反应详情

A sample of {1-(S)-[1-(R)-Benzyloxymethyl-2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-2-cyclohexyl-ethyl}-carbamic acid tert-butyl ester (210 mg, 0.34 mmol) was treated with a mixture of trifluoroacetic acid, dichloromethane and water (45:45:10) and allowed to age for 2 hours. The solvent was then removed by rotary evaporation. The resulting oil was treated with m-anisic acid (75 mg, 0.49 mmol), HATU (187 mg, 0.49 mmol) and dichloromethane (2 mL). The reaction was then treated with diisopropylethylamine (245 mg, 1.9 mmol) and stirred for 2 hours. The reaction was diluted with ethyl acetate, extracted with saturated aqueous NaHCO3 twice, dried over MgSO4 and the solvent was removed. The resulting oil was purified over silica gel using a gradient of 0 to 100% ethyl acetate in hexane to afford 195 mg (87%) of the title material; 1H NMR (CDCl3, 400 MHz) δ 0.84-1.03 (m, 2H), 1.06-1.22 (m, 3H), 1.32-1.45 (m, 1H), 1.58-1.87 (m, 7H), 2.92 (dd, 1H, J1=J2=8.2), 3.13-3.25 (m, 2H), 3.31-3.46 (m, 2H), 3.54 (dd, 1H, J1=54.2, J2=9.4), 3.68 (dd, 1H, J1=2.4, J2=9.3), 3.84 (s, 3H), 4.26-4.36 (m, 1H), 4.53 (dd, 2H, J1=11.8, J2=26.0), 4.65-4.74 (m, 1H), 6.46 (dd, 1H, J1=4.1, J2=8.4), 6.46 (d, 1H, J=8.3), 6.69-6.83 (m, 2H), 7.02-7.09 (m, 1H), 7.27-7.39 (m, 7H); HPLC-MS calcd. for C35H42FN3O4 (M+H+) 587.3, found 587.5.

1. customThe solvent was then removed by rotary evaporation
2. extractionextracted with saturated aqueous NaHCO3 twice
3. dry with materialdried over MgSO4
4. customthe solvent was removed
5. customThe resulting oil was purified over silica gel using a gradient of 0 to 100% ethyl acetate in hexane