反应详情

温度

0 °C

The crude residue from Step 1 was taken up in DCM (3 mL, 46.6 mmol), cooled to 0° C. and then DIEA (0.132 mL, 0.755 mmol) and methanesulfonyl chloride (0.029 mL, 0.378 mmol) were added. The mixture was stirred at the same temperature for 1 h and then diluted with NH4Cl(aq) and water (10 mL each) and diluted with DCM (10 mL). The separated aqueous layer was extracted with DCM (2×15 mL) and the combined organic layers were washed with brine, dried over Na2SO4, concentrated and chromatographed through a Redi-Sep pre-packed silica gel column (DCM to 10% MeOH in DCM) to give N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-amine (21 mg, 16%) as a yellow solid. LCMS (API-ES) m/z 510 (M+H)+; 1H NMR (400 MHz, d6-DMSO) δ 13.58 (br. s., 1H) 12.62 (br. s., 1H) 9.73 (br. s., 1H) 8.62 (s, 1H) 8.54 (d, J=2.54 Hz, 1H) 8.22 (d, J=1.56 Hz, 1H) 8.18 (dd, J=8.90, 2.45 Hz, 1H) 6.85 (d, J=8.80 Hz, 1H) 3.85 (s, 3H) 3.56 (s, 2H) 3.01-3.18 (m, 4H) 2.86 (s, 3H) 2.86 (s, 3H) 2.53 (br. s., 4H).

1. extractionThe separated aqueous layer was extracted with DCM (2×15 mL)
2. washthe combined organic layers were washed with brine
3. dry with materialdried over Na2SO4
4. concentrationconcentrated
5. customchromatographed through a Redi-Sep pre-packed silica gel column (DCM to 10% MeOH in DCM)