Bromomethylcyclopropane → 4-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-1-(cyclopropylmethyl)piperidine-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

DIPEA (0.068 g, 0.522 mmol) and cyclopropylmethylbromide (0.035 g, 0.260 mmol) were added to a stirred solution of 4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-c arboxamide hydrochloride (0.10 g, 0.172 mmol) in dimethylformamide (1 ml). The reaction mixture was heated at 100° C. for 5 hours, cooled to room temperature and purified by preparative LCMS (standard acidic system) to give the title product (0.0253 g, 27.8%) as a white solid; 1H NMR Spectrum: (DMSO-d6) 0.00 (m, 2H), 0.41 (m, 2H), 0.76 (m, 1H), 1.77 (m, 2H), 2.03-2.13 (m, 7H), 2.81 (m, 2H), 3.32 (m, 2H), 3.61 (s, 2H), 3.91 (s, 3H), 7.06 (s, 1H), 7.14 (s, 2H), 7.26 (t, 1H), 7.47-7.53 (m, 2H), 8.32 (s, 1H), 8.38 (s, 1H), 9.70 (s, 1H); Mass Spectrum: (M+H)+ 527.

Provenance & Evidence