反应详情

4-Amino-2-chloro-6,7-dimethoxyquinazoline (4.3 g.), 4-(2-ethoxyethoxy)piperidine (3.2 g.) and triethylamine (10 ml.) in n-butanol (400 ml.) were heated at reflux overnight under an atmosphere of nitrogen. The mixture was then cooled, evaporated in vacuo, and the residue basified (aqueous Na2CO3) and extracted 3 times with chloroform. The combined chloroform extracts were evaporated and the residue chromatographed on neutral alumina (150 g., Grade I, deactivated with 5 ml water). Elution with chloroform gave the crude product (3.6 g.) which was converted to the hydrochloride salt by treatment with hydrogen chloride in ethanol. The hydrochloride was then recrystallized from ethanol/isopropanol to give 4-amino-6,7-dimethoxy-2-[4-(2-ethoxyethoxy)piperidino]quinazoline hydrochloride (3.4 g.), m.p. 219°-220° C.

1. temperatureat reflux overnight under an atmosphere of nitrogen
2. temperatureThe mixture was then cooled
3. customevaporated in vacuo
4. extractionextracted 3 times with chloroform
5. customThe combined chloroform extracts were evaporated
6. customthe residue chromatographed on neutral alumina (150 g., Grade I, deactivated with 5 ml water)
7. washElution with chloroform
8. customgave the crude product (3.6 g.) which
9. customThe hydrochloride was then recrystallized from ethanol/isopropanol