反应详情

温度

60 °C

Triethylamine (42.2 mg, 0.417 mmol) and Ac2O (0.013 mL, 0.139 mmol) were added to a stirred solution of N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-(piperazin-1-ylmethyl)pyridin-2-amine (60 mg, 0.139 mmol) in DCM (3 mL, 46.6 mmol) and DMF (0.5 mL, to improve solubility) at room temperature. The mixture was stirred for 1 h and then diluted with NH4Cl(aq), water (10 mL) and EtOAc (10 mL each). The separated aqueous layer was extracted with EtOAc (3×15 mL) and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The residue was heated at 60° C. with excess of Na2CO3 (50 mg) in CH3CN (5 mL) and water (1 mL) for 2 h. The resulting suspension was concentrated and washed with a minimal amount of cold MeOH to give 1-(4-((6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9H-purin-6-yl)pyridin-3-yl)methyl)piperazin-1-yl)ethanone (37 mg, 56%) as a yellow solid. LCMS (API-ES) m/z 474 (M+H)+; 1H NMR (400 MHz, d6-DMSO) δ 13.63 (br. s., 1H) 12.64 (br. s., 1H) 9.73 (br. s., 1H) 8.60 (s, 1H) 8.54 (br s., 1H) 8.03-8.30 (m, 2H) 6.85 (d, J=8.61 Hz, 1H) 3.85 (s, 3H) 3.53 (br. s., 2H) 3.39-3.49 (m, 4H) 2.85 (s, 3H) 2.25-2.46 (m, 4H) 1.97 (s, 3H).

1. extractionThe separated aqueous layer was extracted with EtOAc (3×15 mL)
2. washthe combined organic layers were washed with brine
3. dry with materialdried over Na2SO4
4. concentrationconcentrated
5. concentrationThe resulting suspension was concentrated
6. washwashed with a minimal amount of cold MeOH