反应详情

温度

-5 °C

A solution of acryloyl chloride (0.604 mL, 1M in CH2Cl2, 0.60 mmol) was added dropwise to 4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-N-[4-(1H-indol-3-yl)pyrimidin-2-yl]-6-methoxybenzene-1,3-diamine (Intermediate 164, 268 mg, 0.60 mmol) in CH2Cl2 (10 mL) and 10 mL DMA, which was cooled to −5° C. The resulting mixture was stirred at −5° C. for 1 h and was then diluted with CH2Cl2 (100 mL). The resulting solution was washed with sat. NaHCO3 (25 mL), water (25 mL), and then sat. brine (4×25 mL), and was then concentrated in vacuo. Purification by FCC, eluting with 0-30% CH3OH in CH2Cl2 gave the title compound (135 mg, 45%) as a beige solid; 1H NMR (CDCl3) 1.98 (1H, s), 2.18 (1H, d), 2.94 (1H, s), 3.11 (4H, d), 3.88 (3H, s), 5.73 (1H, d), 6.40 (2H, d), 6.76 (1H, s), 7.17 (1H, d), 7.22-7.24 (1H, m), 7.41-7.46 (1H, m), 7.62 (1H, s), 8.16 (1H, s), 8.39 (1H, d), 8.45 (1H, s), 8.75 (1H, s), 8.86 (1H, s), 9.56 (1H, s); m/z: ES+ MH+ 498.

1. washThe resulting solution was washed with sat. NaHCO3 (25 mL), water (25 mL)
2. concentrationsat. brine (4×25 mL), and was then concentrated in vacuo
3. customPurification by FCC
4. washeluting with 0-30% CH3OH in CH2Cl2