Formaldehyde → HCID 59371213, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 4-(3-chloro-2-fluoroanilino)-6-[(2S,4R)-1-(tert-butoxycarbonyl)-2-(methoxycarbonyl)pyrrolidin-4-yloxy]-7-methoxyquinazoline (480 mg, 0.88 mmol) in formic acid (50 ml) was reacted with paraformaldehyde (29 mg, 0.97 mmol) and the resulting mixture heated at 85° C. for 6 hours. The reaction mixture was evaporated and the residues partitioned between saturated aqueous NaHCO3 (50 ml) and ethyl acetate (100 ml). The organic layer was dried over MgSO4, filtered and evaporated. The residue was purified by flash chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10). The fractions containing the expected product were combined and evaporated to give 4-(3-chloro-2-fluoroanilino)-6-[(2RS,4R)-1-methyl-2-(methoxycarbonyl)pyrrolidin-4-yloxy]-7-methoxyquinazoline as a white foam (265 mg); Mass Spectrum: (M+H)+ 461.

Provenance & Evidence