Cesium fluoride → HCID 60036687, compound

Participants

Reaction Steps

Dimethylformamide (8 ml) was added to 4-(3-chloro-2-fluoroanilino)-6-hydroxy-7-methoxyquinazoline (0.489 g; prepared as described in the starting materials for Example 22), (2S,4R)-1-(tert-butoxycarbonyl)-2-(N,N-dimethylcarbamoyl)-4-[(4-nitrophenyl)sulfonyloxy]pyrrolidine (0.678 g) and cesium fluoride (0.697 g). The reaction mixture was then stirred at room temperature for 16 hours. The reaction mixture was evaporated under vacuum and the residue dissolved in methylene chloride/methanol and adsorbed onto silica. The product was then purified by column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10). The fractions containing the expected product were combined and evaporated. The residue was re-purified by column chromatography eluting with increasingly polar mixtures of ethyl acetate/methanol (100/0 to 92/8). The fractions containing the required product were combined and evaporated under vacuum to give 4-(3-chloro-2-fluoroanilino)-6-[(2S,4S)-1-(tert-butoxycarbonyl)-2-(N,N-dimethylcarbamoyl)pyrrolidin-4-yloxy]-7-methoxyquinazoline as a colourless gum which crystallised on standing (0.36 g); 1H NMR Spectrum: (DMSO d6 @ 373K) 1.41 (s, 9H), 1.99 (m, 1H), 2.92-3.03 (m, 7H); 3.44 (m, 1H), 3.96 (s 3H), 4.14 (m, 1H), 4.70 (t, 1H), 5.10 (m, 1H), 7.22-7.30 (m, 2H), 7.44 (t, 1H), 7.62 (t, 1H), 7.84 (s, 1H), 8.40 (s, 1H), 9.30 (s, 1H); Mass Spectrum: (M+H)+ 560.

Provenance & Evidence