Hydrochloric Acid → HCID 11612313, compound

Participants

Reaction Steps

4M Hydrogen chloride (7.5 ml) in dioxane was added to a stirred solution of (1) tert-butyl (2R,4R)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-2-[(methylamino)carbonyl]piperidine-1-carboxylate (4.17 g) in acetonitrile (10 ml) and stirred for 2 hours at room temperature. A second portion of 4M Hydrogen chloride (3.75 ml) in dioxane was added and the mixture stirred a further 1½ hours. The reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organics were washed with brine, dried (Na2SO4), filtered and evaporated. The residues were purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (96/4). The fractions containing the desired product were combined and evaporated. The resulting solids were triturated with iso-hexane/methylene chloride filtered and dried under high vacuum at 50° C. to give the title product as a white solid (1.94 g, 57%); 1H NMR Spectrum: (DMSO d6) 1.67-1.82 (m, 2H); 1.83-1.94 (m, 1H); 1.98-2.08 (m, 1H); 2.59 (d, 3H); 2.74-2.83 (m, 1H); 2.90-3.01 (m, 1H); 3.48-3.55 (m, 1H); 3.94 (s, 3H); 4.83 (br s, 1H); 7.22 (s, 1H); 7.23-7.30 (m, 1H); 7.43-7.57 (m, 2H); 7.75-7.81 (m, 1H); 7.84 (s, 1H); 8.37 (s, 1H); 9.52 (s, 1H); Mass Spectrum: (M+H)+ 460.

Provenance & Evidence