Hydrochloric Acid → Cxd-101

Participants

Reaction Steps

tert-Butyl (2-{[4-(1-{1,3-dimethyl-1H-pyrazol-4-ylmethyl}piperidin-4-yl)benzoyl]amino}phenyl)carbamate (Method 6 below; 92.3 g, 183.3 mmol) was slurried in methanol (754 ml) and water (141 ml) and cooled to 0-5° C. Concentrated hydrochloric acid was added maintaining the temperature below 20° C. The reaction mixture was stirred for 20 hours at ambient temperature. The reaction was cooled to 0-5° C. and aqueous sodium hydroxide solution added maintaining the temperature at below 20° C. until a pH of 12-14 is obtained. The reaction mixture was heated to reflux temperature for 30 minutes before cooling to 20° C. over about 4 hours. The product was collected by filtration and washed with aqueous methanol before being dried in vacuo at 45° C. to constant weight to give the title compound (63.3 g 86%).

Provenance & Evidence