反应详情

To a crude solution of (S)-4-nitrophenyl 1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethylcarbamate in DCM (1 mL) (29 mg, 0.053 mmol) was added 3,3-difluorocyclopentanamine hydrochloride (17 mg, 0.106 mmol). The reaction mixture was stirred at room temperature for 2 h and the solution turned yellow. The solution was diluted with CH2Cl2 (1 mL) and washed with 1N NaOH (3×1 mL), dried over Na2SO4, and concentrated. The yellow residue was purified by flash chromatography (4 g SiO2, 0-40% EtOAc/hexane) to furnish 1-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-(3,3-difluorocyclopentyl)urea as a white solid (13 mg, 45%). LCMS: 4.06 min [M+1] 542.2 (4 min gradient, MeOH/H2O 0.1% NH4OAc) LC/MS: [M+H]=542.2 1H NMR (CDCl3, 400 MHz): 8.26 (m, 1H), 7.67 (dd, J=2 Hz, J=4 Hz, 1H), 7.52 (br, 1H), 7.38 (m, 1H), 7.22 (m, 1H), 7.18-7.08 (m, 5H), 6.57 (m, 2H), 4.50 (d, J=8 Hz, 1H), 4.46 (dd, J=4 Hz, J=8 Hz, 1H), 4.25 (m, 1H), 3.55 (d, J=12 Hz, 1H), 2.65-1.54 (m, 6H).

1. washwashed with 1N NaOH (3×1 mL)
2. dry with materialdried over Na2SO4
3. concentrationconcentrated
4. customThe yellow residue was purified by flash chromatography (4 g SiO2, 0-40% EtOAc/hexane)