Butyronitrile → Saracatinib

Participants

Reaction Conditions

Reaction Steps

Under an atmosphere of nitrogen gas, phosphoryl chloride (0.07 ml) was added to a stirred mixture of 7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-tetrahydropyran-4-yloxy-3,4-dihydroquinazolin-4-one (0.2 g), diisopropylethylamine (0.22 ml) and butyronitrile (2 ml) that had been heated to 96° C. and the resultant mixture was heated to 96° C. for 4 hours. A second portion (0.12 ml) of phosphoryl chloride was added and the resultant mixture was heated to 96° C. for 1.7 hours. 6-Chloro-2,3-methylenedioxyaniline (0.098 g) was added and the resultant mixture was heated to 96° C. for 2 hours. The mixture was allowed to cool to ambient temperature. Water (2 ml) was added and the organic layer was separated. The aqueous layer was washed with butyronitrile (1 ml). The aqueous layer was basified to pH9 by the addition of concentrated aqueous sodium hydroxide solution (47% w/w) and extracted with n-butanol (2×2 ml). The resultant organic layers were combined and evaporated. There was thus obtained 4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-tetrahydropyran-4-yloxyquinazoline (0.094 g).

Provenance & Evidence