Acryloyl chloride → HCID 86677290, compound

Participants

Reaction Steps

A solution of acryloyl chloride (0.354 mL, 4.35 mmol) in CH2Cl2 (5 mL) was added dropwise to a mixture of N1-(2-dimethylaminoethyl)-5-methoxy-N1-methyl-N4-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,2,4-triamine (Intermediate 125, 1.9 g, 4.35 mmol) in CH2Cl2 (100 mL), which was cooled in an ice/water bath. The resulting mixture was stirred for 1 h and then washed with sat. NaHCO3. The resulting organic solution was dried (Na2SO4) and concentrated in vacuo. Purification by FCC, eluting with 1.5% 7N methanolic ammonia in CH2Cl2 gave the title compound (1.069 g, 50%) as an oil which crystallised on standing to give a cream crystalline solid. Some later fractions from the FCC which had a brown colour were concentrated and re-chromatographed to give more of the title compound (334 mg, 16%) as a pale brown oil which crystallised on standing to give a tan-coloured crystalline solid. Total yield: 1.403 g, 66%; 1H NMR: 1.69-1.77 (2H, m), 1.88-1.97 (2H, m), 2.21 (6H, s), 2.29 (2H, t), 2.71 (3H, s), 2.88 (2H, t), 3.02 (2H, t), 3.84 (3H, s), 4.09 (2H, t), 5.74 (1H, dd), 6.24 (1H, dd), 6.40 (1H, dd), 6.97-7.02 (2H, m), 7.87 (1H, s), 8.13 (1H, s), 8.31 (1H, d), 8.85 (1H, s), 10.08 (1H, s); m/z: ES+ MH+ 491.34.

Provenance & Evidence