C(OC([N:8]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([NH:19][CH:20]([C:25]3[CH:30]=[CH:29][C:28]([Br:31])=[CH:27][N:26]=3)[C:21]([F:24])([F:23])[F:22])=[CH:15][CH:14]=2)[CH2:9]1)=O)(C)(C)C.Cl>C1COCC1.O1CCOCC1.C(OCC)(=O)C.C1COCC1>[Br:31][C:28]1[CH:29]=[CH:30][C:25]([CH:20]([NH:19][C:16]2[CH:17]=[CH:18][C:13]([CH:10]3[CH2:11][CH2:12][NH:8][CH2:9]3)=[CH:14][CH:15]=2)[C:21]([F:22])([F:24])[F:23])=[N:26][CH:27]=1To a stirred solution of (RS)-3-{4-[(RS)-1-(5-bromo-pyridin-2-yl)-2,2,2-trifluoro-ethylamino]-phenyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (27 mg) in THF (1 ml) was added dropwise a solution of hydrogen chloride in dioxane (0.20 ml, 4 M solution) and the mixture was heated at 60° C. for 4 hours. The mixture was then cooled to room temperature, diluted with ethyl acetate/THF (1:1), and washed sequentially with 2 N aq. sodium hydroxide solution and with saturated brine. The organic phase was separated, dried over sodium sulphate, and concentrated in vacuo. The reside was purified by flash column chromatography (silical gel; gradient: heptane/dichloromethane/methanol) to give [(RS)-1-(5-bromo-pyridin-2-yl)-2,2,2-trifluoro-ethyl]-((RS)-4-pyrrolidin-3-yl-phenyl)-amine (12 mg, 56%) as a yellow amorphous solid. MS (ISP): 402.1 ([{81Br}M+H]+), 400.1 ([{79Br}M+H]+).
読み込み中…
