反应详情

A mixture of 3-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-3-ol dihydrochloride from Example 746 (150 mg, 0.28 mmol) and DIPEA (192 μL, 1.12 mmol) in THF (3 mL) was stirred for 5 min before the addition of methanesulfonyl chloride (22 μL, 0.28 mmol). The resulting mixture was stirred at r.t. for 4 h then partitioned between H2O and DCM. The organic phase was washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%) affording 765 (67 mg, 44%). LCMS (method I): RT 3.30 min, [M+H]+ 541.2. 1H NMR (DMSO, 400 MHz): δ 8.02-8.01 (1 H, m), 7.64-7.64 (1 H, m), 7.25-7.24 (2 H, m), 6.05 (1 H, s), 4.26 (4 H, brd s), 3.96 (3 H, s), 3.78 (4 H, t, J=4.60 Hz), 3.61 (2 H, s), 3.44-3.41 (1 H, m), 3.28-3.26 (2 H, m), 3.06-3.03 (1 H, m), 2.95 (3 H, s), 2.17-2.14 (1 H, m), 2.09-1.92 (2 H, m), 1.80-1.70 (1 H, m), 1.33 (3 H, t, J=7.43 Hz)

1. customthen partitioned between H2O and DCM
2. washThe organic phase was washed with brine
3. dry with materialdried (Na2SO4)
4. concentrationconcentrated in vacuo
5. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%)