反应详情

A solution of diethyl (3-methoxy-4-{[4-{[2-(methylcarbamoyl)phenyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (Example 53, 44.3 mg, 0.0781 mmol) in 37% HCl (1 mL) was heated at 80° C. for a total of 3.5 h. The reaction was concentrated in vacuo. The residue was dissolved in DMSO and submitted for mass-directed purification (under basic conditions; ammonium bicarbonate buffer, pH 9). The fractions containing product were combined and concentrated in vacuo, giving the title material as a white solid, 11.6 mg (27%). 1H NMR (400 MHz, MeOD) δ ppm: 8.33 (d, J=8.3 Hz, 1H), 8.29 (s, 1H), 7.85 (d, J=8.1 Hz, 1H), 7.62 (dd, J=7.8, 1.3 Hz, 1H), 7.49 (ddd, J=8.5, 7.4, 1.5 Hz, 1H), 7.18 (td, J=7.6, 1.0 Hz, 1H), 7.05 (t, J=1.8 Hz, 1H), 6.79 (ddd, J=8.1, 2.0, 1.8 Hz, 1H), 3.89 (s, 3H), 3.79-3.88 (m, 2H), 2.96 (d, J=20.2 Hz, 2H), 2.89 (s, 3H), 1.19 (t, J=6.9 Hz, 3H). MS (ES+): m/z 540.14 (100) [MH+]. HPLC: tR=2.63 min (ZQ3, polar—5 min).

1. concentrationThe reaction was concentrated in vacuo
2. dissolutionThe residue was dissolved in DMSO
3. customsubmitted for mass-directed purification (under basic conditions; ammonium bicarbonate buffer, pH 9)
4. additionThe fractions containing product
5. concentrationconcentrated in vacuo