4-Chloro-8-methylquinazoline → 8-Methylquinazoline

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 4-Chloro-8-methylquinazoline (45 g, 0.252 mol) in DCM (700 mL) under N2 was added p-toluenesulfonylhydrazide (65.9 g, 0.353 mol) in portions. The reaction mixture was heated at 45° C. for 12 h. The reaction completion was monitored by LCMS and TLC. After completion, the reaction mixture was cooled to RT, the solvent evaporated to dryness and the resulted residue redissolved in EtOH (500 mL) and added 2N NaOH solution (300 mL) and refluxed for 6 h. After confirming by LCMS, the reaction mixture was cooled to RT and extracted with MTBE (3×600 mL). The combined organic layers were washed with brine solution, dried over sodium sulfate and concentrated under vacuum. The resulted residue was filtered through column chromatography using neutralized silica gel (60-120 mesh) and pet ether/ethyl acetate as an elutent to yield (15 g, 27% yield) of the titled compound as a low melting yellow solid. 1H NMR (DMSO-d6, 400 MHz) δ 9.54 (s, 1H), 9.31 (s, 1H), 7.97-7.94 (dd, J=8.8, 8.1 Hz, 1H), 7.87-7.84 (m, 1H), 7.65-7.62 (d, J=15.2 Hz, 1H), 2.67 (s, 3H).

Provenance & Evidence