Thionyl Chloride → HCID 68930213, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of N-(5-hydroxymethyl-2-methylphenyl)-4-(4-phenylquinazolin-2-ylamino)benzamide (1.88 g, 4.08 mmol) in dichloromethane (50 mL) that had been cooled to 0° C. in an ice bath was added slowly thionyl chloride (475 μL, 6.54 mmol), and the mixture was stirred at 0° C. for 2 h. Excess thionyl chloride and dichloromethane were removed on a rotary evaporator. The residue was stirred with ether, filtered, washed with ether, and dried to give N-(5-chloromethyl-2-methylphenyl)-4-(4-phenylquinazolin-2-ylamino)benzamide as a yellow solid (2.15 g, 100%). This material was then added to a 1.6 M solution of methylamine in tetrahydrofuran (20 mL, 32 mmol) that had been cooled to 0° C. in an ice bath. The stirred mixture was allowed to warm to rt overnight and then was concentrated on a rotary evaporator. The residue was redissolved in dichloromethane, washed with saturated sodium bicarbonate and dried over sodium sulfate. The solvent was then removed on a rotary evaporator and the residue purified by flash column chromatography to give N-{2-methyl-5-[(methylamino)methyl]-phenyl}-4-[(4-phenylquinazolin-2-yl)amino]benzamide (1.12 g, 57%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 10.33 (s, 1H), 9.71 (s, 1H), 8.17 (d, 2H), 8.00 (d, 2H), 7.89-7.79 (m, 5H), 7.65 (m, 3H), 7.42 (m, 1H), 7.34 (s, 1H), 7.21 (d, 1H), 7.12 (d, 1H), 3.65 (s, 2H), 2.28 (s, 3H), 2.23 (s, 3H). MS (EI) for C30H27N5O: 474.2 (MH+).

Provenance & Evidence