Acetic Anhydride → HCID 10072170, compound

Participants

Reaction Steps

A solution of acetic anhydride (42 μl) in methylene chloride (5 ml) was added dropwise to a stirred solution of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(3S)-piperidin-3-yloxy]quinazoline hydrochloride (0.175 g, 0.4 mmol; prepared as described in Example 49) and diisopropylethylamine (208 μl) in methylene chloride (20 ml) at 0° C. and the mixture was stirred for 2 hours and allowed to warm to room temperature. The reaction mixture was washed with saturated sodium bicarbonate solution, dried (MgSO4), filtered and evaporated to give a white foam. This was purified by column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5). The fractions containing the desired product were combined and evaporated under vacuum to give the title product as a colourless foam (0.117 g, 66%); 1H NMR Spectrum: (DMSO d6 at 373K) 1.40-1.65 (m, 1H), 1.70-1.94 (m, 2H), 2.00 (s, 3H), 1.95-2.20 (m, 1H), 3.20-3.70 (m, 3H), 3.70-4.10 (m, 1H), 3.95 (s, 3H), 4.40-4.70 (m, 1H), 7.15-7.33 (m, 2H), 7.33-7.50 (m, 1H), 7.50-7.70 (m, 7.90 (s, 1H), 8.40 (s, 1H), 9.25 (s, 1H); Mass Spectrum: (M+H)+ 445.

Provenance & Evidence