反应详情

Ethyl cis-4-(7-{[2-({4-[(diethoxyphosphoryl)methyl]-2-ethoxyphenyl}amino)-5-(trifluoromethyl)pyrimidin-4-yl]amino}-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohexanecarboxylate (Example 244, 72.0 mg, 0.096 mmol) was taken up in THF (0.13 mL, 1.60 mmol) and MeOH (0.13 mL, 3.20 mmol). This was treated with a solution of lithium hydroxide, monohydrate (20.2 mg, 0.48 mmol) in H2O (0.13 mL, 7.2 mmol) and was allowed to stir at rt for 30 hrs. The reaction was concentrated in vacuo to a solid and was purified by CombiFlash®Rf 4X Organic Purification System [24 g RediSep® Normal-phase GOLD Silica Flash Column, dried loaded, elution gradient: 0→5% MeOH in DCM] to afford 68.6 mg (99%) of the desired product. 1H NMR (400 MHz, MeOD) δ ppm 8.43 (d, J=9.09 Hz, 1H), 8.34 (s, 1H), 7.88 (d, J=8.34 Hz, 1H), 7.26 (d, J=8.84 Hz, 1H), 7.03 (t, J=2.02 Hz, 1H), 6.90 (dt, J=8.21, 2.21 Hz, 1H), 4.51 (s, 2H), 4.03-4.17 (m, 6H), 3.27 (s, 2H), 3.18 (s, 3H), 2.74 (br. s., 1H), 2.61-2.70 (m, 1H), 2.30 (d, J=12.38 Hz, 2H), 1.66-1.82 (m, 6H), 1.41 (t, J=6.95 Hz, 3H), 1.28 (t, J=7.07 Hz, 6H). MS (ES+): m/z 720.22/721.26 (100/98) [MH+]. HPLC: tR=1.62 min (Micromass TOF: polar—3 min).

1. concentrationThe reaction was concentrated in vacuo to a solid
2. customwas purified by CombiFlash®Rf 4X Organic Purification System [24 g RediSep® Normal-phase GOLD Silica Flash Column, dried loaded, elution gradient: 0→5% MeOH in DCM]