反应详情

A solution of N-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-methylphenyl)-3-(trifluoromethyl)piperazine-1-carboxamide D11 (0.05 mmol), HCHO (0.15 mmol, 30% aqueous) and anhydrous Na2SO4 (1.5 mmol) in DCM (2 mL) is stirred at rt for 30 min. Then NaHB(OAc)3 (0.3 mmol) is added and the resulting mixture is stirred for 12 h. Purification by prep-HPLC (ACN gradient 10-70%) affords N-(5-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-methylphenyl)-3-(trifluoromethyl)-4-methylpiperazine-1-carboxamide D12 as a TFA salt. 1H NMR (400 MHz, d6-DMSO) δ 9.69 (s, 1H), 8.80 (s, 2H), 8.15 (s, 1H), 7.76 (d, J=8.8 Hz, 2H), 7.61 (s, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.28 (t, J=74.0 Hz, 1H), 7.27 (d, J=8.8 Hz, 2H), 7.09 (d, J=8.4 Hz, 1H), 3.68 (m, 1H), 3.54 (m, 1H), 2.88 (m, 1H), 2.51 (m, 4H), 2.47 (s, 1H), 2.09 (s, 3H). MS (m/z) (M+1)+: 537.2.

1. customPurification by prep-HPLC (ACN gradient 10-70%)