2-(1H-indol-3-yl)ethan-1-amine [Tryptamine] by Asch

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87 reactions in Reaxys

2016-06-21 14h:35m:59s (EST)

87 reactions in Reaxys

2016-06-21 14h:38m:07s (EST)

NH 2

1. Query NH

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(1. Query) AND itemno in (2,1)

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NH 2

Rx-ID: 5427225 View in Reaxys 1/87 Yield 81 %

Conditions & References 2.5 : EXAMPLE 2 Deacylation using ethylene diamine General procedure: EXAMPLE 2 Deacylation using ethylene diamine (No.1) [0040] As shown by the reaction equation below, deacylation reaction was carried out with different types of amides as listed in Table 6-1 and Table 6-2. To 1.0 mmol of each amide and 1.0 equiv. of ammonium bromide was added 266 µL (4.0 equiv.) of ethylenediamine, followed by the reaction under microwave irradiation. The respective reaction conditions and product identification data (1H NMR data and 13C NMR data) are set out later together with the reaction equations. [Table 6-1] Entry No. Amide Reaction Temperature(°C) Reaction Time(hr.) Yield (percent)a 1 80 5 90 80 10 79b,c 90 10 90b,c 2 80 10 93 3 100 10 88 4 80 5 89 5 80 5 81(89°) 6 80 5 98 7 70 5 >99 8 70 5 >99 9 70 5 81(>99°) 10 70 5 97 11 70 5 >99 12 70 5 >99 12 70 5 96 13 70 5 99 14 70 5 99 a: Isolation Yield b: Ammonium bromide was 10molpercent. c: The yield was determined by 1H NMR analysis of the reaction mixture. [Table 6-2] Entry No Amide Reaction Temperature(°C) Reaction Time(hr) Yield (percent)a 15 70 5 93 16 70 5 83 17 70 5 >99 18 80 10 95 19 100 15 95b 20 100 5 93 21 80 10 97 22 100 5 87 23 90 5 94 24 60 5 91 25 80 5 89h 26 60 3 >99b 80 +3 27 50 5 87 28 50 5 96 a Isolation Yield b: Ammonium bromide was 10molpercent. Dichloromethane and 1 M hydrochloric acid aqueous solution were added to the reaction mixture for separation with separatory funnel. The aqueous layer was basified with sodium hydroxide aqueous solution, followed by the extraction of the target amine with ether. The organic layer was dried over sodium sulfate, and then the solvent was removed by rotary evaporation to obtain a yellow liquid product. Yield 96.6 mg (90percent). 1H NMR (400 MHz, CDCl3) δ 7.38-7.22 (m, 5H), 3.87 (s, 2H), 1.56 (br, 2H); 13C NMR (100 MHz, CDCl3) δ 143.14, 128.51, 127.02, 126.77, 46.41. With NH4Br, ethylenediamine, Time= 5h, T= 80 °C , Microwave irradiation Patent; Kyushu University, National University Corporation; OHSHIMA Takashi; MORIMOTO Hiroyuki; SHIMIZU Yuhei; EP2821389; (2015); (A1) English View in Reaxys

80%

12 : EXAMPLE 12 EXAMPLE 12 In a 100L separator, the amine solution (12) in toluene (190 mg /mL, 45L) was heated to about 55° C. under nitrogen. 4-Vinyl pyridine (7.84 kg) was added followed by acetic acid (2.67L). The batch was then heated to about 80° C. and aged for about two hours. The batch was cooled to about 50° C. and washed with aqueous sodium hydroxide (2.5M, 20L final pH 13.0-14.0). The aqueous layer was separated and the organic layer was washed with water (16L*2) at about 50° C. The batch was then concentrated and solvent was switched to methanol and then to ethyl acetate. The mixture was seeded and was allowed to age for about 24 hours prior to filtering. The cake was washed with ethyl acetate (0° C., 15L) to give the final product (13) (yield 80percent). Patent; Chung, John Y. L.; Farr, Roger N.; Humphrey, Guy R.; US2003/13876; (2003); (A1) English View in Reaxys

48%

1 : Preparation of β-Methylmelatonin The above crude amino acid was immediately decarboxylated by refluxing in 150 ml of 5M methane-sulfonic acid under nitrogen for 47 minutes. After cooling, the solution was made basic by the addition of 5M aqueous NaOH. The decarboxylated product was extracted into ether. The ether extracts were dried over Na2 SO4. Evaporation of the ether gave 3.92 g of crude tryptamine as a gummy solid. Washing the crude material with a small amount of cold toluene gave 2.48 g of crystalline product (48percent yield) comprising purified 5-methoxy-3-(1-amino-2-propyl)indole. Patent; Eli Lilly and Company; US4997845; (1991); (A1) English View in Reaxys

43.5%

69.G : PREPARATION OF 9-FLUORO-3-(3,4-DIFLUORO-BENZOYL)-1,1-DIMETHYL-1,2,3,6-TETRAHYDROAZEPINO[4,5-B]INDOLE-5-CARBOXYLIC ACID ISOPROPYL ESTER G.

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The solution of crude tryptamine obtained from step F (9.69 mmol), HCl (Aldrich, 4M in dioxane, 2.7 mL, 10.7 mmol), and charcoal (Aldrich, 2.0 9) in 60 mL of PrOH was treated with isopropyl bromopyruvate (home made, 5.26 g, 25.2 mmol) at room temperature under Ar for 10 minutes. The reaction mixture was heated at 91° C. reflux for 16 hours and then cooled to room temperature. The solvent was removed in vacuo. To the above residue, 21 mL of pyridine was added at room temperature. The reaction mixture was heated at 105° C. reflux under Ar for 16 hours, and then the solvent was removed in vacuo. MeOH (50 mL) was added, and the solution was filtered and concentrated. The crude product was purified by flash chromatograph on silica gel, eluding with CH2Cl2-hexane (0-80percent) to yield the indoleazepine product (1.34 9, 43.5percent yield) as a light yellow solid. 1H-NMR (CDCl3): δ 11.01 (1H, s), 7.87 (1H, d), 7.39 (1H, d), 7.19 (1H, m), 6.78 (1H, m), 5.32 (1H, s), 5.15 (1H, m), 3.27 (2H, s), 1.52 (6H, s), 1.29 (6H, d). MS (ESI): 317 (MH+). Patent; Busch, Brett; Flatt, Brenton T.; Gu, Xiao-Hui; Martin, Richard; Mohan, Raju; Wang, Tie-Lin; Wu, Jason H.; US2005/54634; (2005); (A1) English View in Reaxys 38%

5.4 : 3. 4-Chlorobutanal dimethylacetal (3.22 g, 21.1 mmol) was added to a stirred solution of the preceding hydrazine (5.0 g, 26.4 mmol) in ethanol/water (5:1, 180 ml) and 5N HCl (4.5 ml) and the solution refluxed for 4 h. The solvents were removed under vacuum and the residue chromatographed on silica gel, eluding with CH2 Cl2 / EtOH/NH3 (30:8:1) to give the desired tryptamine (2.4 g, 38percent). δ(360 MHz, CDCl3) 2.90 (2H, t, J=7 Hz, CH2), 2.99 (2H, t, J=7 Hz, CH2), 5.43 (2H, s, CH2), 7.10 (1H, s, Ar-H), 7.11 (1H, d, J=8Hz, Ar-H), 7.39 (1H, d, J=8Hz, Ar-H), 7.57 (1H, s, Ar-H), 7.94 (1H, s, Ar-H), 8.08 (1H, s, Ar-H). Patent; Merck Sharp and Dohme Limited; US5298520; (1994); (A1) English View in Reaxys Adlerova,E. et al.; Collection of Czechoslovak Chemical Communications; vol. 25; (1960); p. 784 - 796 View in Reaxys Konda; Suzuki; Omura; Onda; Chemical and Pharmaceutical Bulletin; vol. 24; nb. 1; (1976); p. 92 - 96 View in Reaxys Bergman,J. et al.; Tetrahedron; vol. 29; (1973); p. 971 - 976 View in Reaxys Pfeil,E.; Harder,U.; Angewandte Chemie; vol. 79; (1967); p. 188 View in Reaxys Fleming,I.; Woolias,M.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1979); p. 829 - 837 View in Reaxys Jeffreys,J.A.D.; Journal of the Chemical Society [Section] C: Organic; (1970); p. 1091 - 1103 View in Reaxys de Groot,S.; Strating,J.; Recueil des Travaux Chimiques des Pays-Bas; vol. 80; (1961); p. 121 - 133 View in Reaxys Patent; Buzas; Lavielle; FR2338259; (1977); ; vol. 88; nb. 120984 View in Reaxys Julia; Manoury; Bulletin de la Societe Chimique de France; (1965); p. 1411,1413 View in Reaxys Julia et al.; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 251; (1960); p. 394 View in Reaxys Ahmad et al.; Canadian Journal of Chemistry; vol. 38; (1960); p. 2523 View in Reaxys Matkovics et al.; Acta Physica et Chemica; vol. 7; (1961); p. 51 View in Reaxys Avramenko et al.; Pharmaceutical Chemistry Journal; nb. 12; (1970); p. 671; Khimiko-Farmatsevticheskii Zhurnal; nb. 12; (1970); p. 10 View in Reaxys Heinzelman; Szmuszkovicz; Progress in Drug Research; vol. 6; (1963); p. 75,76-150; ; vol. 60; nb. 13215b; (1964) View in Reaxys Buzas et al.; Synthesis; (1977); p. 129 View in Reaxys Ganellin et al.; Journal of the Chemical Society [Section] C: Organic; (1967); p. 2220 View in Reaxys

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Hasselmann et al.; Photochemistry and Photobiology; vol. 27; (1978); p. 13,14 View in Reaxys Grandberg et al.; Doklady Chemistry; vol. 176; (1967); p. 828; Doklady Akademii Nauk SSSR; vol. 176; (1967); p. 583 View in Reaxys Bocourt; Vignau; Bulletin de la Societe Chimique de France; (1961); p. 1190 View in Reaxys Patent; Richter Gedeon Vegyeszeti Gyar R.T.; FR2261271; (1973); DE2344919; ; vol. 80; nb. 146016 View in Reaxys Kametani et al.; Synthesis; (1972); p. 475 View in Reaxys Patent; Grandberg; Bobrowa; SU451696; (1976); Ref. Zh., Khim.; vol. 8; nb. O143P; (1976) View in Reaxys Patent; Lab.francais de chimiotherapie; US2920080; (1960); ; vol. 54; nb. 13018hi; (1960) View in Reaxys Patent; Nikhon kemifa h.h; JP5230513; (1977); Ref. Zh., Khim.; vol. 15; nb. O150P; (1978) View in Reaxys Suvorov et al.; Chemistry of Heterocyclic Compounds (New York, NY, United States); vol. 10; (1974); p. 1316,1320; Khimiya Geterotsiklicheskikh Soedinenii; vol. 10; (1974); p. 1496 View in Reaxys Szantay et al.; Synthesis; (1974); p. 354 View in Reaxys Barton et al.; Journal of the Chemical Society; (1965); p. 3990,3993 View in Reaxys Peter; Rajewsky; Z. Naturforsch., B: Anorg. Chem., Org. Chem., Biochem., Biophys.,; vol. 18; (1963); p. 110 View in Reaxys Grandberg et al.; Sintezy Geterotsiklicheskikh Soedinenii; vol. 9; (1972); p. 18; ; vol. 79; nb. 146321 View in Reaxys Grandberg; Bobrova; Chemistry of Heterocyclic Compounds (New York, NY, United States); vol. 9; (1973); p. 196,199; Khimiya Geterotsiklicheskikh Soedinenii; vol. 9; (1973); p. 213 View in Reaxys Grandberg; Bobrova; Chemistry of Heterocyclic Compounds (New York, NY, United States); vol. 10; (1974); p. 943; Khimiya Geterotsiklicheskikh Soedinenii; vol. 10; (1974); p. 1085 View in Reaxys Suvorov et al.; J. Gen. Chem. USSR (Engl. Transl.); vol. 45; (1975); p. 1600,1565,1568 View in Reaxys Mndzhoyan; Papayan; Izvestiya Akademii Nauk Armyanskoi SSR, Khimicheskie Nauki; vol. 14; (1961); p. 603; ; vol. 58; nb. 4497c; (1963) View in Reaxys Julia; Lallemand; Bulletin de la Societe Chimique de France; (1973); p. 2058,2059, 2061 View in Reaxys Takano et al.; Heterocycles; vol. 6; (1977); p. 1167,1168, 1169, 1170 View in Reaxys Kametani et al.; Yakugaku Zasshi; vol. 95; (1975); p. 363,366; ; vol. 83; nb. 193572 View in Reaxys Piozzi; Merlini; Gazzetta Chimica Italiana; vol. 92; (1962); p. 1105,1107-1116 View in Reaxys Tacconi; Farmaco, Edizione Scientifica; vol. 20; (1965); p. 891,895,899 View in Reaxys Patent; President and Fellows of Harvard College; US2005/4156; (2005); (A1) English View in Reaxys Condensation product of melamine and p-aminophenol ... Thiazolsulfone (Promizole, 5-[(4-aminophenyl)sulfonyl]-2-thiazolamine) 18. Thioguanine 19. 3,5-Diamino-1,2,4-triazole 20. Piperazine 21. Tryptamine Maleic hydrazide Barbituric acid

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3. Barbital ... Patent; Schmitz, Robert A.; US6299892; (2001); (B1) English View in Reaxys 1.ii : (ii) (ii) 3-(2-Aminoethyl)-N-[(4-methoxyphenyl)methyl]-1H-indole-5-methanesulphonamide hemisuccinate A suspension of the product of Stage (i) (0.2 g) and rhodium on alumina (5percent; 0.25 g) in methanolic ammonia (15 ml) was hydrogenated at atmospheric pressure and room temperature for 5 h. The catalyst was filtered off (Hyflo), washed with ethanol (20 ml), the solvent evaporated and the residue purified by column chromatography (A) then (B) to give the tryptamine as an oil (0.19 g). Patent; Glaxo Group Limited; US4894387; (1990); (A1) English View in Reaxys 10.ii : (ii) (ii) N-[(4-Methoxyphenyl)methyl]-N-methyl-3-[2-(methylamino)ethyl]-1H-indole-5-methanesulphonamide compound with succinic acid (3:1) A solution of the product of Stage (i) (0.42 g) in ethanolic methylamine (20 ml, 30percent w/w) was hydrogenated over pre-reduced 10percent palladium oxide on charcoal (50percent paste with water 0.7 g) in ethanol (5 ml) for 18 h. The suspension was filtered through hyflo and the filtrate was evaporated in vacuo to give an oil (0.4 g). Column chromatography (A) gave the tryptamine (193 mg) which was dissolved in absolute ethanol (2 ml) and treated with a solution of succinic acid (0.28 g) in ethanol (0.5 ml). Patent; Glaxo Group Limited; US4894387; (1990); (A1) English View in Reaxys 12 : 3-[2-(Dimethylamino)ethyl]-N-[2-(4-methoxyphenyl)ethyl]-1H-indole-5-methanesulphonamide hemisuccinate hydrate EXAMPLE 12 3-[2-(Dimethylamino)ethyl]-N-[2-(4-methoxyphenyl)ethyl]-1H-indole-5-methanesulphonamide hemisuccinate hydrate A solution of Example 4 Stage (i) (0.3 g) in ethanolic dimethylamine (20 ml 30 w/w) was hydrogenated over prereduced 10percent palladium oxide on charcoal (0.6 g, 50percent paste with water) in ethanol (5 ml) for 48 h. The suspension was filtered through hyflo and the filtrate evaporated in vacuo to give an oil (0.27 g). Column chromatography (A) gave the tryptamine as an oil (176 mg). Patent; Glaxo Group Limited; US4894387; (1990); (A1) English View in Reaxys 3 : 3-[2-(Dimethylamino)ethyl]-N-[(4-methoxyphenyl)methyl]-1H-indole-5-methanesulphonamide, hemisuccinate EXAMPLE 3 3-[2-(Dimethylamino)ethyl]-N-[(4-methoxyphenyl)methyl]-1H-indole-5-methanesulphonamide, hemisuccinate A solution of the product of Example 1 Stage (i) (0.35 g) in ethanolic dimethylamine (20 ml; 33percent w/w) was hydrogenated over prereduced 10percent palladium oxide on charcoal (0.6 g; 50percent paste with water) in ethanol (5 ml) for 3 h. The catalyst was removed by filtration, the filtrate concentrated and the residue chromatographed (D) to give the tryptamine as a foam (0.25 g). Patent; Glaxo Group Limited; US4894387; (1990); (A1) English View in Reaxys 4.ii : (ii) (ii) 3-(2-Aminoethyl)-N-[(4-methoxyphenyl)ethyl]-1H-indole-5-methanesulphonamide hemisuccinate A solution of the product of Stage (i) (0.35 g) in methanolic ammonia (20 ml) was hydrogenated over 5percent rhodium on alumina (0.4 g) for 3 h. The catalyst was filtered off (Hyflo), washed with ethanol (50 ml), and the solvent evaporated. The residue was chromatographed (D) to give the tryptamine as a foam (0.35 g).

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Patent; Glaxo Group Limited; US4894387; (1990); (A1) English View in Reaxys 7.iv : (iv) (iv) 3-(2-Aminopropyl)-N-methyl-1H-indole-5-ethanesulphonamide hydrochloride A solution of the product of Stage (iii) (0.43 g) in ethanol (50 ml), was hydrogenated over pre-reduced 10percent palladium oxide on charcoal (0.4 g) for 75.5h at atmospheric pressure and temperature. The reaction mixture was filtered and evaporated in vacuo to give an oil (0.27 g) which was chromatographed (A, 3 cm dia. col.) to give the tryptamine as an oil (0.23 g). Patent; Glaxo Group Limited; US4994483; (1991); (A1) English View in Reaxys 7 : 3-[2-(Ethylamino)ethyl]-N-[2-(4-methoxyphenyl)ethyl]-1H-indole-5-methanesulphonamide hemisuccinate hemihydrate EXAMPLE 7 3-[2-(Ethylamino)ethyl]-N-[2-(4-methoxyphenyl)ethyl]-1H-indole-5-methanesulphonamide hemisuccinate hemihydrate A solution of the product of Example 4 Stage (i) (0.35 g) in ethanolic ethylamine (20 ml; 30percent w/w) was hydrogenated over pre-reduced 10percent palladium oxide on charcoal (50percent paste with water, 0.6 g) in ethanol (5 ml) for 3 h. The suspension was filtered through hyflo and the filtrate was evaporated to give an oil (0.29 g). Column chromatography (A) gave the tryptamine as a foam (0.15 g). Patent; Glaxo Group Limited; US4894387; (1990); (A1) English View in Reaxys 9.ii : (ii) (ii) N-[(3-Methoxyphenyl)methyl]-3-[2-(methylamino)ethyl]-1H-indole-5-methanesulphonamide compound with succinic acid (10:6) A solution of the product of Stage (i) (0.3 g) in ethanolic methylamine (20 ml, 30percent w/w) was hydrogenated over pre-reduced 10percent palladium oxide on charcoal (50percent paste with water, 0.3 g) in ethanol for 24 h. The suspension was filtered through hyflo and the filtrate evaporated in vacuo to give a oil (0.3 g) which was chromatographed (A) to give the tryptamine as an oil (145 mg). This oil was dissolved in absolute ethanol (2 ml) and succinic acid (22 mg) was added. Patent; Glaxo Group Limited; US4894387; (1990); (A1) English View in Reaxys Method (VI) Method (VI) A solution of the product of Example 1 as the free base (0.4 g) in n-propanol (16 ml), chilled in an ice-bath was treated with aqueous formaldehyde (~40percent soln, 0.64 ml) and the resultant suspension stirred for 0.75 h, under an atmosphere of nitrogen. Sodium borohydride (0.54 g) was added and the resulting mixture stirred in an ice-bath for 2 h. The suspension was treated with 2N hydrochloric acid (~6 ml), and stirred for 10 min. The resulting mixture was evaporated to low volume (keeping the temperature below (50°) basified with 8percent aq. sodium bicarbonate solution (20 ml) and extracted with ethyl acetate (5*15 ml). The combined extracts were dried (MgSO4) and evaporated to produce an oil (0.35 g) which was chromatographed (B) to give the tryptamine as an oil (0.148 g). Patent; Glaxo Group Limited; US4994483; (1991); (A1) English View in Reaxys 8.ii : ii) ii) 3-[2-(Dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide, compound with succinic acid (2:1) A mixture of polyphosphate ester (20 g) and the product of Stage (i) (4 g) in chloroform (80 ml) was stirred at room temperature for 4 h. The reaction mixture was extracted with water (2*100 ml), the aqueous extracts washed with chloroform (50 ml), then basified to pH 11 with solid potassium carbonate and extracted with ethyl acetate (3*100 ml).

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The combined organic extracts were dried (MgSO4) and concentrated in vacuo to leave a foam (2.5 g), which was chromatographed (F) to give the tryptamine as an oil (1.13 g) which slowly crystallized on standing. Patent; Glaxo Group Limited; US5037845; (1991); (A1) English View in Reaxys 1.iii : (ii) (iii) 3-(2-Aminoethyl)-1H-indole-5-acetic acid, methyl ester, compound with creatinine, sulphuric acid and water (1:1:1:1.25) A solution of 3-[2-(1,3-dihydro-1,3-dioxo-2H-indol-2-yl)ethyl]-1H-indole-5-acetic acid, methyl ester (1.4 g) in ethanol (75 ml) was stirred at room temperature under nitrogen with 33percent ethanolic methylamine (15 ml) for 1.5 h. The solvent was removed under reduced pressure and the residual brown oil was purified by column chromatography (Whatman MFC, silica, 100 g). Elution with ethyl acetate:propan-2-ol:water:ammonia (25:15:8:2) gave the tryptamine (0.2 g) and a second crop (0.4 g) contaminated with a non-basic impurity. Patent; Glaxo Group Limited; US4650810; (1987); (A1) English View in Reaxys 4.i : (i) (i) 3-[2-[(Phenylmethyl)amino]ethyl]-1H-indole-5-acetamide compound with maleic acid (1:1) Benzaldehyde (1.4 g) was added to 3-(2-aminoethyl)-1H-indole-5-acetamide (2.8 g), in a mixture of benzene and ethanol (5:1, 40 ml) at room temperature. The resulting solution was evaporated to dryness in vacuo after 2.5 h and the residue was dissolved in absolute ethanol (75 ml). Sodium borohydride (0.5 g) was added in portions over 10 min at room temperature with stirring. After 7 h at room temperature acetic acid (2 ml) was added and the mixture was stirred overnight and then evaporated. The residue was chromatographed on silica gel (Merck type 60, 260 g) eluding with methanol in chloroform (1-25percent). The combined product-bearing fractions were evaporated and dissolved in chloroform (300 ml) and washed with 8percent aqueous sodium hydrogen carbonate (2.75 ml). The chloroform solution was dried (Na2 SO4), filtered and evaporated to give the tryptamine as a yellow glass (2.5 g). Patent; Glaxo Group Limited; US4650810; (1987); (A1) English View in Reaxys 1.c : (c) (c) 3-(2-Aminoethyl)-N-methyl-1H-indole-5-methanesulphonamide, maleate A solution of 4-Hydrazino-N-methylbenzenemethanesulphonamide hydrochloride (10 g) and 4-chlorobutanal dimethyl acetal (6.5 g) in ethanol/water (5:1, 500 ml) was heated at reflux for 2 h. The solution was then cooled and evaporated to dryness under reduced pressure. The orange-brown residue was purified by column chromatography (B) to give the tryptamine as an oil (3.9 g). Patent; Glaxo Group Limited; US4816470; (1989); (A1) English View in Reaxys 12.c : (c) (c) 3-(2-Aminoethyl)-N,N-dimethyl-1H-indole-5-methanesulphonamide, maleate A solution of the product of stage (b) (1 g) and 4-chlorobutanal, dimethyl acetal (0.7 g) in ethanol:water (5:1, 50 ml) was heated at reflux for 1 h 40 min. The cooled solution was evaporated to dryness under reduced pressure. The red-brown residue was purified by column chromatography (B) to give the tryptamine as an oil (0.13 g). Patent; Glaxo Group Limited; US4816470; (1989); (A1) English View in Reaxys 16.c : (c) (c)

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3-(2-Aminoethyl)-N-ethyl-1H-indole-5-methanesulphonamide maleate hemihydrate compound with diethylether (10:10:5:1) A solution of the product of stage (b) (0.425 g) and 4-chlorobutanal dimethyl acetal (0.244 g) in ethanol-water (5:1) (20 ml) was stirred at 50° for 40 min. Ammonium acetate (0.7394 g) was added and then the pH of the solution adjusted to pH 4 by hydrochloric acid. The resultant solution was heated under reflux for 2 h. The pale brown mixture was diluted water (200 ml) and washed with ethyl acetate (3*100 ml). The aqueous solution was basified with potassium carbonate (solid) and then extracted with ethyl acetate (4*100 ml). Subsequent evaporation of the dried (MgSO4) organic extracts yielded a brown foam (0.38 g) which was purified by chromatography (N) to give the tryptamine as a pale brown gum (0.1435 g). Patent; Glaxo Group Limited; US4816470; (1989); (A1) English View in Reaxys 16 : 5-(4,5-Dihydro-1H-imidazol-2-yl)-1H-indole-3-ethanamine dimaleate EXAMPLE 16 5-(4,5-Dihydro-1H-imidazol-2-yl)-1H-indole-3-ethanamine dimaleate A mixture of Intermediate 4 (1.5 g), ethylene diamine (0.44 g) and potassium carbonate (1.35 g) in dry ethanol (75 ml) was stirred under a nitrogen atmosphere for 20 h. The mixture was concentrated to dryness and the residue was absorbed onto alumina. Elution (B) afforded the tryptamine as an oil. Patent; Glaxo Group Limited; US4833153; (1989); (A1) English View in Reaxys 2.c : (c) (c) 3-(2-Aminoethyl)-N-methyl-1H-indole-5-methanesulphonamide, maleate A solution of the product of stage (b) (0.85 g) in methanol (10 ml) was hydrogenated over pre-reduced palladium oxide on carbon (10percent, 300 mg) at room temperature and atmospheric pressure for 6 h (uptake of hydrogen 30 ml). The catalyst was filtered off (hyflo) and washed with methanol (100 ml). The filtrate was concentrated and the residual white solid (0.56 g) purified by column chromatography (F) to give the tryptamine as a white foam (0.26 g). Patent; Glaxo Group Limited; US4816470; (1989); (A1) English View in Reaxys 21 : 3-[2-(Dimethylamino)ethyl]-1H-indole-5-methanesulphonamide, hydrochloride, compound with isopropanol (10:10:1.5) Example 21 3-[2-(Dimethylamino)ethyl]-1H-indole-5-methanesulphonamide, hydrochloride, compound with isopropanol (10:10:1.5) A solution of the product of example 19(b) (0.2 g) in methanolic dimethylamine (1:1, 20 ml) was hydrogenated over pre-reduced 10percent palladium oxide on charcoal (0.4 g, 50percent aqueous paste) in methanol (10 ml) at room temperature and atmospheric pressure for 5 h. The catalyst was removed by filtration (hyflo) and the filtrate was concentrated to an oil. Chromatography (B) gave the tryptamine as a white foam (0.16 g). Patent; Glaxo Group Limited; US4816470; (1989); (A1) English View in Reaxys 22 : N-Methyl-3-[2-(methylamino)ethyl]-1H-indole-5-methanesulphonamide, compound with maleic acid and ethanol (10:10:1) Example 22 N-Methyl-3-[2-(methylamino)ethyl]-1H-indole-5-methanesulphonamide, compound with maleic acid and ethanol (10:10:1) A solution of the product of example 2(b) (0.9 g) in dry tetrahydrofuran (20 ml) was added to a suspension of lithium aluminium hydride (0.9 g) in dry tetrahydrofuran (100 ml) and heated for 2 h at reflux. The resulting suspension was cooled, treated with a saturated solution of potassium carbonate (ice cooling), extracted with methanol (3*25 ml) and the extract concentrated. The residual oil was purified by column chromatography (K) to give the tryptamine as an oil (0.37 g).

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Patent; Glaxo Group Limited; US4816470; (1989); (A1) English View in Reaxys 3.ii : (ii) (ii) 3-(2-Aminoethyl)-N-hydroxy-1H-indole-5-carboximidamide dimaleate The product of Stage (i) (1.5 g) was taken up in 33percent ethanolic methylamine (50 ml) and after 3 h the solution was evaporated to dryness. The residue was absorbed onto silica and elution (B) gave the tryptamine as a foam (0.6 g). Patent; Glaxo Group Limited; US4833153; (1989); (A1) English View in Reaxys 9.d : (c) (d) 3-(2-Aminoethyl)-N-(phenylmethyl)-1H-indole-5-methanesulphonamide, compound with creatinine, sulphuric acid and water (1:1:1:1.2) A solution of the product of stage (c) (0.47 g) and 4-chlorobutanal dimethylacetal (0.24 g) in ethanol (50 ml) and water (10 ml) was heated at reflux for 4 h. Solvent was evaporated and the residual oil purified by column chromatography (F) which afforded the tryptamine slightly impure as an oil (0.34 g). Patent; Glaxo Group Limited; US4816470; (1989); (A1) English View in Reaxys Reductive Amination Of An Aldehyde And A Primary Amine: 4-tolualdehyde (41 mg, 0.33 mmol) and tryptamine (122 mg, 0.5 mmol) yielded 75 mg (86percent) MS (m/e): 265 (M+1) Patent; ELI LILLY AND COMPANY; EP818431; (1998); (A1) English View in Reaxys 3.ii : (ii) (ii) 3-(2-Aminoethyl)-N-hydroxy-1 H-indole-5-carboximidamide dimaleate The product of Stage (i) (1.5g) was taken up in 33percent ethanolic methylamine (50ml) and after 3h the solution was evaporated to dryness. The residue was absorbed onto silica and elution (B) gave the tryptamine as a foam (0.6g). Patent; GLAXO GROUP LIMITED; EP225726; (1991); (B1) English View in Reaxys 16 : Example 16 Example 16 5-(4,5-Dihydro-1 H-imidazol-2-yl)1 H-indole-3-ethanamine dimaleate A mixture of Intermediate 4 (1.5g), ethylene diamine (0.44g) and potassium carbonate (1.35g) in dry ethanol (75ml) was stirred under a nitrogen atmosphere for 20h. The mixture was concentrated to dryness and the residue was absorbed onto alumina. Elution (B) afforded the tryptamine as an oil. Patent; GLAXO GROUP LIMITED; EP225726; (1991); (B1) English View in Reaxys The following is a representative list of amine letters: ... 3-Isopropoxypropylamine Piperazine Thienylethylamine 3-Trifluoromethoxybenzylamine Tryptamine Tetrahydrofurfurylamine Patent; ISIS Pharmaceuticals, Inc.; US6828427; (2004); (B1) English View in Reaxys

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Among the preferred AhR ligands, mention may be made of: Flavonoids ... e. Silibinin f. Resveratrol g. Yangonin h. Indole-3-carbinol i. Tryptamine j. Kynurenine Patent; Saurat, Jean Hilaire; US2010/324109; (2010); (A1) English View in Reaxys

NH 2

Rx-ID: 13166625 View in Reaxys 2/87 Yield

Conditions & References Reaction Steps: 2 1: NH4OAc / 70 °C 2: LiAlH4 / tetrahydrofuran / Heating With lithium aluminium tetrahydride, ammonium acetate in tetrahydrofuran Gurkan, A. Selen; Karabay, Arzu; Buyukbingol, Zeliha; Adejare, Adeboye; Buyukbingol, Erdem; Archiv der Pharmazie; vol. 338; nb. 2-3; (2005); p. 67 - 73 View in Reaxys Reaction Steps: 2 1: AcOH 2: LiAH4 / tetrahydrofuran With lithium aluminium tetrahydride, acetic acid in tetrahydrofuran Harada, Hiroshi; Hirokawa, Yoshimi; Suzuki, Kenji; Hiyama, Yoichi; Oue, Mayumi; Kawashima, Hitoshi; Yoshida, Naoyuki; Furutani, Yasuji; Kato, Shiro; Bioorganic and Medicinal Chemistry Letters; vol. 13; nb. 7; (2003); p. 1301 - 1305 View in Reaxys Reaction Steps: 2 1: methylamine hydrochloride; sodium carbonate; ethanol 2: THF; diethyl ether With tetrahydrofuran, diethyl ether, ethanol, N-methylamine hydrochloride, sodium carbonate Onda et al.; Yakugaku Zasshi; vol. 76; (1956); p. 472; ; (1956); p. 13930 View in Reaxys Reaction Steps: 2 1: ammonium acetate 2: LiAlH4; diethyl ether With ammonium acetate, lithium aluminium tetrahydride, diethyl ether Young; Journal of the Chemical Society; (1958); p. 3493,3494 View in Reaxys Reaction Steps: 2 1: piperidine; acetic acid / benzene / Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / Reflux With piperidine, lithium aluminium tetrahydride, acetic acid in tetrahydrofuran, benzene Nirogi, Ramakrishna V.S.; Kambhampati, Ramasastri; Kothmirkar, Prabhakar; Konda, Jagadishbabu; Bandyala, Thrinath Reddy; Gudla, Parandhama; Arepalli, Sobhanadri; Gangadasari, Narasimhareddy P.; Shinde,

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Anil K.; Deshpande, Amol D.; Dwarampudi, Adireddy; Chindhe, Anil K.; Dubey, Pramod Kumar; Journal of Enzyme Inhibition and Medicinal Chemistry; vol. 27; nb. 3; (2012); p. 443 - 450 View in Reaxys Reaction Steps: 3 1: ammonium acetate / benzene / 12 h / |Reflux; |Inert atmosphere 2: sodium tetrahydroborate / tetrahydrofuran; methanol / 1.5 h / 20 °C / |Inert atmosphere 3: palladium 10 on activated carbon; hydrogen / methanol / 24 h / 760.05 Torr With sodium tetrahydroborate, palladium 10 on activated carbon, ammonium acetate, hydrogen in tetrahydrofuran, methanol, benzene Jin, Huijuan; Zhang, Puyong; Bijian, Krikor; Ren, Sumei; Wan, Shengbiao; Alaoui-Jamali, Moulay A.; Jiang, Tao; Marine Drugs; vol. 11; nb. 5; (2013); p. 1427 - 1439 View in Reaxys Reaction Steps: 3 1: ammonium acetate / 4 h / 105 °C 2: sodium tetrahydroborate / methanol; tetrahydrofuran / 0.5 h / 20 °C 3: hydrogen; palladium 10 on activated carbon / 12 h / 40 °C With sodium tetrahydroborate, palladium 10 on activated carbon, ammonium acetate, hydrogen in tetrahydrofuran, methanol Guo, Xiaoke; Yang, Qian; Xu, Jing; Zhang, Li; Chu, Hongxi; Yu, Peng; Zhu, Yingying; Wei, Jinglian; Chen, Weilin; Zhang, Yaozhong; Zhang, Xiaojin; Sun, Haopeng; Tang, Yiqun; You, Qidong; Bioorganic and Medicinal Chemistry; vol. 21; nb. 21; (2013); p. 6466 - 6476 View in Reaxys Reaction Steps: 2 1: ammonium acetate / 2 h / |Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / 36 h / 0 - 20 °C / |Inert atmosphere With lithium aluminium tetrahydride, ammonium acetate in tetrahydrofuran Zhao, Xiaohu; Liu, Xiaohua; Mei, Hongjiang; Guo, Jing; Lin, Lili; Feng, Xiaoming; Angewandte Chemie - International Edition; vol. 54; nb. 13; (2015); p. 4032 - 4035; Angew. Chem.; vol. 127; nb. 13; (2015); p. 4104 - 4107,4 View in Reaxys

NH 2

Rx-ID: 112864 View in Reaxys 3/87 Yield 74 %

Conditions & References With samarium diiodide, water, triethylamine in tetrahydrofuran, Time= 0.0833333h, T= 20 °C , Inert atmosphere Szostak, Michal; Sautier, Brice; Spain, Malcolm; Procter, David J.; Organic Letters; vol. 16; nb. 4; (2014); p. 1092 - 1095 View in Reaxys With lithium aluminium tetrahydride, diethyl ether Nogradi; Monatshefte fuer Chemie; vol. 88; (1957); p. 768,776 View in Reaxys Nenitzescu; Raileanu; Chemische Berichte; vol. 91; (1958); p. 1141,1143 View in Reaxys Norris; Blicke; Journal of the American Pharmaceutical Association (1912-1977); vol. 41; (1952); p. 637 View in Reaxys With methanol, ammonia, nickel, Hydrogenation Thesing; Schuelde; Chemische Berichte; vol. 85; (1952); p. 324,327 View in Reaxys With ethanol, nickel, hydrazine hydrate

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Terent'ew et al.; Khimicheskaya Nauka i Promyshlennost; vol. 4; (1959); p. 281; ; (1959); p. 21879 View in Reaxys With sodium hydroxide, hydrogen, nickel in methanol, Ambient temperature Merour, J. Y.; Buzas, A.; Synthetic Communications; vol. 18; nb. 18; (1988); p. 2331 - 2336 View in Reaxys

N O

NH 2

Rx-ID: 162529 View in Reaxys 4/87 Yield 98 %

Conditions & References With palladium 10 on activated carbon, hydrogen in methanol, Time= 24h, p= 760.051Torr Jin, Huijuan; Zhang, Puyong; Bijian, Krikor; Ren, Sumei; Wan, Shengbiao; Alaoui-Jamali, Moulay A.; Jiang, Tao; Marine Drugs; vol. 11; nb. 5; (2013); p. 1427 - 1439 View in Reaxys

94 %

With sodium hypophosphite monohydrate, 5 palladium on charcoal, hypophosphorous acid in 2-methyltetrahydrofuran, water, Time= 7h, Sonication, chemoselective reaction Baron, Marc; Metay, Estelle; Lemaire, Marc; Popowycz, Florence; Green Chemistry; vol. 15; nb. 4; (2013); p. 1006 - 1015 View in Reaxys

76 %

With hydrochlorid acid, iron in methanol, water, Time= 0.5h, Heating Pradhan, Prasun K.; Dey, Sumit; Jaisankar, Parasuraman; Giri, Venkatachalam S.; Synthetic Communications; vol. 35; nb. 7; (2005); p. 913 - 922 View in Reaxys

71.61 %

4.1.16 2-(1H-Indol-3-yl)ethanamine (7) To a solution of 3-(2-nitroethyl)-1H-indole (6, 9.12 g, 0.048 mol) in CH3OH (100mL) was added Pd/C (10percent, 1g), the mixture was stirred at 40°C with continuous H2 for 1 2h, and then was filtered and the filtrate was concentrated under reduced pressure. The residue was dissolved in water (100 mL) and extracted by EA (40 mL × 3), the organic layer was evaporated until dryness to give the compound 7 as yellow solid (5.50 g, 71.61percent). Mp= 110–112°C, lit.34 Mp= 112°C. With palladium 10 on activated carbon, hydrogen, Time= 12h, T= 40 °C Guo, Xiaoke; Yang, Qian; Xu, Jing; Zhang, Li; Chu, Hongxi; Yu, Peng; Zhu, Yingying; Wei, Jinglian; Chen, Weilin; Zhang, Yaozhong; Zhang, Xiaojin; Sun, Haopeng; Tang, Yiqun; You, Qidong; Bioorganic and Medicinal Chemistry; vol. 21; nb. 21; (2013); p. 6466 - 6476 View in Reaxys With ethanol, platinum, Hydrogenation Noland; Hartman; Journal of the American Chemical Society; vol. 76; (1954); p. 3227 View in Reaxys With ethanol, nickel, T= 100 °C , p= 77228.3Torr Lyttle; Weisblat; Journal of the American Chemical Society; vol. 77; (1955); p. 5747 View in Reaxys 5.b :Scheme 5. (b) ETOH, Raney nickel, r.t., 1h With nickel in ethanol, Time= 1h, T= 20 °C Patent; AMGEN INC.; WO2007/62175; (2007); (A2) English View in Reaxys

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E N O

NH 2

Rx-ID: 154607 View in Reaxys 5/87 Yield

Conditions & References

83.5 %

Tryptamine To the suspension of suspension of LiAlH4 (1.63 g, 43 mmol) in THF (20 mL) was added 3-(2-nitroethenyl)-1H-indole (1.62 g, 8.6 mmol) in dried tetrahydrofuran (50 mL) drop wise at 0 °C. After completion of addition, the mixture was stirred at r.t. for 6 hrs. Then it was cooled in an ice-bath, 40 mL THF/water (10 percent) were added drop wise to the cooled reaction mixture to quench unconsumed LiAlH4 until no hydrogen was liberated any more. The resulted suspension was filtered through a pad of Celite and sodium sulfate. The filtrate was concentrated in vacuo to give a yellow oily crude amine which was used without further purification (1.08 g, 83.5 percent yield). 1H NMR (400 MHz,CDCl3) δ 8.04 (s, 1H), 7.67 – 7.62 (m, 1H), 7.40 (dt, J = 8.1, 0.9 Hz, 1H), 7.23 (ddd, J = 8.2,7.1, 1.1 Hz, 1H), 7.15 (ddd, J = 8.0, 7.1, 1.1 Hz, 1H), 7.07 (d, J = 2.3 Hz, 1H), 3.07 (t, J = 6.6Hz, 2H), 2.94 (t, J = 6.6 Hz, 2H). With lithium aluminium tetrahydride in tetrahydrofuran, Time= 6h, T= 0 - 20 °C , Inert atmosphere Huan, Uozhen; Klin, Beata; Darras, Fouad H.; Heilmann, Joer; Decker, Michael; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 15 - 21 View in Reaxys With lithium aluminium tetrahydride, diethyl ether Young; Journal of the Chemical Society; (1958); p. 3493,3494 View in Reaxys With tetrahydrofuran, diethyl ether Onda et al.; Yakugaku Zasshi; vol. 76; (1956); p. 472; ; (1956); p. 13930 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, diethyl ether, Time= 3h, Heating, Yield given Ibragimov, A. A.; Yunusov, S. Yu.; Chemistry of Natural Compounds; vol. 21; nb. 4; (1985); p. 502 - 509; Khimiya Prirodnykh Soedinenii; vol. 21; nb. 4; (1985); p. 536 - 544 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran Harada, Hiroshi; Hirokawa, Yoshimi; Suzuki, Kenji; Hiyama, Yoichi; Oue, Mayumi; Kawashima, Hitoshi; Yoshida, Naoyuki; Furutani, Yasuji; Kato, Shiro; Bioorganic and Medicinal Chemistry Letters; vol. 13; nb. 7; (2003); p. 1301 - 1305 View in Reaxys Reaction Steps: 2 1: sodium tetrahydroborate / tetrahydrofuran; methanol / 1.5 h / 20 °C / |Inert atmosphere 2: palladium 10 on activated carbon; hydrogen / methanol / 24 h / 760.05 Torr With sodium tetrahydroborate, palladium 10 on activated carbon, hydrogen in tetrahydrofuran, methanol Jin, Huijuan; Zhang, Puyong; Bijian, Krikor; Ren, Sumei; Wan, Shengbiao; Alaoui-Jamali, Moulay A.; Jiang, Tao; Marine Drugs; vol. 11; nb. 5; (2013); p. 1427 - 1439 View in Reaxys

O H 2N

N H

NH 2

Rx-ID: 3830113 View in Reaxys 6/87

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Yield

Conditions & References

98 %

With pyridoxal 5'-phosphate, aromatic L-amino acid decarboxylase in various solvent(s), Time= 48h, T= 30 °C Nakazawa, Hidetsugu; Sano, Konosuke; Matsuda, Keizo; Mitsugi, Koji; Bioscience, Biotechnology, and Biochemistry; vol. 57; nb. 7; (1993); p. 1210 - 1211 View in Reaxys

92.3 %

With cyclohexenon in various solvent(s), Time= 1.5h, T= 154 °C Hashimoto, Mitsunori; Eda, Yutaka; Osanai, Yasutomo; Iwai, Toshiaki; Aoki, Seiichi; Chemistry Letters; (1986); p. 893 - 896 View in Reaxys With L-amino acid decarboxylase from Micrococcus percitreus AJ 1065, NH4OH-NH4Cl buffer, pyridoxal 5'-phosphate in water, Time= 0.5h, T= 30 °C , study of the inhibition of the enzyme by various amino acids and amines, inhibition of L-dopa in different buffer solutions, Product distribution Nakazawa, Hidetsugu; Kumagai, Hidehiko; Yamada, Hideaki; Agricultural and Biological Chemistry; vol. 51; nb. 9; (1987); p. 2531 - 2538 View in Reaxys With NH4OH-NH4Cl buffer, pyridoxal 5'-phosphate, Time= 0.5h, T= 30 °C , relative rate of CO2 evolution by aromatic L-amino acid decarboxylase from Micrococcus percitreus Nakazawa, Hidetsugu; Kumagai, Hidehiko; Yamada, Hideaki; Agricultural and Biological Chemistry; vol. 45; nb. 11; (1981); p. 2543 - 2552 View in Reaxys With isopropyl β-D-thiogalactoside, L-tryptophan decarboxylase in recombinant Escherichia coli, Time= 24h, T= 28 °C Park, Munyoung; Kang, Kiyoon; Park, Sangkyu; Back, Kyoungwhan; Bioscience, Biotechnology and Biochemistry; vol. 72; nb. 9; (2008); p. 2456 - 2458 View in Reaxys With tryptophan decarboxylase from Catharanthus roseus (Madagascar periwinkle), pyridoxal 5'-phosphate, 2-hydroxyethanethiol, T= 30 °C , pH= 8.5, aq. phosphate buffer, Enzymatic reaction, Kinetics Runguphan, Weerawat; Qu, Xudong; O'Connor, Sarah E.; Nature; vol. 468; nb. 7322; (2010); p. 461 - 467 View in Reaxys

N O

NH 2

Rx-ID: 9904880 View in Reaxys 7/87 Yield

Conditions & References With lithium aluminium tetrahydride in tetrahydrofuran, Heating Gurkan, A. Selen; Karabay, Arzu; Buyukbingol, Zeliha; Adejare, Adeboye; Buyukbingol, Erdem; Archiv der Pharmazie; vol. 338; nb. 2-3; (2005); p. 67 - 73 View in Reaxys Ates-Alagoz; Buyukbingol; Buyukbingol, Erdem; Pharmazie; vol. 60; nb. 9; (2005); p. 643 - 647 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, Reflux Nirogi, Ramakrishna V.S.; Kambhampati, Ramasastri; Kothmirkar, Prabhakar; Konda, Jagadishbabu; Bandyala, Thrinath Reddy; Gudla, Parandhama; Arepalli, Sobhanadri; Gangadasari, Narasimhareddy P.; Shinde, Anil K.; Deshpande, Amol D.; Dwarampudi, Adireddy; Chindhe, Anil K.; Dubey, Pramod Kumar; Journal of Enzyme Inhibition and Medicinal Chemistry; vol. 27; nb. 3; (2012); p. 443 - 450 View in Reaxys

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Reaction Steps: 2 1: sodium tetrahydroborate / methanol; tetrahydrofuran / 0.5 h / 20 °C 2: hydrogen; palladium 10 on activated carbon / 12 h / 40 °C With sodium tetrahydroborate, palladium 10 on activated carbon, hydrogen in tetrahydrofuran, methanol Guo, Xiaoke; Yang, Qian; Xu, Jing; Zhang, Li; Chu, Hongxi; Yu, Peng; Zhu, Yingying; Wei, Jinglian; Chen, Weilin; Zhang, Yaozhong; Zhang, Xiaojin; Sun, Haopeng; Tang, Yiqun; You, Qidong; Bioorganic and Medicinal Chemistry; vol. 21; nb. 21; (2013); p. 6466 - 6476 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, Time= 36h, T= 0 - 20 °C , Inert atmosphere Zhao, Xiaohu; Liu, Xiaohua; Mei, Hongjiang; Guo, Jing; Lin, Lili; Feng, Xiaoming; Angewandte Chemie - International Edition; vol. 54; nb. 13; (2015); p. 4032 - 4035; Angew. Chem.; vol. 127; nb. 13; (2015); p. 4104 - 4107,4 View in Reaxys

NH NH

NH 2

Rx-ID: 13166156 View in Reaxys 8/87 Yield

Conditions & References Reaction Steps: 3 1: POCl3 / 0 °C 2: NH4OAc / 70 °C 3: LiAlH4 / tetrahydrofuran / Heating With lithium aluminium tetrahydride, ammonium acetate, trichlorophosphate in tetrahydrofuran Gurkan, A. Selen; Karabay, Arzu; Buyukbingol, Zeliha; Adejare, Adeboye; Buyukbingol, Erdem; Archiv der Pharmazie; vol. 338; nb. 2-3; (2005); p. 67 - 73 View in Reaxys Reaction Steps: 3 1: phosphoryl chloride 2: methylamine hydrochloride; sodium carbonate; ethanol 3: THF; diethyl ether With tetrahydrofuran, diethyl ether, ethanol, N-methylamine hydrochloride, sodium carbonate, trichlorophosphate Onda et al.; Yakugaku Zasshi; vol. 76; (1956); p. 472; ; (1956); p. 13930 View in Reaxys Reaction Steps: 2 1: benzene 2: platinum; ethanol / Hydrogenation With ethanol, platinum, benzene Noland; Hartman; Journal of the American Chemical Society; vol. 76; (1954); p. 3227 View in Reaxys Reaction Steps: 4 1.1: trichlorophosphate / 3.5 h / 0 - 40 °C / |Inert atmosphere 1.2: 12 h / pH 8 - 9 / |Reflux 2.1: ammonium acetate / benzene / 12 h / |Reflux; |Inert atmosphere 3.1: sodium tetrahydroborate / tetrahydrofuran; methanol / 1.5 h / 20 °C / |Inert atmosphere 4.1: palladium 10 on activated carbon; hydrogen / methanol / 24 h / 760.05 Torr With sodium tetrahydroborate, palladium 10 on activated carbon, ammonium acetate, hydrogen, trichlorophosphate in tetrahydrofuran, methanol, benzene, 1.1: |Vilsmeier-Haack Formylation Jin, Huijuan; Zhang, Puyong; Bijian, Krikor; Ren, Sumei; Wan, Shengbiao; Alaoui-Jamali, Moulay A.; Jiang, Tao; Marine Drugs; vol. 11; nb. 5; (2013); p. 1427 - 1439 View in Reaxys

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Reaction Steps: 4 1: trichlorophosphate / 35 °C 2: ammonium acetate / 4 h / 105 °C 3: sodium tetrahydroborate / methanol; tetrahydrofuran / 0.5 h / 20 °C 4: hydrogen; palladium 10 on activated carbon / 12 h / 40 °C With sodium tetrahydroborate, palladium 10 on activated carbon, ammonium acetate, hydrogen, trichlorophosphate in tetrahydrofuran, methanol Guo, Xiaoke; Yang, Qian; Xu, Jing; Zhang, Li; Chu, Hongxi; Yu, Peng; Zhu, Yingying; Wei, Jinglian; Chen, Weilin; Zhang, Yaozhong; Zhang, Xiaojin; Sun, Haopeng; Tang, Yiqun; You, Qidong; Bioorganic and Medicinal Chemistry; vol. 21; nb. 21; (2013); p. 6466 - 6476 View in Reaxys

NH 2 O

NH 2

Rx-ID: 801920 View in Reaxys 9/87 Yield

Conditions & References With lithium aluminium tetrahydride Brutcher; Vanderwerff; Journal of Organic Chemistry; vol. 23; (1958); p. 146 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, Heating Wu, Tom Y. H.; Schulte, Peter G.; Organic Letters; vol. 4; nb. 23; (2002); p. 4033 - 4035 View in Reaxys

0.90 g

With lithium aluminium tetrahydride in 1,4-dioxane, Time= 34h, Heating Wang, Yu-Yun; Chen, Chinpiao; Journal of the Chinese Chemical Society; vol. 54; nb. 5; (2007); p. 1363 - 1368 View in Reaxys With lithium aluminium tetrahydride in 1,4-dioxane, Time= 50h, Heating Maresh, Justin J.; Giddings, Lesley-Ann; Friedrich, Anne; Loris, Elke A.; Panjikar, Santosh; Trout, Bernhardt L.; Stoeckigt, Joachim; Peters, Baron; O'Connor, Sarah E.; Journal of the American Chemical Society; vol. 130; nb. 2; (2008); p. 710 - 723 View in Reaxys

NH 2 O

HN H 2N

NH 2

Rx-ID: 721913 View in Reaxys 10/87 Yield

Conditions & References With zinc(II) chloride Spaeth; Lederer; Chemische Berichte; vol. 63; (1930); p. 120,123 View in Reaxys Manske; Canadian Journal of Research; vol. 5; (1931); p. 599; Chem. Zentralbl.; vol. 103; nb. I; (1932); p. 2475 View in Reaxys Schoepf; Steuer; Justus Liebigs Annalen der Chemie; vol. 558; (1947); p. 124,132 View in Reaxys

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3-<β-amino-ethyl>-indole-carboxylic acid-(2) NH 2

Rx-ID: 5427227 View in Reaxys 11/87 Yield

Conditions & References With hydrogenchloride Asahina; Fujita; Yakugaku Zasshi; nb. 476; (1921); Chem. Zentralbl.; vol. 93; nb. I; (1922); p. 357 View in Reaxys Asahina; Ohta; Yakugaku Zasshi; vol. 48; (1928); p. 53; Chem. Zentralbl.; vol. 99; nb. II; (1928); p. 58 View in Reaxys Keimatsu; Sugasawa; Kasuya; Yakugaku Zasshi; vol. 48; nb. 558; (1928); p. 108; Chem. Zentralbl.; vol. 99; nb. II; (1928); p. 1882 View in Reaxys

isoevodiamine

NH 2

Rx-ID: 5497286 View in Reaxys 12/87 Yield

Conditions & References With potassium hydroxide Asahina; Ohta; Chemische Berichte; vol. 61; (1928); p. 321 View in Reaxys Asahina; Acta Phytochimica; vol. 1; (1922); p. 81; Chem. Zentralbl.; vol. 94; nb. III; (1923); p. 248 View in Reaxys Asahina; Fujita; Yakugaku Zasshi; nb. 476; (1921); Chem. Zentralbl.; vol. 93; nb. I; (1922); p. 357 View in Reaxys

O O

NH 2

Rx-ID: 27988328 View in Reaxys 13/87 Yield 88 %

Conditions & References in various solvent(s), Time= 1h, T= 150 °C , microwave irradiation Choy, Jason; Jaime-Figueroa, Saul; Jiang, Laurence; Wagner, Paul; Synthetic Communications; vol. 38; nb. 21; (2008); p. 3840 - 3853 View in Reaxys

88 %

4 :EXAMPLE 4; To extend the synthetic potential of this deprotection method, this protocol was further expanded to a wide range of N-Boc amines in HFIP. In each case (except as otherwise noted), 1 mmol of protected compound was microwave heated at 150° C. in HFIP (5 mL) for the time shown, and the deprotected compound recovered by chromatography. The results are shown in Table 4. In all cases, the deprotection product was obtained in good to excellent yields. With hexafluoroisopropyl alcohol, Time= 1h, T= 150 °C , Microwave irradiation Patent; Roch Palo Alto LLC; US2009/203910; (2009); (A1) English View in Reaxys

88 %

4 :Example 4; To extend the synthetic potential of this deprotection method, this protocol was further expanded to a wide range of N-Boc amines in HFIP. In each case (except as otherwise noted), 1 mmol of protected compound was

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microwave heated at 150°C in HFIP (5 mL) for the time shown, and the deprotected compound recovered by chromatography. The results are shown in Table 4. In all cases, the deprotection product was obtained in good to excellent yields. With hexafluoroisopropyl alcohol, Time= 1h, T= 150 °C , Microwave irradiation Patent; F. Hoffmann-La Roche AG; EP2070899; (2009); (A1) English View in Reaxys

NH 2 NH 2

Rx-ID: 142302 View in Reaxys 14/87 Yield

Conditions & References With lithium aluminium tetrahydride Groves; Swan; Journal of the Chemical Society; (1952); p. 650,658 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, Time= 3h, T= 20 °C , Inert atmosphere Fantacuzzi, Marialuigia; Maccallini, Cristina; Di Matteo, Mauro; Ammazzalorso, Alessandra; Bruno, Isabella; De Filippis, Barbara; Giampietro, Letizia; Mollica, Adriano; Amoroso, Rosa; Journal of Pharmaceutical and Biomedical Analysis; vol. 120; (2016); p. 419 - 424 View in Reaxys

NH NH 2

NH 2

Rx-ID: 3829957 View in Reaxys 15/87 Yield 63 %

Conditions & References in diphenylether, Time= 10h, Heating Biswas, Kshetra M.; Jackson, Anthony H.; Kobaisy, Mozaina M.; Shannon, Patrick V. R.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); nb. 4; (1992); p. 461 - 468 View in Reaxys 5.4 Kinetic analysis General procedure: Reaction mixtures of 50μl assays containing recombinant protein (25μg for P. somniferum TyDC 5-hydroxytryptophan, 3μg for the P. somniferum TyDC dopa, 25μg for C. roseus TDC dopa and 3μg for the C. roseus TDC tryptophan) and varying concentration of substrate (0.05–20mM of 5-hydroxytryptophan, 0.005–5mM of tryptophan and 0.05–15mM of dopa) were prepared in 50mM phosphate buffer (pH 7.5) and incubated at 25°C. An equal volume of 0.8M HCO2H was added to each reaction mixture (15min for P. somniferum TyDC 5-hydroxytryptophan assays, 2.5min for P. somniferum dopa assays, 15min for C. roseus TDC dopa assays and 2.5min for C. roseus tryptophan assays) with supernatants individually was subjected to HPLC-electrochemical analysis. Kinetic data points were performed in triplicate and kinetic values were evaluated by hyperbolic regression. An isocratic running buffer consisting of 50mM phosphate buffer pH 4.3, 25percent acetonitrile, and 0.5mM octyl sulfate was used for the 5hydroxytryptophan characterization, whereas an isocratic running buffer consisting of 50mM phosphate buffer pH 4.3, 15percent acetonitrile, and 0.5mM octyl sulfate was used for the dopa characterization. The amounts of products in reaction mixtures containing different concentrations of substrate were quantified based on a standard curve generated using authentic standards at identical conditions of HPLC-electrochemical analysis. With Catharanthus roseus tryptophan decarboxylase in aq. phosphate buffer, T= 25 °C , pH= 7.5, Enzymatic reaction, Kinetics, Reagent/catalyst Torrens-Spence, Michael P.; Lazear, Michael; Von Guggenberg, Renee; Ding, Haizhen; Li, Jianyong; Phytochemistry; vol. 106; (2014); p. 37 - 43

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View in Reaxys

NH NH 2

NH 2

Rx-ID: 3829960 View in Reaxys 16/87 Yield

Conditions & References

90 %

With hydrogenchloride in various solvent(s), Time= 0.333333h, Heating Ibragimov, A. A.; Yunusov, S. Yu.; Chemistry of Natural Compounds; vol. 21; nb. 4; (1985); p. 502 - 509; Khimiya Prirodnykh Soedinenii; vol. 21; nb. 4; (1985); p. 536 - 544 View in Reaxys

72 %

With hydrogenchloride in various solvent(s), Time= 0.333333h, Heating Tulyaganov, T. S.; Ibragimov, A. A.; Yunusov, S. Yu.; Chemistry of Natural Compounds; vol. 17; (1981); p. 149 152; Khimiya Prirodnykh Soedinenii; vol. 17; nb. 2; (1981); p. 192 - 195 View in Reaxys

O O

NH 2

Rx-ID: 11321733 View in Reaxys 17/87 Yield

Conditions & References Reaction Steps: 2 1: NH3 / CH2Cl2 / 0.5 h 2: 0.90 g / LiAlH4 / dioxane / 34 h / Heating With lithium aluminium tetrahydride, ammonia in 1,4-dioxane, dichloromethane Wang, Yu-Yun; Chen, Chinpiao; Journal of the Chinese Chemical Society; vol. 54; nb. 5; (2007); p. 1363 - 1368 View in Reaxys Reaction Steps: 2 1: NH3 / dioxane 2: lithium aluminum hydride / tetrahydrofuran / Heating With lithium aluminium tetrahydride, ammonia in tetrahydrofuran, 1,4-dioxane Wu, Tom Y. H.; Schulte, Peter G.; Organic Letters; vol. 4; nb. 23; (2002); p. 4033 - 4035 View in Reaxys

NH NH

thiophene-2-methyl halide NH 2

Rx-ID: 14336060 View in Reaxys 18/87 Yield

Conditions & References Reaction Steps: 3 1: POCl3 2: AcOH 3: LiAH4 / tetrahydrofuran With lithium aluminium tetrahydride, acetic acid, trichlorophosphate in tetrahydrofuran, 1: Vilsmeier reaction Harada, Hiroshi; Hirokawa, Yoshimi; Suzuki, Kenji; Hiyama, Yoichi; Oue, Mayumi; Kawashima, Hitoshi; Yoshida, Naoyuki; Furutani, Yasuji; Kato, Shiro; Bioorganic and Medicinal Chemistry Letters; vol. 13; nb. 7; (2003); p. 1301 - 1305

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View in Reaxys Reaction Steps: 3 1: diethyl ether / Heating 2: NH3 / dioxane 3: lithium aluminum hydride / tetrahydrofuran / Heating With lithium aluminium tetrahydride, ammonia in tetrahydrofuran, 1,4-dioxane, diethyl ether Wu, Tom Y. H.; Schulte, Peter G.; Organic Letters; vol. 4; nb. 23; (2002); p. 4033 - 4035 View in Reaxys

N O NH 2

NH 2

Rx-ID: 28153758 View in Reaxys 19/87 Yield

Conditions & References

98 %

Stage 1: With trifluoroacetic acid in dichloromethane, T= 0 - 25 °C , Inert atmosphere Stage 2: With sodium hydrogencarbonate in water, pH= > 7, Inert atmosphere, Saturated solution Nicolaou; Krasovskiy, Arkady; Trepanier, Vincent E.; Chen, David Y.-K.; Angewandte Chemie - International Edition; vol. 47; nb. 22; (2008); p. 4217 - 4220 View in Reaxys

98 %

With trifluoroacetic acid in dichloromethane, Time= 2h, T= 0 - 25 °C , Inert atmosphere Nicolaou, K. C.; Krasovskiy, Arkady; Majumder, Utpal; Trepanier, Vincent E.; Chen, David Y.-K.; Journal of the American Chemical Society; vol. 131; (2009); p. 3690 - 3699 View in Reaxys

NH 2

Rx-ID: 112865 View in Reaxys 20/87 Yield

Conditions & References With ammonia, nickel, T= 100 °C , p= 66195.7Torr , Hydrogenation Thesing; Schuelde; Chemische Berichte; vol. 85; (1952); p. 324,327 View in Reaxys

NH 2

Rx-ID: 113811 View in Reaxys 21/87 Yield

Conditions & References With ammonia, water Hoshino; Shimodaira; Justus Liebigs Annalen der Chemie; vol. 520; (1935); p. 19,26 View in Reaxys

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NH Cl

E N O

NH 2

Rx-ID: 1811313 View in Reaxys 22/87 Yield

Conditions & References

81 %

With hydrogenchloride, lithium aluminium tetrahydride in tetrahydrofuran, diethyl ether, Time= 3h, Heating Tulyaganov, T. S.; Ibragimov, A. A.; Yunusov, S. Yu.; Chemistry of Natural Compounds; vol. 17; (1981); p. 149 152; Khimiya Prirodnykh Soedinenii; vol. 17; nb. 2; (1981); p. 192 - 195 View in Reaxys

NH O

NH 2

Rx-ID: 2121986 View in Reaxys 23/87 Yield

Conditions & References

82 %

With sodium hydroxide in water, ethylene glycol Shono, Tatsuya; Matsumura, Yoshihiro; Kanazawa, Takenobu; Tetrahedron Letters; vol. 24; nb. 12; (1983); p. 1259 - 1262 View in Reaxys

NH H

NH 2

(-)-enantiomer

L-isomer

Rx-ID: 2584317 View in Reaxys 24/87 Yield

Conditions & References With hydrogenchloride, Time= 24h, Heating Kirkup, Michael P.; Moore, Richard E.; Tetrahedron Letters; vol. 24; nb. 20; (1983); p. 2087 - 2090 View in Reaxys

NH O HN

H N

NH 2

S O

Rx-ID: 2628029 View in Reaxys 25/87 Yield 78 %

Conditions & References With borane-ammonia in ethanol, Irradiation Hamada, Tatsuo; Nishida, Atsushi; Yonemitsu, Osamu; Tetrahedron Letters; vol. 30; nb. 32; (1989); p. 4241 4244

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View in Reaxys

HN O

E O

NH 2 O OH

Rx-ID: 2671471 View in Reaxys 26/87 Yield

Conditions & References in sodium hydroxide Sato, Hiroji; Kawagishi, Hirokazu; Nishimura, Tsutomu; Yoneyama, Syozou; Yoshimoto, Yuko; et al.; Agricultural and Biological Chemistry; vol. 49; nb. 10; (1985); p. 2969 - 2974 View in Reaxys O O

NH 2

Rx-ID: 3094910 View in Reaxys 27/87 Yield

Conditions & References With sodium hydroxide, Time= 2h, Heating, Yield given Nagarathnam, Dhanapalan; Journal of Heterocyclic Chemistry; vol. 29; nb. 4; (1992); p. 953 - 958 View in Reaxys

NH NH

NH 2

Rx-ID: 3119499 View in Reaxys 28/87 Yield

Conditions & References

52 %

With hydrogen, rhenium, nickel in methanol, Time= 12h, p= 760Torr , Ambient temperature Severin, Theodor; Lerche, Holger; Mayring, Lothar; Chemische Berichte; vol. 113; nb. 3; (1980); p. 970 - 978 View in Reaxys

HN E

NH 2

Rx-ID: 3698370 View in Reaxys 29/87 Yield

Conditions & References in sodium hydroxide

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Sato, Hiroji; Kawagishi, Hirokazu; Nishimura, Tsutomu; Yoneyama, Syozou; Yoshimoto, Yuko; et al.; Agricultural and Biological Chemistry; vol. 49; nb. 10; (1985); p. 2969 - 2974 View in Reaxys

NH 2

Rx-ID: 4075841 View in Reaxys 30/87 Yield

Conditions & References With hydrogenchloride, Time= 2h, Heating Guengoer, Timur; Malabre, Patrice; Teulon, Jean-Marie; Camborde, Francoise; Meignen, Joelle; et al.; Journal of Medicinal Chemistry; vol. 37; nb. 25; (1994); p. 4307 - 4316 View in Reaxys

H N HN

NH 2

Rx-ID: 4151994 View in Reaxys 31/87 Yield

Conditions & References

31 %, 38 %

With hydrogen, palladium on activated charcoal in methanol, Time= 96h Diker, Khalid; Tetrahedron Letters; vol. 36; nb. 14; (1995); p. 2497 - 2500 View in Reaxys

NH 2

NH NH

O S

O OH

NH S

S S

Rx-ID: 4842021 View in Reaxys 32/87 Yield

Conditions & References With Phoma lingam, metabolic pathway leading to the fungal detoxification of the title compound Pedras, M. Soledade C.; Okanga, Francis I.; Journal of Organic Chemistry; vol. 63; nb. 3; (1998); p. 416 - 417 View in Reaxys

(+-)-hydroxy-indol-3-yl-acetic acid amide NH 2

Rx-ID: 5427226 View in Reaxys 33/87 Yield

Conditions & References With lithium aluminium tetrahydride Brutcher; Vanderwerff; Journal of Organic Chemistry; vol. 23; (1958); p. 146 View in Reaxys

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indolyl-(3)-acetonitrile NH 2

Rx-ID: 5427228 View in Reaxys 34/87 Yield

Conditions & References With ethanol, sodium Majima; Hoshino; Chemische Berichte; vol. 58; (1925); p. 2045 View in Reaxys

N-<β-indolyl-(3)-ethyl>-phthalimide NH 2

Rx-ID: 5427229 View in Reaxys 35/87 Yield

Conditions & References With hydrazine hydrate Manske; Journal of the American Chemical Society; vol. 51; (1929); p. 1203; Canadian Journal of Research; vol. 4; (1931); p. 594; Chem. Zentralbl.; vol. 102; nb. II; (1931); p. 2738 View in Reaxys

NH 2

O HO

H 2N

O HO

NH 2

OH O

NH 2

Rx-ID: 5701012 View in Reaxys 36/87 Yield

Conditions & References Akabori; Narita; Proceedings of the Japan Academy; vol. 25; nb. 11; (1949); p. 6 View in Reaxys

NH Cl N

NH 2

Rx-ID: 9643227 View in Reaxys 37/87 Yield 94 %

Conditions & References With thiamine diphosphate in methanol, Time= 1h, T= 80 °C Pal, Bikash; Jaisankar, Parasuraman; Giri, Venkatachalam S.; Synthetic Communications; vol. 34; nb. 7; (2004); p. 1317 - 1323 View in Reaxys

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NH NH HO

NH 2

Rx-ID: 9719004 View in Reaxys 38/87 Yield

Conditions & References

81 %

Stage 1: With triphenyl phosphite, chlorine, triethylamine in dichloromethane, T= -30 °C Stage 2: in dichloromethane, T= -30 - 20 °C Stage 3: With water Spaggiari, Alberto; Blaszczak, Larry C.; Prati, Fabio; Organic Letters; vol. 6; nb. 22; (2004); p. 3885 - 3888 View in Reaxys

NH O Z

NH 2

Rx-ID: 9813406 View in Reaxys 39/87 Yield

Conditions & References

71 %

With hydrogenchloride, iron in methanol, water, Time= 0.5h, Heating Pradhan, Prasun K.; Dey, Sumit; Jaisankar, Parasuraman; Giri, Venkatachalam S.; Synthetic Communications; vol. 35; nb. 7; (2005); p. 913 - 922 View in Reaxys

NH NH

(+-)-2-butyl-octan-1-ol NH 2

Rx-ID: 11300935 View in Reaxys 40/87 Yield

Conditions & References Reaction Steps: 3 1: diethyl ether / 4 h / 0 - 20 °C 2: NH3 / CH2Cl2 / 0.5 h 3: 0.90 g / LiAlH4 / dioxane / 34 h / Heating With lithium aluminium tetrahydride, ammonia in 1,4-dioxane, diethyl ether, dichloromethane Wang, Yu-Yun; Chen, Chinpiao; Journal of the Chinese Chemical Society; vol. 54; nb. 5; (2007); p. 1363 - 1368 View in Reaxys

H N

NH 2

Rx-ID: 18095841 View in Reaxys 41/87 Yield

Conditions & References Reaction Steps: 2 1: KOH / ethanol / 6 h / Heating 2: 10percent aq. HCl / 2 h / Heating With hydrogenchloride, potassium hydroxide in ethanol Guengoer, Timur; Malabre, Patrice; Teulon, Jean-Marie; Camborde, Francoise; Meignen, Joelle; et al.; Journal of Medicinal Chemistry; vol. 37; nb. 25; (1994); p. 4307 - 4316 View in Reaxys

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N E

O NH 2

Rx-ID: 18095907 View in Reaxys 42/87 Yield

Conditions & References Reaction Steps: 3 1: 90percent aq. HCOOH / 1 h / Heating 2: KOH / ethanol / 6 h / Heating 3: 10percent aq. HCl / 2 h / Heating With hydrogenchloride, potassium hydroxide, formic acid in ethanol Guengoer, Timur; Malabre, Patrice; Teulon, Jean-Marie; Camborde, Francoise; Meignen, Joelle; et al.; Journal of Medicinal Chemistry; vol. 37; nb. 25; (1994); p. 4307 - 4316 View in Reaxys

O N

NH 2

Rx-ID: 18273152 View in Reaxys 43/87 Yield

Conditions & References Reaction Steps: 2 1: 38 percent / t-BuOK / 1,2-dimethoxy-ethane 2: NaOH, H2, Raney-Ni / methanol / Ambient temperature With sodium hydroxide, potassium tert-butylate, hydrogen, nickel in methanol, ethylene glycol dimethyl ether Merour, J. Y.; Buzas, A.; Synthetic Communications; vol. 18; nb. 18; (1988); p. 2331 - 2336 View in Reaxys

NH NH

Raney nickel

dicobalthexacarbonyl propargylium tetrafluoroborate NH 2

Rx-ID: 19879512 View in Reaxys 44/87 Yield

Conditions & References Reaction Steps: 3 1: 59 percent / 1) POCl3 ; 2) CaCO3; / 1) 25 deg C; 30 min. 2) 48-50 deg C; 30 min. 2: 53 percent / CH3NH2*HCl; Na2CO3 / ethanol / 168 h / Ambient temperature 3: LiAlH4 / diethyl ether; tetrahydrofuran / 3 h / Heating With lithium aluminium tetrahydride, N-methylamine hydrochloride, sodium carbonate, calcium carbonate, trichlorophosphate in tetrahydrofuran, diethyl ether, ethanol Ibragimov, A. A.; Yunusov, S. Yu.; Chemistry of Natural Compounds; vol. 21; nb. 4; (1985); p. 502 - 509; Khimiya Prirodnykh Soedinenii; vol. 21; nb. 4; (1985); p. 536 - 544 View in Reaxys

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NH NH

Raney nickel

3-<3,4-dimethoxy-phenyl>-2,3-epoxy-propionic acid

NH 2

Rx-ID: 19879516 View in Reaxys 45/87 Yield

Conditions & References Reaction Steps: 3 1: 1) POCl3; 2) CaCO3; 3) CH3COONa, Na2CO3; / 1) 100 deg C; 2) 25 deg C, 30 min. 3) 55-60 deg C; 30 min. 4) water, reflux, 3 h. 2: 45 percent / methylamine hydrochloride; Na2CO3; / 144 h 3: 81 percent / 1) LIAlH4; 2) HCl g / tetrahydrofuran; diethyl ether / 3 h / Heating With hydrogenchloride, lithium aluminium tetrahydride, N-methylamine hydrochloride, sodium acetate, sodium carbonate, calcium carbonate, trichlorophosphate in tetrahydrofuran, diethyl ether Tulyaganov, T. S.; Ibragimov, A. A.; Yunusov, S. Yu.; Chemistry of Natural Compounds; vol. 17; (1981); p. 149 152; Khimiya Prirodnykh Soedinenii; vol. 17; nb. 2; (1981); p. 192 - 195 View in Reaxys

dicobalthexacarbonyl propargylium tetrafluoroborate O

NH 2

Rx-ID: 19879844 View in Reaxys 46/87 Yield

Conditions & References Reaction Steps: 2 1: 53 percent / CH3NH2*HCl; Na2CO3 / ethanol / 168 h / Ambient temperature 2: LiAlH4 / diethyl ether; tetrahydrofuran / 3 h / Heating With lithium aluminium tetrahydride, N-methylamine hydrochloride, sodium carbonate in tetrahydrofuran, diethyl ether, ethanol Ibragimov, A. A.; Yunusov, S. Yu.; Chemistry of Natural Compounds; vol. 21; nb. 4; (1985); p. 502 - 509; Khimiya Prirodnykh Soedinenii; vol. 21; nb. 4; (1985); p. 536 - 544 View in Reaxys

Cl O

3-<3,4-dimethoxy-phenyl>-2,3-epoxy-propionic acid

NH 2

Rx-ID: 19879847 View in Reaxys 47/87 Yield

Conditions & References Reaction Steps: 2 1: 45 percent / methylamine hydrochloride; Na2CO3; / 144 h 2: 81 percent / 1) LIAlH4; 2) HCl g / tetrahydrofuran; diethyl ether / 3 h / Heating With hydrogenchloride, lithium aluminium tetrahydride, N-methylamine hydrochloride, sodium carbonate in tetrahydrofuran, diethyl ether Tulyaganov, T. S.; Ibragimov, A. A.; Yunusov, S. Yu.; Chemistry of Natural Compounds; vol. 17; (1981); p. 149 152; Khimiya Prirodnykh Soedinenii; vol. 17; nb. 2; (1981); p. 192 - 195 View in Reaxys

nickel

dicobalthexacarbonyl propargylium tetrafluoroborate NH 2

Rx-ID: 20294356 View in Reaxys 48/87

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Yield

Conditions & References Reaction Steps: 5 1: 1.) dimsyl sodium 2: 96 percent / NBS, benzoyl peroxide / CCl4 / 6 h / Heating 3: 96 percent / tetrahydrofuran; dimethylsulfoxide / 12 h / Ambient temperature 4: H2 / Raney nickel / ethanol / 2 h / 1810.02 Torr 5: aq. NaOH / 2 h / Heating With sodium hydroxide, N-bromosuccinmide, meta-chloroperoxybenzoic acid, hydrogen, sodium methylsulfinylmethanide, nickel in tetrahydrofuran, tetrachloromethane, ethanol, dimethyl sulfoxide Nagarathnam, Dhanapalan; Journal of Heterocyclic Chemistry; vol. 29; nb. 4; (1992); p. 953 - 958 View in Reaxys O O

S N

dicobalthexacarbonyl propargylium tetrafluoroborate NH 2

Rx-ID: 20295685 View in Reaxys 49/87 Yield

Conditions & References Reaction Steps: 4 1: 96 percent / NBS, benzoyl peroxide / CCl4 / 6 h / Heating 2: 96 percent / tetrahydrofuran; dimethylsulfoxide / 12 h / Ambient temperature 3: H2 / Raney nickel / ethanol / 2 h / 1810.02 Torr 4: aq. NaOH / 2 h / Heating With sodium hydroxide, N-bromosuccinmide, meta-chloroperoxybenzoic acid, hydrogen, nickel in tetrahydrofuran, tetrachloromethane, ethanol, dimethyl sulfoxide Nagarathnam, Dhanapalan; Journal of Heterocyclic Chemistry; vol. 29; nb. 4; (1992); p. 953 - 958 View in Reaxys O O

S N

dicobalthexacarbonyl propargylium tetrafluoroborate NH 2

Rx-ID: 20295707 View in Reaxys 50/87 Yield

Conditions & References Reaction Steps: 3 1: 96 percent / tetrahydrofuran; dimethylsulfoxide / 12 h / Ambient temperature 2: H2 / Raney nickel / ethanol / 2 h / 1810.02 Torr 3: aq. NaOH / 2 h / Heating With sodium hydroxide, hydrogen, nickel in tetrahydrofuran, ethanol, dimethyl sulfoxide Nagarathnam, Dhanapalan; Journal of Heterocyclic Chemistry; vol. 29; nb. 4; (1992); p. 953 - 958 View in Reaxys O O

dicobalthexacarbonyl propargylium tetrafluoroborate N

NH 2

Rx-ID: 20329465 View in Reaxys 51/87 Yield

Conditions & References Reaction Steps: 2 1: H2 / Raney nickel / ethanol / 2 h / 1810.02 Torr 2: aq. NaOH / 2 h / Heating With sodium hydroxide, hydrogen, nickel in ethanol

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Nagarathnam, Dhanapalan; Journal of Heterocyclic Chemistry; vol. 29; nb. 4; (1992); p. 953 - 958 View in Reaxys

Z O HN

N H

N OH

NH 2 L-isomer

Rx-ID: 21623777 View in Reaxys 52/87 Yield

Conditions & References Reaction Steps: 2 1: Hydrogen / 30percent Pd/C / methanol / 24 h 2: 6N HCl / 24 h / Heating With hydrogenchloride, hydrogen, palladium on activated charcoal in methanol Kirkup, Michael P.; Moore, Richard E.; Tetrahedron Letters; vol. 24; nb. 20; (1983); p. 2087 - 2090 View in Reaxys

NH 2

Rx-ID: 22170179 View in Reaxys 53/87 Yield

Conditions & References Reaction Steps: 2 1: diethyl ether; phosphorus (III)-bromide 2: water; NH3 With diethyl ether, ammonia, water, phosphorus tribromide Hoshino; Shimodaira; Justus Liebigs Annalen der Chemie; vol. 520; (1935); p. 19,26 View in Reaxys

NH O–

O S

N+

NH 2

Rx-ID: 22198387 View in Reaxys 54/87 Yield

Conditions & References Reaction Steps: 2 1: H2O 2: Raney nickel; NH3; methanol / Hydrogenation With methanol, ammonia, water, nickel Thesing; Schuelde; Chemische Berichte; vol. 85; (1952); p. 324,327 View in Reaxys Reaction Steps: 2 1: H2O 2: Raney nickel; methanol. NH3 / 100 °C / 66195.7 Torr / Hydrogenation With ammonia, water, nickel Thesing; Schuelde; Chemische Berichte; vol. 85; (1952); p. 324,327 View in Reaxys

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NH O

O O

NH 2

Rx-ID: 22224050 View in Reaxys 55/87 Yield

Conditions & References Reaction Steps: 2 1: aq.-ethanolic NaOH-solution; aqueous hydrochloric acid 2: Raney nickel; ethanol / 100 °C / 77228.3 Torr With hydrogenchloride, sodium hydroxide, ethanol, nickel Lyttle; Weisblat; Journal of the American Chemical Society; vol. 77; (1955); p. 5747 View in Reaxys

NH O O

NH 2

Rx-ID: 22287523 View in Reaxys 56/87 Yield

Conditions & References Reaction Steps: 2 1: diethyl ether; aqueous NH3 2: LiAlH4 With ammonium hydroxide, lithium aluminium tetrahydride, diethyl ether Groves; Swan; Journal of the Chemical Society; (1952); p. 650,658 View in Reaxys

HO O

O O

OH NH 2

Rx-ID: 23920560 View in Reaxys 57/87 Yield

Conditions & References 11 : EXAMPLE 11 EXAMPLE 11 In a 100L round-bottom flask, the amide solution (11) in IPAC (50L) was solvent switched to ethanol under vacuum below 35° C. Dodecanethiol (8.04 kg) was added followed by lithium hydroxide monohydrate (1.67 kg). The batch was heated to about 50° C. for about an hour and then cooled to room temperature. The batch was concentrated to about 40L and toluene (25L) was added followed by aqueous citric acid (2M, 30L). The toluene layer was removed and additional toluene (25L) was added followed by ethanol (4L). The toluene layer was removed and additional toluene (30L) was added followed by pH adjustment with 50percent NaOH (about 8-9L). The batch was heated to about 50° C. Water (10L) was added and the aqueous layer was removed. The primary amine product (12) was used to prepare the final compound (13). With sodium hydroxide, lithium hydroxide monohydrate in ethanol, water, toluene Patent; Chung, John Y. L.; Farr, Roger N.; Humphrey, Guy R.; US2003/13876; (2003); (A1) English View in Reaxys

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Br O N

NH 2

Rx-ID: 24587507 View in Reaxys 58/87 Yield

Conditions & References Compound 4l was formed by reducing the nitrile 5d with AlH3 and acylating the resulting crude tryptamine 5e with Ac2 O. All new compounds were analyzed for C, H, N and the analytical results were within +-0.4percent of the theoretical values. 1 H NMR and IR data of the new compounds were found in accord with the assigned structures (see below). The routes of preparation are illustrated by Scheme I, Scheme II, Scheme III and Scheme IV hereinbelow. Table I and Table II summarize the chemical-physical data of some of the intermediates. Melting points were determined on a Buchi apparatus in glass capillary tubes and are uncorrected. 1 H NMR spectra were recorded on a Bruker 200 or a Varian EM 360 L spectrometers; chemical shifts are reported in parts per million (ppm, δ) using chloroform or tetramethylsilane as internal standards, and signals are quoted as s (singlet), d (doublet), t (triplet), q (quartet), br s (broad singlet) or m (multiplet). IR spectra were determined with a Perkin-Elmer 257 spectrophotometer; values are reported in reciprocal centimeters (cm-1). Patent; Instituto Farmacologico Lombardo-IFLO, S.a.S.; US5552428; (1996); (A1) English View in Reaxys

Br HN

AlH3 (ref)

OH HO

S OO

NH 2

Rx-ID: 24587508 View in Reaxys 59/87 Yield

Conditions & References 2-Iodo-N-cyclopropanoyl-5-methoxytryptamine (4m). 2,6-Dibromomelatonin (4l). A solution of 5d (1.725 g, 5 mmol) in THF (10 mL) was added dropwise to a solution of AlH3 (ref) (from 0.96 mL of 100percent H2 SO4 and 37 mmol of LiAlH4 in 50 mL of THF). The mixture was stirred for 1 hour at room temperature, then the excess of hydride was destroyed by addition of ice. The supernatant was decanted and the aluminium salts were treated with cold 25 percent NaOH, and the aqueous solution was extracted with CH2 Cl2. The extracts were collected together with the THF solution, washed with brine, dried (Na2 SO4) and concentrated in vacuo, to give the crude tryptamine 5e, in the form of oil. With sodium hydroxide, LiAlH4 in tetrahydrofuran Patent; Instituto Farmacologico Lombardo-IFLO, S.a.S.; US5552428; (1996); (A1) English View in Reaxys

3-[2-(Ethylamino)ethyl]-N-methyl-1H-indole-5-ethaneasulphonamide hemisuccinate hemihydrate NH 2

Rx-ID: 24835943 View in Reaxys 60/87 Yield

Conditions & References 10 : Method (I) To this was added the product of Preparation 5 (8 g) in ethanolic dimethylamine (33percent w/v, 400 ml) and the resulting suspension stirred for 18 h at 20° under an atmosphere of hydrogen. The suspension was filtered through hyflo and evaporated to give an oil (8.4 g) which was purified by flash chromatography (8 cm dia. col.) to give the tryptamine as an oil (6.0 g).

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The oil was extracted with diethyl ether (2 l) and ethyl acetate (200 ml) to leave a residue (0.5 g) which was discarded. The organic extracts were combined, evaporated in vacuo and dissolved in analar ethyl acetate (300 ml). Patent; Glaxo Group Limited; US4994483; (1991); (A1) English View in Reaxys

HN HN S O O

NH 2

H 2N

Rx-ID: 24842038 View in Reaxys 61/87 Yield

Conditions & References 4.iv : (iv) The cooled mixture was evaporated to dryness and the residue chromatographed twice (A) to give the tryptamine as an oil (70 mg) which was dissolved in a boiling mixture of ethanol (5.6 ml) and water (0.7 ml) and treated with an aqueous solution of creatinine and sulphuric acid (1:1, 2M, 0.1 ml). On cooling the title compound was deposited as a solid (96 mg) m.p. 217°-220° (softens at 210°). Analysis Found: C,47.0;H,5.9;N,14.2. C19 H23 N3 O2 S.C4 H7 N3 O.H2 SO4.H2 O requires C,47.1;H,5.8;N,14.3percent. Patent; Glaxo Group Limited; US4994483; (1991); (A1) English View in Reaxys

HN N S O

NH 2

H 2N

Rx-ID: 24842046 View in Reaxys 62/87 Yield

Conditions & References 8.v : (v) The combined extracts were dried (Na2 SO4) and evaporated in vacuo to give the tryptamine as an oil (0.05 g) which was dissolved in a hot mixture of ethanol (9 ml) and water (1 ml), and a solution of creatinine in sulphuric acid (2M, 1:1 0.08 ml) added. Filtration of the cooled mixture gave the title compound as a solid (0.05 g) m.p. 223°-225° (dec.). Analysis Found: C,39.9;H,6.2;N,15.85. C14 H21 N3 O2 S.C4 H7 N3 O.H2 SO4.2H 2 O requires C,39.9;H,6.3;N,15.5percent. Patent; Glaxo Group Limited; US4994483; (1991); (A1) English View in Reaxys H 2N

HO HN

Cl Cl

H 2N O

NH 2

Rx-ID: 24978233 View in Reaxys 63/87 Yield

Conditions & References 1 : Preparation of N-acetyl-5-methoxy-6,7-dichlorotryptamine(6,7-dichloromelatonin) The indolecarboxylic acid from the previous preparation was decarboxylated by heating with 140 ml of 3N aqueous hydrochloric acid under vigorous reflux for about 48 hours. The starting carboxylic acid was insoluble in the aqueous acidic mixture but the product of the decarboxylation 6methoxy-7,8-dichlorotryptamine was soluble therein. Upon cooling the reaction mixture, a portion of the hydrochloride salt of the tryptamine precipitated. Water was added to redissolve the salt. The solution was filtered to remove a small quantity of an insoluble impurity.

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The pH of the acidic aqueous filtrate was adjusted to about pH=12 with concentrated aqueous sodium hydroxide. A product, comprising 5-methoxy-6,7-dichlorotryptamine, precipitated. The mixture was refrigerated. The product was isolated by filtration from the chilled reaction mixture. 3.31 g of a grayish powder melting at about 181°-184° C. were obtained. Recrystallization of a portion of this precipitate from aqueous ethanol yielded grayish brown platelets of 5-methoxy-6,7-dichlorotryptamine melting at about 189°-192° C. Analysis Calc.: C, 50.99; H, 4.67; N, 10.81; Cl, 27.36; Found: C, 51.08; H, 4.73; N, 11.05; Cl, 27.16. NMR (acetone-d6 /DMSO-d6) δ at 1.70 (br s, 1H, N--H); 1.90 (br s, 1H, N--H); 2.96 (t, J=10Hz, 2H, β-CH2); 3.49 (t, J=10 Hz, α-CH2); 3.91 (s, 3H, OCH3); 7.20 (s, 1H, 2-H); 7.27 (s, 1H 4-H). With hydrogenchloride Patent; Eli Lilly and Company; US4614807; (1986); (A1) English View in Reaxys

NH 2

O S HN

H 2N

Rx-ID: 25139378 View in Reaxys 64/87 Yield

Conditions & References 11.d : T.l.c. (d) 3-(2-Aminomethyl)-N-cyclohexyl-1H-indole-5-methanesulphonamide, compound with creatinine, sulphuric acid, and water (1:1:1:1) By a procedure similar to that described in example 9(d) the product of stage (c) (0.19 g) was condensed with 4chlorobutanal dimethyl acetal (0.09 g) and flash chromatographed (Kieselgel 9385) (B) to give the tryptamine as a colourless glass (0.1 g) which was dissolved in a hot mixture of ethanol (9 ml) and water (1 ml) and treated with a solution of creatinine and sulphuric acid (2M, 1:1, 0.15 ml). On cooling and scratching the title compound was deposited as a pale cream-coloured crystalline solid (0.1 g), m.p. 218°-221° (dec) after drying in vacuo over P2 O5 for 10 h at 60°. Analysis Found: C, 44.7; H, 6.1; N, 14.7. C17 H25 N3 O2 S.C4 H7 N3 O.H2 SO4.H2 O requires C, 44.7; H, 6.4; N, 14.9percent. Patent; Glaxo Group Limited; US4816470; (1989); (A1) English View in Reaxys

OH O

HN OH

NH 2

Rx-ID: 25161586 View in Reaxys 65/87 Yield 60%

Conditions & References 6 : N-[3-(2-Dimethylaminoethyl)-1H-indol-5-yl]urea (E)-2-Butenedioate (2:3) Hydrate (10:1) A suspension of 7.95 g (0.03 mole) of the oxalylamide, above, in 275 ml of dry THF was treated with 61 ml (0.06 mole) of 1M B2 H6 in THF. After 3 hours, the excess diborane was quenched with 1N HCl and solvents removed in vacuo. The resultant orange solid was dissolved in 250 ml of hot 20percent HCl, filtered and cooled. The precipitated product was filtered and dried to give 4.9 g (60percent yield) of the tryptamine: nmr (d6 -DMSO) δ(TMS) 8.72 (1, d, J4-6 =2 Hz, H-4), 8.10 (1, d of d, J6-7 =8 Hz, J4-6 =2 Hz, H-6), 7.60 (1, d, J6-7 =8 Hz, H-7), 7.55 (1, S, H-2), 3.32 (4, S, --CH2 CH2 --), 2.97 (3, S, N--CH3) and 2.86 (3, S, NCH3); mass spectrum (70 e/v) m/e 233. Patent; McNeilab, Inc.; US4803218; (1989); (A1) English View in Reaxys

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H 2N

Z O

OHHO

NH 2

Rx-ID: 25163336 View in Reaxys 66/87 Yield

Conditions & References 18.b : (b) The residue was purified by chromatography (F) to give the tryptamine as an oil (0.057 g) which was treated with maleic acid (0.026 g) in ethanol (5 ml) and methanol (1 ml). Solvent was evaporated and the residual oil crystallized from absolute ethanol (2 ml) to give the title compound as a light brown solid (0.03 g) m.p. 174°-175°. Analysis Found: C, 48.6; H, 5.2; N, 10.7. C11 H15 N3 O2 S.C4 H4 O4 requires C, 48.8; H, 5.2; N, 11.4percent. Patent; Glaxo Group Limited; US4816470; (1989); (A1) English View in Reaxys

Z O

O OHHO HN

HN S O O

NH 2

Rx-ID: 25163339 View in Reaxys 67/87 Yield

Conditions & References 25.b : (b) (b) 3-[2-(Methylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide, maleate, quarter hydrate To a stirred suspension of lithium aluminium hydride (0.77 g) in dry tetrahydrofuran (5 ml) in a stream of nitrogen was added a solution of the product of stage (a) (0.3 g) in dry tetrahydrofuran (10 ml). The suspension was heated under reflux for 5 h. Water (1 ml) in tetrahydrofuran (9 ml) was added to the ice cold mixture and the suspension was filtered through a pad of "hyflo". Evaporation of the filtrate gave a pale yellow gum which was chromatographed (J) to give the tryptamine as a colourless gum (0.15 g). Patent; Glaxo Group Limited; US4816470; (1989); (A1) English View in Reaxys

NH 2

Rx-ID: 25355113 View in Reaxys 68/87 Yield 69 mg (70%)

Conditions & References Reductive Amination Of An Aldehyde And A Primary Amine: 1-naphthaldehyde (51 mg, 0.33 mmol) and tryptamine (122 mg, 0.5 mmol) yielded 69 mg (70percent) MS (m/e): 301 (M+1) Patent; ELI LILLY AND COMPANY; EP818431; (1998); (A1) English View in Reaxys

O NH 2

Rx-ID: 25355170 View in Reaxys 69/87

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Yield

Conditions & References

55 mg (62%)

Reductive Amination Of An Aldehyde And A Primary Amine: salicylaldehyde (40 mg, 0.33 mmol) and tryptamine (122 mg, 0.5 mmol) yielded 55 mg (62percent) MS (m/e): 267 (M+1) Patent; ELI LILLY AND COMPANY; EP818431; (1998); (A1) English View in Reaxys

NH 2

Rx-ID: 25360487 View in Reaxys 70/87 Yield

Conditions & References

74 mg (90%)

Reductive Amination Of An Aldehyde And A Primary Amine: 2-pyridine carboxaldehyde (35 mg, 0.33 mmol) and tryptamine (122 mg, 0.5 mmol) yielded 74 mg (90percent) MS (m/e): 252 (M+1) Patent; ELI LILLY AND COMPANY; EP818431; (1998); (A1) English View in Reaxys

NH 2

Rx-ID: 26010155 View in Reaxys 71/87 Yield

Conditions & References With hydrogen, palladium on activated charcoal in 2,2,2-trifluoroethanol, Time= 3h Bailey, Patrick D.; Beard, Mark A.; Dang, Hoa P.T.; Phillips, Theresa R.; Price, Richard A.; Whittaker, James H.; Tetrahedron Letters; vol. 49; nb. 13; (2008); p. 2150 - 2153 View in Reaxys

NH O HN

NH 2

Rx-ID: 28481056 View in Reaxys 72/87 Yield 94 %

Conditions & References With pyrrolidine, samarium diiodide, water in tetrahydrofuran, T= 20 °C , Inert atmosphere Ankner, Tobias; Hilmersson, Goeran; Organic Letters; vol. 11; nb. 3; (2009); p. 503 - 506 View in Reaxys

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NH O NH

NH 2

Rx-ID: 29155829 View in Reaxys 73/87 Yield

Conditions & References With hydrazine in ethanol, T= 20 °C , Combinatorial reaction / High throughput screening (HTS) Barsanti, Paul A.; Wang, Weibo; Ni, Zhi-Jie; Duhl, David; Brammeier, Nathan; Martin, Eric; Bussiere, Dirksen; Walter, Annette O.; Bioorganic and Medicinal Chemistry Letters; vol. 20; nb. 1; (2010); p. 157 - 160 View in Reaxys

O H 2N

NH 2 O

NH 2

HO O

NH 2

N H

NH 2

H 2N

OH H

HN N H

NH 2

O HN

O OH

Rx-ID: 29255151 View in Reaxys 74/87 Yield

Conditions & References With dihydrogen peroxide, Time= 6h, T= 37 °C , pH= 4.6, Darkness, aq. borate buffer Salminen, Hanna; Heinonen, Marina; Journal of Agricultural and Food Chemistry; vol. 56; nb. 16; (2008); p. 7472 7481 View in Reaxys

NH O

HN O

NH 2

Rx-ID: 30279693 View in Reaxys 75/87 Yield ~ 94 %

Conditions & References 2 :To debenzylate a given model compound (cBz-tryptamine) in accordance with the above reaction scheme (to 3ethyl-aminoindol), the reservoir 104 of the hydrogenation apparatus 100 was filled with, as a sample solution, a stock solution of a 1:1 mixture of EtOAc:EtOH containing cBz-tryptamine in a concentration of 0.05 mol/dm3. At the same time, a catalyst of 10percent by weight bone black palladium was arranged within the reactor 110 as the catalyst packing. After this, a flow rate of 0.1 ml/s was set within the apparatus by means of the feed pump 102, while a pressure of 30 bar was generated in the flow path by means of the pressure-adjusting unit 112. During the operation of the apparatus these values were continuously maintained. The produced hydrogenate, i.e. the 3-ethyl-aminoindol was collected in the product receptacle 114, and then was subjected to an analytical assay (HPLC UV, λ=254 nm; mass spectroscopy). As a result of the analysis, we concluded that the collected hydrogenate was of the purity of 97percent, and the yield of the reaction was about 94percent. With hydrogen, palladium in ethanol, ethyl acetate, p= 22502.3Torr Patent; THALESNANO ZRT.; US2011/34704; (2011); (A1) English

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View in Reaxys

NH 2

Rx-ID: 32455913 View in Reaxys 76/87 Yield

Conditions & References

72 %

Stage 1: With formic acid, [Ru(II)(2,2’-bipyridine)3]Cl2, diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate, Nethyl-N,N-diisopropylamine in methanol, N,N-dimethyl-formamide, Time= 24h, T= 25 °C , Irradiation Stage 2: With di-tert-butyl dicarbonate, triethylamine in methanol, N,N-dimethyl-formamide, Time= 12h, T= 25 °C Chen, Yiyun; Kamlet, Adam S.; Steinman, Jonathan B.; Liu, David R.; Nature Chemistry; vol. 3; nb. 2; (2011); p. 146 - 153 View in Reaxys

NH Br NH 2

Rx-ID: 33638128 View in Reaxys 77/87 Yield

Conditions & References Reaction Steps: 3 1.1: trichlorophosphate / 0.5 h / 0 °C 1.2: 0.5 h / 20 °C 1.3: 2 h / 20 °C / Cooling with ice 2.1: ammonium acetate / 1.5 h / Reflux 3.1: lithium aluminium tetrahydride With lithium aluminium tetrahydride, ammonium acetate, trichlorophosphate Ishiyama, Haruaki; Yoshizawa, Kazuaki; Kobayashi, Jun'ichi; Tetrahedron; vol. 68; nb. 31; (2012); p. 6186 6192 View in Reaxys

N O

NH 2

Rx-ID: 33638149 View in Reaxys 78/87 Yield

Conditions & References With lithium aluminium tetrahydride Ishiyama, Haruaki; Yoshizawa, Kazuaki; Kobayashi, Jun'ichi; Tetrahedron; vol. 68; nb. 31; (2012); p. 6186 6192 View in Reaxys

NH Br O

NH 2

Rx-ID: 33638156 View in Reaxys 79/87 Yield

Conditions & References Reaction Steps: 2 1: ammonium acetate / 1.5 h / Reflux

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2: lithium aluminium tetrahydride With lithium aluminium tetrahydride, ammonium acetate Ishiyama, Haruaki; Yoshizawa, Kazuaki; Kobayashi, Jun'ichi; Tetrahedron; vol. 68; nb. 31; (2012); p. 6186 6192 View in Reaxys

NH NH

NH 2

Rx-ID: 33803014 View in Reaxys 80/87 Yield

Conditions & References

81 %

With NH4Br, ethylenediamine, Time= 5h, T= 80 °C , Microwave irradiation, Inert atmosphere, neat (no solvent) Shimizu, Yuhei; Morimoto, Hiroyuki; Zhang, Ming; Ohshima, Takashi; Angewandte Chemie - International Edition; vol. 51; nb. 34; (2012); p. 8564 - 8567 View in Reaxys

NH N S+

Cl –

NH 2

HO O O

NH 2

Rx-ID: 36203975 View in Reaxys 81/87 Yield

Conditions & References With Saccharomyces cerevisiae wild type strain V328, Time= 0.333333h, UV-irradiation Bracchitta, Giuseppina; Catalfo, Alfio; De Guidi, Guido; Photochemical and Photobiological Sciences; vol. 12; nb. 6; (2013); p. 967 - 973 View in Reaxys

NH O

NH 2

Rx-ID: 36203976 View in Reaxys 82/87 Yield

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N N O HO

NH 2

HO HO

O O

N N

O NH 2

Rx-ID: 38578681 View in Reaxys 83/87 Yield

Conditions & References in aq. phosphate buffer, T= 59 - 121 °C , pH= 6.8, Kinetics Zhou, Xin; Chou, Tsui-Fen; Aubol, Brandon E.; Park, Chin Ju; Wolfenden, Richard; Adams, Joseph; Wagner, Carston R.; Biochemistry; vol. 52; nb. 20; (2013); p. 3588 - 3600 View in Reaxys

O H 2N

NH 2

N H

Rx-ID: 38715371 View in Reaxys 84/87 Yield

Conditions & References

72 %

General “One-Pot” Procedure for the Decarboxylation of Amino Acids General procedure: General “One-Pot” Procedure for the Decarboxylation of Amino Acids [0045] A magnetic stir bar, 3 mL of n-PrOH, 10 mmol of R-Carvone, and 5 mmol of amino acid were charged to a pressure vessel. The vessel was heated from room temperature to 190° C. over 5 min with stirring. If necessary the reaction vessel was maintained at 190° C. for additional time until the slurry became clear. The vessel was allowed to cool to below the solvent boiling point, carefully vented to release evolved CO2, and 10 mL of 2M HCl was added. The vessel was heated to 190° C. over 5 min with stirring and allowed to cool. The aqueous reaction mixture was washed three times with 25 mL of ether and water solvent distilled off from the hydrochloride salt. The hydrochloride salt was transferred to a vacuum oven and dried overnight at 150° C. and 10 Torr. The hydrochloride salt was then weighed and analyzed via IR and NMR.; tryptamine hydrochloride, δH 2.97 2H t J=9, 3.13 2H t J=8, 7.01 1H t J=4, 7.07-7.12 2H m, 7.34 1H d J=4, 7.49 1H d J=4; δC 22.88, 40.03, 109.36, 112.30, 118.54, 119.68, 122.44, 124.53, 126.70, 136.69 Stage 1: With (-)-Carvone in propan-1-ol, Time= 0.15h, T= 190 °C , p= 11251.1Torr , Sealed tube Stage 2: With hydrogenchloride in propan-1-ol, water, Time= 0.0833333h, T= 190 °C Patent; Morrison, Richard W.; Jackson, Douglas Michael; US2014/275569; (2014); (A1) English View in Reaxys

N H

NH Cl

NH 2

Rx-ID: 41474893 View in Reaxys 85/87 Yield 74 %

Conditions & References General Decarboxylation Procedure General procedure: A magnetic stir bar, 3 mL of n-PrOH, 10 mmol of R-carvone, and 5 mmol of amino acid were charged to a pressure vessel. The vessel was heated from room temperature to 190°C over 5 min with stirring. If necessary the reaction vessel was maintained at 190°C for an additional time until the slurry became clear. The vessel was allowed to cool to below the solvent boiling point, carefully vented to release evolved CO2, and analyzed via GC-MS to verify the presence of decarboxylated imine. Ten mL of 2M HCl was then added in a one-pot fashion, and, in all cases but threonine, the reaction vessel was heated to 190°Cover 5 min with stirring and then allowed to cool. In the case of the temperature-sensitive threonine, soxhlet extraction with toluene was performed at 80°C to remove

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R-carvone from the reaction mixture. The aqueous reaction mixture was washed three times with 25 mL of ether, and then water solvent was distilled off from the hydrochloride salt. The hydrochloride salt was transferred to a vacuum oven and dried overnight at 150 °C and 10 Torr. Stage 1: With (R)-Carvone in propan-1-ol, T= 0 - 190 °C , Green chemistry Stage 2: With hydrochlorid acid in propan-1-ol, water, Time= 0.0833333h, T= 190 °C , Microwave irradiation, Green chemistry Jackson, Douglas M.; Ashley, Robert L.; Brownfield, Callan B.; Morrison, Daniel R.; Morrison, Richard W.; Synthetic Communications; vol. 45; nb. 23; (2015); p. 2691 - 2700 View in Reaxys

NH 2

Rx-ID: 41474900 View in Reaxys 86/87 Yield

Conditions & References

72 %

General Decarboxylation Procedure General procedure: Ten mL of 2M HCl was then added in a one-pot fashion, and, in all cases but threonine, the reaction vessel was heated to 190°Cover 5 min with stirring and then allowed to cool. In the case of the temperaturesensitive threonine, soxhlet extraction with toluene was performed at 80°C to remove R-carvone from the reaction mixture. The aqueous reaction mixture was washed three times with 25 mL of ether, and then water solvent was distilled off from the hydrochloride salt. The hydrochloride salt was transferred to a vacuum oven and dried overnight at 150 °C and 10 Torr. With hydrochlorid acid in propan-1-ol, Time= 0.15h, T= 190 °C , Green chemistry, Temperature Jackson, Douglas M.; Ashley, Robert L.; Brownfield, Callan B.; Morrison, Daniel R.; Morrison, Richard W.; Synthetic Communications; vol. 45; nb. 23; (2015); p. 2691 - 2700 View in Reaxys

O OH

NH 2

Rx-ID: 42202953 View in Reaxys 87/87 Yield

Conditions & References Reaction Steps: 2 1: benzotriazol-1-ol; dicyclohexyl-carbodiimide; 4-methyl-morpholine; ammonium chloride / N,N-dimethyl-formamide / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 3 h / 20 °C / |Inert atmosphere With 4-methyl-morpholine, lithium aluminium tetrahydride, ammonium chloride, benzotriazol-1-ol, dicyclohexyl-carbodiimide in tetrahydrofuran, N,N-dimethyl-formamide Fantacuzzi, Marialuigia; Maccallini, Cristina; Di Matteo, Mauro; Ammazzalorso, Alessandra; Bruno, Isabella; De Filippis, Barbara; Giampietro, Letizia; Mollica, Adriano; Amoroso, Rosa; Journal of Pharmaceutical and Biomedical Analysis; vol. 120; (2016); p. 419 - 424 View in Reaxys

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