Dimethylformamide → 4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazoline-6-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

A high pressure vessel was charged with 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl trifluoromethanesulfonate (10 g, 22.1 mmol), palladium (II) acetate (700 mg, 3.12 mmol), triethylamine (7.6 ml, 54.5 mmol), 1,3-bis diphenylphosphinopropane (1.46 g, 3.54 mmol), trioctylsilane (13.2 ml, 29.4 mmol) and N,N-dimethylformamide (110 ml). The reaction mixture was heated at 70° C. under a carbon monoxide atmosphere (13 Bar) for 3 hours. The mixture was cooled and the lower N,N-dimethylformamide layer was separated, filtered and concentrated under reduced pressure. The residue was suspended in methanol, filtered, washed with isohexane and dried to give 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazoline-6-carbaldehyde (3.0 g, 41%) as a pale orange solid; 1H NMR spectrum: (DMSO d6) 4.07 (s, 3H), 7.29 (t, 1H), 7.36 (s, 1H), 7.51 (t, 2H), 8.52 (s, 1H), 8.95 (s, 1H), 10.36 (s, 1H), 10.45 (s, 1H); Mass Spectrum: (M+H)+ 332.

Provenance & Evidence