4,4-difluoroazepane;hydrochloride

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

実験手順: 5-Phenyl-thiophene-3-carboxylic acid (0.20 g, 1.11 mmol) and 4,4-difluoro-azepane hydrochloride (0.19 g, 1.11 mmol) were stirred in acetonitrile (10 mL) with silica-supported diethylamine (1.32 mmol/g, 2.5 g) and HATU (0.40 g, 1.11 mmol) for 18 hours. The reaction mixture was filtered and the solvent was removed by evaporation then the crude material was purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid) over 20 minutes. The fractions containing the desired product were evaporated to give the title compound as a gum (0.15 g). LCMS m/z 322.19 [M+H]+ R.T.=11.14 min (Analytical Method 2). The reaction mixture was filtered the solvent was removed by evaporation the crude material was purified by HPLC eluting with 10%-98% acetonitrile in water (0.1% formic acid) over 20 minutes The fractions containing the desired product were evaporated

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

実験手順: Acetyl chloride (3.9 mL) was added to methanol (90 mL) at 0° C. and stirred for 20 minutes before addition of 4,4-difluoro-azepane-1-carboxylic acid tert-butyl ester as a solution in methanol (10 mL). After 30 minutes, HCl in dioxane (4 N, 40 mL) was added cautiously and the mixture was stirred at room temperature for 3 hours. The solution was concentrated, triturated with ether, filtered and dried under vacuum overnight to afford the title compound as an off-white solid (2.1 g). 1H NMR (400 MHz, DMSO): δ 9.5 (s, 2H), 3.2-3.1 (m, 4H), 2.5-2.4 (m, 2H), 2.3-2.2 (m, 2H), 1.9-1.8 (m, 2H). The solution was concentrated triturated with ether filtered dried under vacuum overnight

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

実験手順: 5-Phenyl-thiophene-3-carboxylic acid (0.20 g, 1.11 mmol) and 4,4-difluoro-azepane hydrochloride (0.19 g, 1.11 mmol) were stirred in acetonitrile (10 mL) with silica-supported diethylamine (1.32 mmol/g, 2.5 g) and HATU (0.40 g, 1.11 mmol) for 18 hours. The reaction mixture was filtered and the solvent was removed by evaporation then the crude material was purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid) over 20 minutes. The fractions containing the desired product were evaporated to give the title compound as a gum (0.15 g). LCMS m/z 322.19 [M+H]+ R.T.=11.14 min (Analytical Method 2). The reaction mixture was filtered the solvent was removed by evaporation the crude material was purified by HPLC eluting with 10%-98% acetonitrile in water (0.1% formic acid) over 20 minutes The fractions containing the desired product were evaporated

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

実験手順: Acetyl chloride (3.9 mL) was added to methanol (90 mL) at 0° C. and stirred for 20 minutes before addition of 4,4-difluoro-azepane-1-carboxylic acid tert-butyl ester as a solution in methanol (10 mL). After 30 minutes, HCl in dioxane (4 N, 40 mL) was added cautiously and the mixture was stirred at room temperature for 3 hours. The solution was concentrated, triturated with ether, filtered and dried under vacuum overnight to afford the title compound as an off-white solid (2.1 g). 1H NMR (400 MHz, DMSO): δ 9.5 (s, 2H), 3.2-3.1 (m, 4H), 2.5-2.4 (m, 2H), 2.3-2.2 (m, 2H), 1.9-1.8 (m, 2H). The solution was concentrated triturated with ether filtered dried under vacuum overnight