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

Temperature

60 °C

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.

1. temperatureThe reaction mixture was heated to and
2. temperaturemaintained at a temperature of between 115° C. to 120° C. for 8 hours
3. customThe Methyl Cellosolve® was removed by vacuum distillation
4. customwas taken up in 1920 ml of 45° C.
5. distillationdistilled water
6. customwas readjusted to 45° C
7. additionthe solution mixed for 1 hour
8. filtrationThe solution was then filtered
9. temperatureAfter heating for one hour at 65° C.
10. temperaturethe solution was cooled to 15° C.
11. filtrationThe resulting crystalline product was filtered
12. washwashed with cold water (15° C.)
13. customdried in vacuo at 65° C.

ORD record

ord-1f52a7b0e9894befabc2bc5d6570a2ea

Source dataset

uspto-grants-1996_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05504207