Dimethylsulphamoyl chloride → HCID 60036681, compound

Participants

Reaction Steps

4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(3S)-pyrrolidin-3-yloxy]quinazoline hydrochloride (0.21 g, 0.49 mmole; prepared as described in Example 30-preparation of starting materials) was dissolved in a mixture of methylene chloride (4 ml), pyridine (1 ml) and di-isopropylethyl amine (0.17 ml) under a nitrogen atmosphere. Dimethylsulfamoyl chloride (0.08 ml, 0.75 mmole) was added to the stirred solution. After stirring overnight at ambient temperature, the reaction mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic layer was washed with 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 evaporated under vacuum and the residual gum was triturated with diethylether and evaporated to give the title product as a dry foam (0.13 g; 53%); 1H NMR Spectrum: (DMSO d6) 2.16-2.21 (m, 1H); 2.25-2.38 (m, 1H); 2.76 (s, 6H); 3.41-3.50 (m, 3H); 3.71 (dd, 1H); 3.93 (m, 3H); 5.18 (m, 1H); 7.15-7.35 (m, 2H); 7.44-7.55 (m, 2H); 7.78 (s, 1H); 8.37 (s, 1H); 9.59 (s, 1H); Mass Spectrum: (M+H) 496.

Provenance & Evidence