Triethylamine → 5-chloro-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [5-(5-chloro-2-difluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-amide

Participants

Reaction Steps

A mixture of 5-chloro-pyrazolo[1,5-a]pyrimidine-3-carbonyl chloride (500 mg, 2.3 mmol) (prepared according to the procedure in Journal of Medicinal Chemistry, 55(22), 10090-10107; 2012) and 5-(5-chloro-2-difluoromethoxyphenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-ylamine (868 mg, 2.3 mmol) were suspended in triethylamine (0.35 mL, 2.5 mmol) and DCM (10 mL) and the mixture was left to stir at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane and the resultant organic layer was washed with saturated aqueous sodium hydrogen carbonate solution, and brine, dried (Na2SO4) and evaporated to afford an oil. The resultant oil was purified by flash chromatography on silica eluting with 0-2% MeOH in DCM. Collecting appropriate fractions, followed by evaporation gave 5-chloro-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [5-(5-chloro-2-difluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-amide as a brown oil (1.19 g, 91%). 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.07 (s, 1H), 8.72 (s, 1H), 8.67 (d, 1H, J=7.3 Hz), 8.38 (s, 1H), 7.60 (d, 1H, J=2.3 Hz), 7.51 (dd, 1H, J=2.6, 8.8 Hz), 7.38 (d, 1H, J=8.9 Hz), 6.95 (d, 1H, J=7.2 Hz), 6.43 (t, 1H, J=72.8 Hz), 5.41 (d, 1H, J=10.9 Hz), 5.31 (d, 1H, J=11.0 Hz), 3.76-3.49 (m, 2H), 1.27 (s, 1H), 0.94-0.84 (m, 2H), 0.00 (s, 9H).

Provenance & Evidence