Acryloyl chloride → N-(4-Methoxy-2-{1-methyl-3,6-dihydro-2H-pyridin-4-yl}-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide

Participants

Reaction Steps

A solution of acryloyl chloride (37 μL, 0.45 mmol) in CH2Cl2 (2.32 mL) was added dropwise over 5 minutes to 4-methoxy-6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-N′-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine (Intermediate 143, 189 mg, 0.43 mmol) in CH2Cl2 (5.8 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 0-20% CH3OH in CH2Cl2 gave the title compound (67 mg, 32%) as an pale yellow solid after trituration with diethyl ether; 1H NMR: 2.29 (3H, s), 2.36-2.41 (2H, m), 2.53-2.58 (2H, m), 2.98-3.02 (2H, m), 3.90 (3H, s), 3.91 (3H, s), 5.69-5.73 (2H, m), 6.22 (1H, dd), 6.52 (1H, dd), 6.86 (1H, s), 7.20-7.28 (3H, m), 7.52-7.55 (1H, m), 7.88 (1H, s), 8.33-8.37 (2H, m), 8.43 (1H, s), 8.45 (1H, s), 9.34 (1H, s); m/z: ES+ MH+ 495.70.

Provenance & Evidence