Cesium fluoride → HCID 68523549, compound

Participants

Reaction Steps

A mixture of 4-(3-chloro-2-fluoroanilino)-6-hydroxy-7-methoxyquinazoline (2.0 g; prepared as described in Example 22-preparation of starting materials), tert-butyl-3-(R)-[(4-nitrophenyl)sulfonyloxy]pyrrolidine-1-carboxylate (2.4 g) and cesium fluoride (2.9 g) in dimethylformamide (30 ml) was stirred at room temperature for 18 hours. The reaction mixture was evaporated under vacuum and partitioned between methylene chloride and water. The solutions were filtered to remove insoluble solids and the methylene chloride was washed with water, saturated brine and adsorbed onto silica. The product was then purified by column chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (saturated with ammonia) (100/0 to 96/4). The fractions containing the required product were combined and evaporated under vacuum to give 4-(3-chloro-2-fluoroanilino)-6-[(3S)-1-tert-butoxycarbonylpyrrolidin-3-yloxy]-7-methoxyquinazoline as a yellow foam (2.9 g, 95%); 1H NMR Spectrum: (DMSO-d6) 1.40 (s, 9H), 2.00-2.32 (m, 2H), 3.20-3.55 (m, 3H), 3.69 (dd, 1H), 3.92 (s, 3H), 5.00-5.20 (m, 1H), 7.20 (s, 1H), 7.20-7.32 (m, 1H), 7.40-7.57 (m, 2H), 7.80 (s, 1H), 8.37 (s, 1H), 9.60 (s, 1H); Mass Spectrum: (M+H)+ 489.

Provenance & Evidence