反应详情

A solution of diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (119.5 mg, 0.26 mmol) and ethyl cis-4-(7-amino-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohexanecarboxylate (100 mg, 0.32 mmol) in TFE (2.39 mL, 32.8 mmol) was treated with TFA (90.1 mg, 0.790 mmol) and irradiated on the microwave at 105° C. for 30 minutes. The reaction mixture was concentrated under reduced pressure to a solid. The material was purified on a CombiFlash®Rf 4X Organic Purification System [24 g RediSep® Normal-phase GOLD Silica Flash Column, dry loaded, elution gradient: 0→5% MeOH in 1:1 DCM/EtOAc] to afford 74 mg (38%) of the desired product. 1H NMR (400 MHz, MeOD) δ ppm 8.46 (br. s., 1H), 8.35 (s, 1H), 7.89 (d, J=8.08 Hz, 1H), 7.26 (d, J=8.84 Hz, 1H), 7.08 (t, J=2.02 Hz, 1H), 6.94 (dt, 1H), 4.52 (s, 2H), 4.26 (q, J=7.07 Hz, 2H), 4.11 (quin, J=7.26 Hz, 4H), 3.92 (s, 3H), 3.36 (br. s., 1H), 3.30 (br. s., 1H), 3.20 (s, 3H), 2.79 (br. s., 1H), 2.68 (br. s., 1H), 2.28-2.33 (m, 2H), 2.30 (d, J=6.82 Hz, 2H), 1.77 (d, J=5.81 Hz, 6H), 1.27-1.37 (m, 9H). MS (ES+): m/z=734.23 [MH+]. HPLC: tR=1.77 min (UPLC TOF, polar—3 min).

1. customirradiated on the microwave at 105° C. for 30 minutes
2. concentrationThe reaction mixture was concentrated under reduced pressure to a solid
3. customThe material was purified on a CombiFlash®Rf 4X Organic Purification System [24 g RediSep® Normal-phase GOLD Silica Flash Column, dry loaded, elution gradient: 0→5% MeOH in 1:1 DCM/EtOAc]