2-Chloro-6,7-dimethoxy-4-quinazolinamine → Terazosin

Participants

Reaction Conditions

Reaction Steps

Sixty grams (0.25 tool) of 4-amino-2-chloro-6,7-dimethoxyquinazoline and 56.8 grams (0.308 mol) of N-(2-tetrahydrofuroyl)piperazine were added to a stirred solution of 500 grams of Methyl Cellosolve® (ethylene glycol monomethyl ether). The reaction mixture was heated to and maintained at a temperature of between 115° C. to 120° C. for 8 hours, and then cooled to 60° C. The Methyl Cellosolve® was removed by vacuum distillation, the residue was taken up in 1920 ml of 45° C. distilled water, and the temperature of the solution was readjusted to 45° C. The pH was then adjusted to pH 2.5 with concentrated hydrochloric acid and the solution mixed for 1 hour. The solution was then filtered and the pH adjusted to pH 8.3 with filtered ammonia water (28%). After heating for one hour at 65° C., the solution was cooled to 15° C. and held at a temperature of between 15° -20° C. for 16 hours. The resulting crystalline product was filtered, washed with cold water (15° C.) and dried in vacuo at 65° C. to yield 90.8 grams (94%) of anhydrous base.

Provenance & Evidence