Thionyl Chloride → HCID 20351340, compound

Participants

Reaction Steps

A solution of 6-methoxy-1,4-benzodioxan-2-carbonyl chloride (2.17 g.) (prepared from the acid and thionyl chloride) in dichloromethane (25 ml.) was added dropwise to a stirred suspension of 4-amino-2-piperazin-1-yl-6,7-dimethoxy-quinazoline (2.48 g.) in methylene chloride (50 ml.) at room temperature. After the addition was complete, the mixture was stirred at room temperature for 4 hours, then filtered and the solid suspended in aqueous potassium carbonate solution and extracted with chloroform. The combined extracts were washed with water, dried (Na2SO4) and evaporated in vacuo to leave a solid residue (4.15 g.) which was chromatographed on silica (160 g.) and eluted with chloroform then chloroform-methanol (2.5%). Similar fractions (t.l.c.) were combined, evaporated in vacuo then the residue taken up in ethyl acetate-methanol and treated with ethereal hydrogen chloride. Addition of further ether followed by cooling yielded a solid which was collected and recrystallized from methanol to give 4-amino-2-[4-(6-methoxy-1,4-benzodioxan-2-carbonyl)piperazin-1-yl-]-6,7-dimethoxyquinazoline hydrochloride hydrate (0.95 g.), m.p. 220°-222° C.

Provenance & Evidence