34501819 View in Reaxys 144/177 Yield

Conditions & References Reaction Steps: 3 1.1: toluene / 0.17 h / 80 °C / |Sealed tube; |Microwave irradiation 1.2: 0.17 h / 80 °C / |Sealed tube; |Microwave irradiation 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.5 h / 0 °C 3.1: trifluoroacetic anhydride / ethanol / 1.5 h / 75 °C / |Microwave irradiation With 3-chloro-benzenecarboperoxoic acid, trifluoroacetic anhydride in ethanol, dichloromethane, toluene Islas-Jacome, Alejandro; Cardenas-Galindo, Luis E.; Jerezano, Alberto V.; Tamariz, Joaquin; Gonzalez-Zamora, Eduardo; Gamez-Montano, Rocio; Synlett; vol. 23; nb. 20; (2012); p. 2951 - 2956 View in Reaxys

O O

O N

N O

O S

H 2N

Rx-ID: 34501820 View in Reaxys 145/177 Yield

Conditions & References Reaction Steps: 2 1.1: toluene / 0.17 h / 80 °C / |Sealed tube; |Microwave irradiation 1.2: 0.17 h / 80 °C / |Sealed tube; |Microwave irradiation 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.5 h / 0 °C With 3-chloro-benzenecarboperoxoic acid in dichloromethane, toluene Islas-Jacome, Alejandro; Cardenas-Galindo, Luis E.; Jerezano, Alberto V.; Tamariz, Joaquin; Gonzalez-Zamora, Eduardo; Gamez-Montano, Rocio; Synlett; vol. 23; nb. 20; (2012); p. 2951 - 2956 View in Reaxys

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H 13C

H 13C 13CH O

13C

13CH

H 13C 13CH

13C

C H

13C

HCl

H 2N

Rx-ID: 38014760 View in Reaxys 146/177 Yield

Conditions & References Reaction Steps: 6 1.1: N-bromosuccinmide / chloroform; N,N-dimethyl-formamide / 70 °C 2.1: copper(l) iodide; ethyl acetate / N,N-dimethyl-formamide; methanol / 48 h / 80 °C / |Sealed tube; |Inert atmosphere 3.1: titanium tetrachloride / dichloromethane / 17 h / -5 - 4 °C / |Inert atmosphere 4.1: ammonium acetate / 2 h / 70 °C 5.1: sodium tetrahydroborate; ethanol / ethyl acetate / 1 h / 22 °C 6.1: hydrogen; palladium 10 on activated carbon / methanol / 4 h 6.2: pH 3 With sodium tetrahydroborate, N-bromosuccinmide, copper(l) iodide, ethanol, palladium 10 on activated carbon, ammonium acetate, hydrogen, titanium tetrachloride, ethyl acetate in methanol, dichloromethane, chloroform, ethyl acetate, N,N-dimethyl-formamide, 3.1: |Rieche Formylation / 4.1: |Henry Nitro Aldol Condensation 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

H 13C 13CH HO

13C

13CH

H 13C 13CH

H 13C

13C

13C 13

13C

HCl

H H 2N

Rx-ID: 38014781 View in Reaxys 147/177 Yield

Conditions & References Reaction Steps: 7 1.1: sodium hydroxide / water / 0.5 h / |Inert atmosphere 1.2: 1 h / 0 - 50 °C / |Inert atmosphere 2.1: N-bromosuccinmide / chloroform; N,N-dimethyl-formamide / 70 °C 3.1: copper(l) iodide; ethyl acetate / N,N-dimethyl-formamide; methanol / 48 h / 80 °C / |Sealed tube; |Inert atmosphere 4.1: titanium tetrachloride / dichloromethane / 17 h / -5 - 4 °C / |Inert atmosphere 5.1: ammonium acetate / 2 h / 70 °C 6.1: sodium tetrahydroborate; ethanol / ethyl acetate / 1 h / 22 °C 7.1: hydrogen; palladium 10 on activated carbon / methanol / 4 h 7.2: pH 3 With sodium tetrahydroborate, N-bromosuccinmide, copper(l) iodide, ethanol, palladium 10 on activated carbon, ammonium acetate, hydrogen, titanium tetrachloride, ethyl acetate, sodium hydroxide in methanol, dichloromethane, chloroform, water, ethyl acetate, N,N-dimethyl-formamide, 4.1: |Rieche Formylation / 5.1: |Henry Nitro Aldol Condensation 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

H C 13C

13C

13CH

H 13C O

13C

HCl

H 2N

Rx-ID: 38014791 View in Reaxys 148/177 Yield

Conditions & References Reaction Steps: 5 1.1: copper(l) iodide; ethyl acetate / N,N-dimethyl-formamide; methanol / 48 h / 80 °C / |Sealed tube; |Inert atmosphere

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2.1: titanium tetrachloride / dichloromethane / 17 h / -5 - 4 °C / |Inert atmosphere 3.1: ammonium acetate / 2 h / 70 °C 4.1: sodium tetrahydroborate; ethanol / ethyl acetate / 1 h / 22 °C 5.1: hydrogen; palladium 10 on activated carbon / methanol / 4 h 5.2: pH 3 With sodium tetrahydroborate, copper(l) iodide, ethanol, palladium 10 on activated carbon, ammonium acetate, hydrogen, titanium tetrachloride, ethyl acetate in methanol, dichloromethane, ethyl acetate, N,N-dimethyl-formamide, 2.1: |Rieche Formylation / 3.1: |Henry Nitro Aldol Condensation 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

H 13C

13C

H 13C

13 13

C H

13C

HCl

H 2N

Rx-ID: 38014828 View in Reaxys 149/177 Yield

Conditions & References Reaction Steps: 4 1.1: titanium tetrachloride / dichloromethane / 17 h / -5 - 4 °C / |Inert atmosphere 2.1: ammonium acetate / 2 h / 70 °C 3.1: sodium tetrahydroborate; ethanol / ethyl acetate / 1 h / 22 °C 4.1: hydrogen; palladium 10 on activated carbon / methanol / 4 h 4.2: pH 3 With sodium tetrahydroborate, ethanol, palladium 10 on activated carbon, ammonium acetate, hydrogen, titanium tetrachloride in methanol, dichloromethane, ethyl acetate, 1.1: |Rieche Formylation / 2.1: |Henry Nitro Aldol Condensation 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 O

13C

H 13C

13C

13 13C

HCl

H 2N

Rx-ID: 38014833 View in Reaxys 150/177 Yield

Conditions & References Reaction Steps: 3 1.1: ammonium acetate / 2 h / 70 °C 2.1: sodium tetrahydroborate; ethanol / ethyl acetate / 1 h / 22 °C 3.1: hydrogen; palladium 10 on activated carbon / methanol / 4 h 3.2: pH 3 With sodium tetrahydroborate, ethanol, palladium 10 on activated carbon, ammonium acetate, hydrogen in methanol, ethyl acetate, 1.1: |Henry Nitro Aldol Condensation 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

H 13C O

13C

H O

13C 13C

H 13C O

N O

13C

13C 13C

O HCl

H H 2N

Rx-ID: 38014840 View in Reaxys 151/177

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Yield

Conditions & References Reaction Steps: 2 1.1: sodium tetrahydroborate; ethanol / ethyl acetate / 1 h / 22 °C 2.1: hydrogen; palladium 10 on activated carbon / methanol / 4 h 2.2: pH 3 With sodium tetrahydroborate, ethanol, palladium 10 on activated carbon, hydrogen in methanol, ethyl acetate 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 13

C H O

H 13C

13C

HCl

H 2N

Rx-ID: 38014843 View in Reaxys 152/177 Yield

Conditions & References

218 mg

Stage 1: With palladium 10 on activated carbon, hydrogen in methanol, Time= 4h Stage 2: With hydrogenchloride in methanol, pH= 3 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

O O

H 2N

Rx-ID: 41708099 View in Reaxys 153/177 Yield

Conditions & References Reaction Steps: 2 1: nitric acid / acetic acid / 1 h / 0 °C 2: triethylamine; sodium tris(acetoxy)borohydride / 1,2-DICHLOROETHANE / 2 h / 20 °C With nitric acid, sodium tris(acetoxy)borohydride, triethylamine in acetic acid, 1,2-DICHLOROETHANE Patent; Randox Laboratories Ltd.; Benchik, Elouard; Fitzgerald, Peter; Lowry, Philip; McConnell, Ivan; EP2950104; (2015); (A1) English View in Reaxys O

O O

O H 2N

N O

Rx-ID: 41708100 View in Reaxys 154/177 Yield

Conditions & References Reaction Steps: 3

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1: nitric acid / acetic acid / 1 h / 0 °C 2: triethylamine; sodium tris(acetoxy)borohydride / 1,2-DICHLOROETHANE / 2 h / 20 °C 3: triethylamine; dmap / dichloromethane / 20 °C With dmap, nitric acid, sodium tris(acetoxy)borohydride, triethylamine in dichloromethane, acetic acid, 1,2-DICHLOROETHANE Patent; Randox Laboratories Ltd.; Benchik, Elouard; Fitzgerald, Peter; Lowry, Philip; McConnell, Ivan; EP2950104; (2015); (A1) English View in Reaxys NH 2 O

H 2N

Rx-ID: 41708101 View in Reaxys 155/177 Yield

Conditions & References Reaction Steps: 3 1: nitric acid / acetic acid / 1 h / 0 °C 2: triethylamine; sodium tris(acetoxy)borohydride / 1,2-DICHLOROETHANE / 2 h / 20 °C 3: ammonium formate; 5 palladium on charcoal / methanol / 2 h / 20 °C With 5 palladium on charcoal, nitric acid, ammonium formate, sodium tris(acetoxy)borohydride, triethylamine in methanol, acetic acid, 1,2-DICHLOROETHANE Patent; Randox Laboratories Ltd.; Benchik, Elouard; Fitzgerald, Peter; Lowry, Philip; McConnell, Ivan; EP2950104; (2015); (A1) English View in Reaxys

O O

O O O

O O

N H

H N

H 2N

Rx-ID: 145362 View in Reaxys 156/177 Yield

Conditions & References Phillips; Journal of the American Chemical Society; vol. 75; (1953); p. 3621 View in Reaxys

H N

H 2N

Rx-ID: 145363 View in Reaxys 157/177 Yield

Conditions & References Phillips; Journal of the American Chemical Society; vol. 75; (1953); p. 3621 View in Reaxys

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Cl O

H N

O O

H 2N

Rx-ID: 796400 View in Reaxys 158/177 Yield

Conditions & References Phillips; Journal of the American Chemical Society; vol. 75; (1953); p. 3621 View in Reaxys

H N

H 2N

Rx-ID: 4560799 View in Reaxys 159/177 Yield

Conditions & References T= 80 - 100 °C Cantrell, Amanda S.; Engelhardt, Per; Hoegberg, Marita; Jaskunas, S. Richard; Johansson, Nils Gunnar; Jordan, Christopher L.; Kangasmetsae, Jussi; Kinnick, Michael D.; Lind, Peter; Morin Jr., John M.; Muesing; Noreen, Rolf; Oeberg, Bo; Pranc, Paul; Sahlberg, Christer; Ternansky, Robert J.; Vasileff, Robert T.; Vrang, Lotta; West, Sarah J.; Zhang, Hong; Journal of Medicinal Chemistry; vol. 39; nb. 21; (1996); p. 4261 - 4274 View in Reaxys

H N

N O

O O

H 2N

Rx-ID: 8997798 View in Reaxys 160/177 Yield

Conditions & References

35 %

in tetrahydrofuran, Time= 120h, Heating Koike, Takeshi; Takeuchi, Naoki; Chemical and Pharmaceutical Bulletin; vol. 50; nb. 4; (2002); p. 484 - 488 View in Reaxys Cl

H N

H 2N

H N

Rx-ID: 9870584 View in Reaxys 161/177 Yield

Conditions & References in acetonitrile, Time= 20h, T= 100 °C Venkatachalam; Uckun, Faith M.; Synthetic Communications; vol. 35; nb. 15; (2005); p. 2039 - 2056 View in Reaxys

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F H N

H N S

H 2N

Rx-ID: 9870585 View in Reaxys 162/177 Yield

Conditions & References in acetonitrile, Time= 20h, T= 100 °C Venkatachalam; Uckun, Faith M.; Synthetic Communications; vol. 35; nb. 15; (2005); p. 2039 - 2056 View in Reaxys

H N

H N S

H 2N

Rx-ID: 9870586 View in Reaxys 163/177 Yield

Conditions & References in acetonitrile, Time= 20h, T= 100 °C Venkatachalam; Uckun, Faith M.; Synthetic Communications; vol. 35; nb. 15; (2005); p. 2039 - 2056 View in Reaxys

Cl H N

H N

S O

H 2N

Rx-ID: 9870587 View in Reaxys 164/177 Yield

Conditions & References in acetonitrile, Time= 20h, T= 100 °C Venkatachalam; Uckun, Faith M.; Synthetic Communications; vol. 35; nb. 15; (2005); p. 2039 - 2056 View in Reaxys

O O

H 2N

Rx-ID: 22015848 View in Reaxys 165/177 Yield

Conditions & References Reaction Steps: 2 1: amyl alcohol; hydrazine hydrate 2: beim Erwaermen des hergestellten Azids in Benzol und Erwaermen des Reaktionsprodukts mit wss. Salzsaeure With pentan-1-ol, hydrazine hydrate Leaf; Neuberger; Biochemical Journal; vol. 43; (1948); p. 606,608; Biochemical Journal; vol. 57; (1954); p. 528 View in Reaxys

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O N

O H 2N

O racemate

Rx-ID: 38487407 View in Reaxys 166/177 Yield

Conditions & References Reaction Steps: 2 1.1: ammonium cerium (IV) nitrate / ethanol / 0.5 h / |Reflux 1.2: 0.5 h / |Reflux 2.1: acetic acid; sodium tetrahydroborate / 2 h / 15 - 20 °C With sodium tetrahydroborate, ammonium cerium (IV) nitrate, acetic acid in ethanol, 1.1: |Hantzsch Dihydropyridine Synthesis / 1.2: |Hantzsch Dihydropyridine Synthesis Suryavanshi, Padmakar A.; Sridharan, Vellaisamy; Maiti, Swarupananda; Menendez, J. Carlos; Chemistry - A European Journal; vol. 20; nb. 28; (2014); p. 8791 - 8799 View in Reaxys

O O

N H

E Z

N H

H 2N

H N

O O

O NH 2

Rx-ID: 39427202 View in Reaxys 167/177 Yield

Conditions & References in dichloromethane, T= 20 °C Li, Zhenyu; Jia, Lejiao; Wang, Jifeng; Wu, Xingkang; Shi, Guowei; Lu, Chunhua; Shen, Yuemao; Chemical Biology and Drug Design; vol. 85; nb. 2; (2015); p. 181 - 188 View in Reaxys 2H

NH 2 2H 2H

NH 2

O 2H

Rx-ID: 11289584 View in Reaxys 168/177 Yield 24 %

Conditions & References With bromine, acetic acid Xu, Ya-Zhu; Chen, Chinpiao; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 49; nb. 13; (2006); p. 1187 - 1200 View in Reaxys

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H N

[14C]acetyl-CoA

H 2N

Rx-ID: 8807125 View in Reaxys 169/177 Yield

Conditions & References With sheep pineal supernatant (serotonin-N-acetyl transferase), N-methyl-N-propargyl benzyl amine in phosphate buffer, Time= 0.166667h, T= 37 °C , pH= 6.8, Enzyme kinetics Shen, Shuren; Bremont, Beatrice; Serraz, Isabelle; Andrieux, Jean; Poncet, Annie; Mathe-Allainmat, Monique; Chanut, Evelyne; Trouvin, Jean-Hugues; Langlois, Michel; European Journal of Pharmacology; vol. 307; nb. 2; (1996); p. 133 - 140 View in Reaxys

H O

H 2N

Rx-ID: 2678319 View in Reaxys 170/177 Yield

Conditions & References in benzene, Heating Kubo, Akinori; Saito, Naoki; Kawakami, Nanko; Matsuyama, Yasuo; Miwa, Teruyo; Synthesis; nb. 9; (1987); p. 824 - 827 View in Reaxys O

H N

O O

H 2N

Rx-ID: 14915726 View in Reaxys 171/177 Yield

Conditions & References Reaction Steps: 2 1: 35 percent / tetrahydrofuran / 120 h / Heating 2: 44 percent / xylene / 5 h / Heating in tetrahydrofuran, xylene Koike, Takeshi; Takeuchi, Naoki; Chemical and Pharmaceutical Bulletin; vol. 50; nb. 4; (2002); p. 484 - 488 View in Reaxys

O O

H 2N

O O

Rx-ID: 14915727 View in Reaxys 172/177 Yield

Conditions & References Reaction Steps: 2 1: 35 percent / tetrahydrofuran / 120 h / Heating

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2: 25 percent / xylene / 5 h / Heating in tetrahydrofuran, xylene Koike, Takeshi; Takeuchi, Naoki; Chemical and Pharmaceutical Bulletin; vol. 50; nb. 4; (2002); p. 484 - 488 View in Reaxys

O O

N O

H 2N

Rx-ID: 22214449 View in Reaxys 173/177 Yield

Conditions & References Reaction Steps: 2 2: phosphoryl chloride; benzene With trichlorophosphate, benzene Sugasawa; Shigehara; Chemische Berichte; vol. 74; (1941); p. 459,462 View in Reaxys

O H 2N

H 2N

Rx-ID: 488020 View in Reaxys 174/177 Yield

Conditions & References beim Erwaermen des hergestellten Azids in Benzol und Erwaermen des Reaktionsprodukts mit wss. Salzsaeure Leaf; Neuberger; Biochemical Journal; vol. 43; (1948); p. 606,608; Biochemical Journal; vol. 57; (1954); p. 528 View in Reaxys

O O

O H 2N

Rx-ID: 1738416 View in Reaxys 175/177 Yield

Conditions & References in benzene, Heating Freeman, Jeremiah P.; Fettes-Fields, Mary Kay; Heterocycles; vol. 23; nb. 5; (1985); p. 1073 - 1076 View in Reaxys

O Z

H N

H 2N

Rx-ID: 5214585 View in Reaxys 176/177 Yield

Conditions & References in tetrahydrofuran, Time= 5h, Ambient temperature, Title compound not separated from byproducts Koike, Takeshi; Takeuchi, Naoki; Tobinaga, Seisho; Chemical and Pharmaceutical Bulletin; vol. 47; nb. 1; (1999); p. 128 - 130

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View in Reaxys

O H 2N

Rx-ID: 6590942 View in Reaxys 177/177 Yield

Conditions & References Patent; Polaroid Corp.; US3062884; (1955); ; vol. 58; nb. 5575d; (1963) View in Reaxys D. Similarly, replacing 3-methoxyphenethylamine with: 3,4-dimethoxyphenethylamine; 2,5-dimethoxyphenethylamine; 3,4-(ethylene-1,2-dioxy)phenethylamine; 2-methylphenethylamine; 3-methylphenethylamine; 4-methylphenethylamine; 3-ethylphenethylamine; 3,4-dimethylphenethylamine; 3-isobutylphenethylamine; ... Patent; Syntex (U.S.A.) Inc.; US5231181; (1993); (A1) English View in Reaxys

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