反应详情

温度

80 °C

A solution of ethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)propan-2-ylphosphinate (Compound 68D, 1.00 g, 2.21 mmol) and 3-amino-6-bromo-N-methylpyridine-2-carboxamide (Compound 6D, 0.516 g, 2.24 mmol) in TFE (11.71 mL) was charged with TFA (0.341 mL, 4.43 mmol). The reaction mixture was heated at 80° C. for 16 hours. The reaction mixture was concentrated under reduced pressure to a light yellow oil. The crude material was purified using a Teledyne ISCO Combiflash® Rf system using DCM/MeOH (100:0→95:5) as eluent to afford the desired product as a white solid (865 mg, 61%). 1H NMR (CDCl3, 400 MHz): δ 12.97 (br. s., 1H), 8.85 (d, J=9.3 Hz, 1H), 8.29 (s, 1H), 8.13 (q, J=4.4 Hz, 1H), 7.66 (br. s., 1H), 7.59 (d, J=9.1 Hz, 1H), 7.02 (t, J=1.6 Hz, 1H), 6.88 (td, J=1.8, 8.2 Hz, 1H), 3.92-4.10 (m, 2H), 3.87 (s, 3H), 3.19 (dd, J=2.8, 14.9 Hz, 2H), 3.04 (d, J=5.3 Hz, 3H), 1.87-2.00 (m, 1H), 1.18-1.27 (m, 9H). MS (ESI): m/z 645.55/647.54 [M+H]+. UPLC: tR=1.47 min (UPLC-SQD: analytical—2 min).

1. concentrationThe reaction mixture was concentrated under reduced pressure to a light yellow oil
2. customThe crude material was purified