Methanesulfonyl chloride → HCID 9982010, compound

Participants

Reaction Steps

4-(3-chloro-2-fluoroanilino)-6-[(3R)-pyrrolidin-3-yloxy]-7-methoxyquinazoline hydrochloride (0.21 g, 0.49 mmole) was dissolved in a mixture of dichloromethane (4 ml), pyridine (1 ml) and diisopropylethylamine (0.17 ml) under a nitrogen atmosphere. Methanesulfonyl chloride (0.06 ml, 0.07 mmol) was added to the stirred solution. After stirring 2 hours at room temperature, the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (96/4). The fractions containing the expected product were combined and evaporated under vacuum and the residual gum was triturated with diethylether, filtered and dried under vacuum to give the title product as a white solid (0.17 g, 74%); 1H NMR Spectrum: (DMSO d6) 2.18-2.37 (m, 2H); 2.93 (s, 3H); 3.33-3.45 (m, 2H); 3.5 (d, 1H); 3.69 (dd, 1H); 3.92 (s, 3H); 5.17 (m, 1H); 7.15-7.35 (m, 2H); 7.40-7.60 (m, 2H); 7.5 (m, 2H); 7.80 (s, 1H); 8.37 (s, 1H); 9.6 (s, 1H); Mass Spectrum: (M+H)+ 467.

Provenance & Evidence