Acryloyl chloride → N-{2-[(3R)-3-Dimethylaminopyrrolidin-1-yl]-4-methoxy-5-[(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]phenyl}prop-2-enamide

Participants

Reaction Steps

A solution of acryloyl chloride (64 μL, 0.79 mmol) in CH2Cl2 (4 mL) was added dropwise over 10 minutes to 4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-6-methoxy-N-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine (Intermediate 153, 336 mg, 0.76 mmol) in CH2Cl2 (11 mL), which was cooled in an ice/CH3OH bath. The mixture was stirred for 0.5 h, and was then diluted with 10% CH3OH/CH2Cl2. The resulting solution was washed with sat.NaHCO3, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-5% methanolic ammonia in CH2Cl2 gave the title compound (296 mg, 79%) as an orange solid after trituration with diethyl ether; 1H NMR: 1.70-1.81 (1H, m), 2.05-2.13 (1H, m), 2.18 (6H, s), 2.68-2.76 (1H, m), 3.17-3.27 (3H, m), 3.35-3.42 (1H, m), 3.84 (3H, s), 5.67 (1H, dd), 6.17 (1H, dd), 6.51 (1H, dd), 6.56 (1H, s), 7.05 (1H, dd), 7.21 (1H, d), 7.40-7.45 (1H, m), 7.84 (1H, s), 8.02 (1H, s), 8.30 (1H, d), 8.46 (1H, d), 8.76 (1H, s), 8.78 (1H, d), 9.35 (1H, s); m/z: ES+ MH+ 499.69.

Provenance & Evidence