pent-4-yn-1-amine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of pent-4-ynylamine (480 mg; Li, Y. et al. J. Am. Chem. Soc. 1996, 118, 9295) in DCM (5 mL) was treated with (BOC)2O at rt for 15 min. Evaporation gave the title compound as a colorless oil. 1H NMR (CDCl3) δ 4.68 (s, 1H), 3.24 (q, 2H), 2.25 (td, 2H), 1.97 (t, 1H), 1.70 (quint., 2H), 1.45 (s, 9H). Evaporation

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of N-cyano-N'-{2-[(4-methyl-5-imidazolyl)methylthio]ethyl}-S-methylisothiourea (3.00 g., 0.0111 mole) and 4-pentyn-1-amine (3.69 g., 0.0445 mole) in 60 ml. of acetonitrile was stirred at reflux for 24 hours, and then allowed to stand at room temperature for 96 hours. The solvent and excess amine were removed under reduced pressure and the residual yellow gum was purified by chromatography on 50 g. of 100-200 mesh silica gel, using gradient elution with methylene chloride/methanol (99:1-96:4). The middle fractions indicated by TLC to be pure were combined and evaporated to give 1.91 g. of yellow gum which was crystallized at -15° C. from 18 ml. of ethyl acetate. The resulting white solid (1.25 g.) was recrystallized at -15° C. from 10 ml. of acetonitrile to give 1.063 g. of product; m.p. 99°-103° C. at reflux for 24 hours The solvent and excess amine were removed under reduced pressure the residual yellow gum was purified by chromatography on 50 g elution with methylene chloride/methanol (99:1-96:4) evaporated to give 1.91 g of yellow gum which was crystallized at -15° C. from 18 ml The resulting white solid (1.25 g.) was recrystallized at -15° C. from 10 ml of acetonitrile to give 1.063 g

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 500 mL round bottom flask was charged with 2-(S)-(2,2,2-trifluoroacetylamino)-butyric acid (5.0 g, 0.025 mol), 1-hydroxybenzotriazole hydrate (4.5 g, 0.033 mol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (6.4 g, 0.033 mol), 4-(dimethylamino)pyridine (0.02 g, 0.163 mmol), and dimethylformamide (95 mL). To the resulting mixture was then added triethylamine (10.6 mL, 0.076 mol) and pent-4-yn-1-amine (2.7 g, 0.033 mol). The resulting mixture was stirred at room temperature for 22 h, then concentrated in vacuo to yield a residue which was purified via flash silica gel chromatography (Analogix IF-280, SF65-400 g column, gradient 90:10-40:60 Heptane:EtOAc) to yield (S)—N-(pent-4-ynyl)-2-(2,2,2-trifluoroacetamido)butanamide. 1H NMR (300 MHz, CDCl3) δ4.46-4.53 (m, 1H), 3.32-3.48 (m, 2H), 2.23-2.29 (m, 2H), 2.00 (s, 1H), 1.86-1.98 (m, 2H), 1.71-1.83 (m, 2H), and 0.91-0.98 (m, 3H). concentrated in vacuo to yield a residue which was purified via flash silica gel chromatography (Analogix IF-280

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add triethylamine (0.434 mL; 2.0 equiv; 3.12 mmoles) followed by 4-pentyn-1-amine (0.194 mL; 1.50 equiv; 2.34 mmoles) to a solution of 2-chloro-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]ethanone (0.534 g; 1.0 equiv; 1.56 mmoles) in tetrahydrofuran (5.19 mL). Stir for 48 hours at 55° C. The solution was directly concentrated to afford 1-[2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-2-(pent-4-ynylamino)ethanone (0.606 g; 100%): MS (m/z): 390(M+1). The solution was directly concentrated

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add triethylamine (0.434 mL; 2.0 equiv; 3.12 mmoles) followed by 4-pentyn-1-amine (0.194 mL; 1.50 equiv; 2.34 mmoles) to a solution of 2-chloro-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]ethanone (0.534 g; 1.0 equiv; 1.56 mmoles) in tetrahydrofuran (5.19 mL). Stir for 48 hours at 55° C. The solution was directly concentrated to afford 1-[2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-2-(pent-4-ynylamino)ethanone (0.606 g; 100%): MS (m/z): 390(M+1). The solution was directly concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 1,1′-carbonyldiimidazole (0.539 mg 1.05 equiv; 3.26 mmoles) slowly portion wise to a −78° C. solution of 4-pentyn-1-amine (0.258 mL; 1.0 equiv; 3.10 mmoles) in dichloromethane (10 mL). Allow the reaction to warm to ambient temperature and stir for 72 hours. Use the solution directly for subsequent chemistry: MS (m/z): 178(M+1). the reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 1,1′-carbonyldiimidazole (0.539 mg 1.05 equiv; 3.26 mmoles) slowly portion wise to a −78° C. solution of 4-pentyn-1-amine (0.258 mL; 1.0 equiv; 3.10 mmoles) in dichloromethane (10 mL). Allow the reaction to warm to ambient temperature and stir for 72 hours. Use the solution directly for subsequent chemistry: MS (m/z): 178(M+1). the reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of N-cyano-N'-{2-[(4-methyl-5-imidazolyl)methylthio]ethyl}-S-methylisothiourea (3.00 g., 0.0111 mole) and 4-pentyn-1-amine (3.69 g., 0.0445 mole) in 60 ml. of acetonitrile was stirred at reflux for 24 hours, and then allowed to stand at room temperature for 96 hours. The solvent and excess amine were removed under reduced pressure and the residual yellow gum was purified by chromatography on 50 g. of 100-200 mesh silica gel, using gradient elution with methylene chloride/methanol (99:1-96:4). The middle fractions indicated by TLC to be pure were combined and evaporated to give 1.91 g. of yellow gum which was crystallized at -15° C. from 18 ml. of ethyl acetate. The resulting white solid (1.25 g.) was recrystallized at -15° C. from 10 ml. of acetonitrile to give 1.063 g. of product; m.p. 99°-103° C. at reflux for 24 hours The solvent and excess amine were removed under reduced pressure the residual yellow gum was purified by chromatography on 50 g elution with methylene chloride/methanol (99:1-96:4) evaporated to give 1.91 g of yellow gum which was crystallized at -15° C. from 18 ml The resulting white solid (1.25 g.) was recrystallized at -15° C. from 10 ml of acetonitrile to give 1.063 g

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of N-cyano-N'-{2-[(4-methyl-5-imidazolyl)methylthio]ethyl}-S-methylisothiourea (3.00 g., 0.0111 mole) and 4-pentyn-1-amine (3.69 g., 0.0445 mole) in 60 ml. of acetonitrile was stirred at reflux for 24 hours, and then allowed to stand at room temperature for 96 hours. The solvent and excess amine were removed under reduced pressure and the residual yellow gum was purified by chromatography on 50 g. of 100-200 mesh silica gel, using gradient elution with methylene chloride/methanol (99:1-96:4). The middle fractions indicated by TLC to be pure were combined and evaporated to give 1.91 g. of yellow gum which was crystallized at -15° C. from 18 ml. of ethyl acetate. The resulting white solid (1.25 g.) was recrystallized at -15° C. from 10 ml. of acetonitrile to give 1.063 g. of product; m.p. 99°-103° C. at reflux for 24 hours The solvent and excess amine were removed under reduced pressure the residual yellow gum was purified by chromatography on 50 g elution with methylene chloride/methanol (99:1-96:4) evaporated to give 1.91 g of yellow gum which was crystallized at -15° C. from 18 ml The resulting white solid (1.25 g.) was recrystallized at -15° C. from 10 ml of acetonitrile to give 1.063 g

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 500 mL round bottom flask was charged with 2-(S)-(2,2,2-trifluoroacetylamino)-butyric acid (5.0 g, 0.025 mol), 1-hydroxybenzotriazole hydrate (4.5 g, 0.033 mol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (6.4 g, 0.033 mol), 4-(dimethylamino)pyridine (0.02 g, 0.163 mmol), and dimethylformamide (95 mL). To the resulting mixture was then added triethylamine (10.6 mL, 0.076 mol) and pent-4-yn-1-amine (2.7 g, 0.033 mol). The resulting mixture was stirred at room temperature for 22 h, then concentrated in vacuo and the resulting residue purified via flash silica gel chromatography (Analogix IF-280, SF65-400 g column, gradient 90:10-40:60 Heptane:EtOAc) to yield (S)—N-(pent-4-ynyl)-2-(2,2,2-trifluoroacetamido)butanamide. 1H NMR (300 MHz, CDCl3) δ 4.46-4.53 (m, 1H), 3.32-3.48 (m, 2H), 2.23-2.29 (m, 2H), 2.00 (s, 1H), 1.86-1.98 (m, 2H), 1.71-1.83 (m, 2H), and 0.91-0.98 (m, 3H). concentrated in vacuo the resulting residue purified via flash silica gel chromatography (Analogix IF-280