反应详情

A solution of acryloyl chloride (22.5 mg, 0.25 mmol) in CH2Cl2 (1 mL) was added dropwise to a stirred solution of 4-(3-dimethylaminoazetidin-1-yl)-6-methoxy-N-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine (Intermediate 139, 108 mg, 0.25 mmol) in CH2Cl2 (12 mL), which was cooled in an ice/water bath. The solution was stirred for 10 minutes while being cooled by the bath, was then allowed to warm to r.t. and was then stirred for 1 h. The mixture was then diluted with CH2Cl2 and washed with sat. NaHCO3, brine and was then dried (MgSO4). Purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 gave the title compound (56 mg, 46%) as a brown solid after trituration with diethyl ether; 1H NMR: 1.75-1.82 (2H, m), 1.90-1.97 (2H, m), 2.08 (6H, s), 2.98-3.09 (3H, m), 3.54 (2H, t), 3.85 (3H, s), 3.93 (2H, t), 4.09 (2H, t), 5.69 (1H, dd), 6.18-6.25 (2H, m), 6.49 (1H, dd), 6.95 (1H, d), 7.70 (1H, s), 7.89 (1H, s), 8.03 (1H, s), 8.26 (1H, d), 9.24 (1H, s); m/z: ES+ MH+ 489.63.

1. temperaturewas cooled in an ice/water bath
2. temperaturewhile being cooled by the bath
3. stirringwas then stirred for 1 h
4. washwashed with sat. NaHCO3, brine
5. dry with materialwas then dried (MgSO4)
6. customPurification by FCC
7. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2