Dimethylformamide → HCID 68523595, compound

Participants

Reaction Steps

4-(3-chloro-2-fluoroanilino)-6-hydroxy-7-methoxyquinazoline (prepared as described in the starting materials used in Example 22; 4.0 g, 12.5 mmol) was mixed with tert-butyl (3S)-3-[(4-nitrophenyl)sulfonyloxy]pyrrolidine-1-carboxylate (4.7 g, 12.6 mmol) and cesium fluoride (5.7 g, 7.5 mmol). Dry N,N-dimethylformamide (60 ml) was then added and the mixture stirred at ambient temperature overnight. The mixture was diluted with ethyl acetate and filtered. The filtrate was washed with water, 50% aqueous brine then brine, dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (98/2). The fractions containing the expected product were combined and evaporated to give 4-(3-chloro-2-fluoroanilino)-6-[(3R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yloxy]-7-methoxyquinazoline as a dry foam (2.35 g, 38%); 1H NMR Spectrum: (DMSO d6) 1.39 (s, 9H); 2.10-2.30 (m, 2H); 3.35-3.50 (m, 3H); 3.64-3.71 (m, 1H); 3.92 (s, 3H); 5.12 (m, 1H); 7.21 (s, 1H); 7.23-7.27 (m, 1H); 7.44-7.55 (m, 2H); 7.80 (s, 1H); 8.37 (s, 1H); 9.61 (s, 1H); Mass Spectrum: (M+H)+ 489.

Provenance & Evidence