反应详情

The title product was prepared according to the procedure for Example 102 using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (203.1 mg, 0.4793 mmol) and 8-amino-2-methylisoquinolin-1(2H)-one (Compound 131A, 100.0 mg, 0.5740 mmol). The crude product was purified using the Teledyne/ISCO Combiflash system, eluting with 0-5% MeOH:CH2Cl2. The desired fractions were pooled together and concentrated in vacuo, yielding the title material as a yellow solid, 225.9 mg (82%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.23 (br s, 1H), 9.88 (s, 1H), 8.87 (br s, 1H), 8.48 (s, 1H), 7.55-7.68 (m, 3H), 7.53 (d, J=7.1 Hz, 1H), 7.31 (d, J=7.1 Hz, 1H), 7.24 (dd, J=8.6, 2.3 Hz, 2H), 6.70 (d, J=7.3 Hz, 1H), 3.91-4.01 (m, 4H), 3.53 (s, 3H), 3.20 (d, J=21.2 Hz, 2H), 1.18 (t, J=6.9 Hz, 6H). MS (ES+): m/z 562.11 (100) [MH+]. HPLC: tR=3.58 min (ZQ3, polar—5 min).

1. customThe crude product was purified
2. washeluting with 0-5% MeOH
3. concentrationconcentrated in vacuo