Methanol → HCID 178466845, compound

Participants

Reaction Steps

Ethyl trans-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 245, 23.4 mg, 0.031 mmol) was taken up in THF (0.042 mL, 0.52 mmol) and MeOH (0.042 mL, 1.0 mmol). This was treated with a solution of lithium hydroxide, monohydrate (6.57 mg, 0.16 mmol) in H2O (0.042 mL, 2.30 mmol) and 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 22.3 mg (99%) of the desired product. 1H NMR (400 MHz, MeOD) δ ppm 4.54 (s, 1 H), 4.05-4.21 (m, 6 H), 3.29 (s, 2 H), 3.20 (s, 3 H), 2.60-2.69 (m, 1 H), 2.38-2.48 (m, 1 H), 2.15 (d, J=11.87 Hz, 2H), 1.91-1.98 (m, 2 H), 1.56-1.77 (m, 4 H), 1.43 (t, J=6.95 Hz, 3 H), 1.30 (t, 6 H). MS (ES+): m/z 720.22/721.25 (100/98) [MH+]. HPLC: tR=1.54 min (Micromass TOF: polar—3 min).

Provenance & Evidence