Hydrochloric Acid → HCID 68908613, compound

Participants

Reaction Conditions

Reaction Steps

4.0M HCl in dioxane (6.0 ml) was added to a stirred suspension of tert-butyl (3S)-3-[(4-chloro-6-methoxyquinazolin-7-yl)oxy]piperidine-1-carboxylate (3.21 g) and 3-chloro-2-fluoroaniline (0.98 ml) in acetonitrile (50 mL). The reaction mixture was heated at 80° C. and left at this temperature overnight. The solvent was evaporated and the residue purified by flash column chromatography eluting with increasingly polar mixtures of methylene chloride/7N ammonia solution in methanol (97/3 to 95/5) to give N-(3-chloro-2-fluorophenyl)-6-methoxy-7-[(3S)-piperidin-3-yloxy]quinazolin-4-amine dihydrochloride as a solid (3.20 g); 1H NMR Spectrum: (DMSO d6) 1.56 (m, 2H), 1.72 (m, 1H), 2.12 (m, 1H), 2.48-2.59 (m, 2H), 2.82 (m,1H), 3.20 (m, 1H), 3.95 (s, 3H), 4.49 (m, 1H), 7.26 (s, 1H), 7.28 (m, 1H), 7.47 (m, 1H), 7.53 (m, 1H), 7.81 (s, 1H), 8.38 (s, 1H), 9.63(s, 1H); Mass Spectrum: (M+H)+ 403.

Provenance & Evidence