反应详情

To a solution of 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluoroaniline (50 mg, 93.6 μmol) and (S)-4-t-butoxy-2-(t-butoxycarbonylamino)-4-oxobutanoic acid (2.4 equiv, 66 mg, 0.244 mmol) in DCM (3 mL) was added HATU (2.2 equiv, 80 mg, 0.204 mmol) followed by DIPEA (3.0 equiv, 49 mL, 0.281 mmol). The mixture was stirred at room temperature overnight. Purification by column chromatography provided the protected product. Deprotection was performed by stirring with TFA (1 mL) and DCM (1 mL) for 1 h. Purification by HPLC using NH4CO3 as a modifier afforded the title compound as a white solid (11 mg, 18%). 1H NMR (400 MHz, MeOD) δ 7.43 (s, 1H), 7.37 (d, J=11.6 Hz, 1H), 7.25 (s, 1H), 7.18 (d, J=8.4 Hz, 1H), 6.80 (m, 2H), 6.56-6.49 (m, 2H), 6.38-6.30 (m, 1H), 6.22 (m, 1H), 4.19 (t, J=7.6, 1H), 4.00 (dd, J=13.5, 7.4 Hz, 2H), 3.71 (s, 3H), 2.89-2.78 (m, 1H), 2.67 (dd, J=17.0, 8.1 Hz, 1H), 1.54 (s, 3H), 1.53 (s, 3H); MS (EI) m/z 649 (MH+).

1. customPurification by column chromatography
2. customprovided the protected product
3. customPurification by HPLC