反应详情

A solution of acryloyl chloride (0.092 mL, 1.14 mmol) in CH2Cl2 (1 mL) was added dropwise to a mixture of N′-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-4-methoxy-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine (Intermediate 63, 480 mg, 1.03 mmol) and DIPEA (0.214 mL, 1.24 mmol) in CH2Cl2 (18 mL) at r.t. After 0.25 h, additional acrolyl chloride (15 mg in 0.15 mL CH2Cl2) was added. The mixture was stirred for 0.5 h and then washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification by FCC, eluting with 2.5% 7N methanolic ammonia in CH2Cl2 gave the title compound (390 mg, 73%) as a yellow solid, after trituration with CH3OH; 1H NMR: 2.27 (3H, s), 2.53-2.61 (4H, m), 2.84-2.97 (4H, m), 3.77 (3H, s), 5.70 (1H, d), 6.17 (1H, d), 6.61 (1H, dd), 6.89 (1H, s), 7.11 (1H, t), 7.3-7.42 (1H, m), 8.10 (1H, s), 8.26-8.47 (2H, m), 8.70 (1H, s), 8.83 (1H, d), 8.96 (1H, s), 9.02 (1H, s); m/z: ES+ MH+ 519.

1. washwashed with brine
2. dry with materialdried (Na2SO4)
3. concentrationconcentrated in vacuo
4. customPurification by FCC
5. washeluting with 2.5% 7N methanolic ammonia in CH2Cl2