Iodine → HCID 136346625, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-amino-5-methylbenzamide (1.0 g, 6.7 mmol), 4-fluorobenzaldehyde (0.83 g, 6.7 mmol), iodine (2.03 g, 8.0 mmol), and potassium carbonate (1.38 g, 10 mmol) in DMF (50 mL) was stirred at 80° C. for 16 hours. The reaction mixture was cooled to 20° C. and poured into icy water. The solid was collected by filtration, washed with water, and air dried to give 2-(4-fluoro-phenyl)-6-methyl-3H-quinazolin-4-one (1.41 g, 83%). A solution of 2-(4-fluoro-phenyl)-6-methyl-3H-quinazolin-4-one (1.4 g, 5.5 mmol), NBS (0.98 g, 5.6 mmol), and benzoyl peroxide (67.0 mg, 0.276 mmol) in AcOH (150 mL) and chloroform (150 mL) was stirred at 80° C. for 5 hours with light shedding on. The reaction mixture was cooled to 20° C. and concentrated using a rotary evaporator to yield the crude bromide. A solution of the above crude bromide in DMF (20 mL) and 1,4-dioxane (100 mL) was mixed with morpholine (10 mL) and stirred at 80° C. for 4 hours. The reaction was quenched by adding water (200 mL), extracted with dichloromethane (3×100 mL), and concentrated using a rotary evaporator. The residue was further purified by column (SiO2, Hexanes/EtOAc/MeOH=4:3:1) to yield 2-4-fluoro-phenyl)-6-morpholin-4-ylmethyl-3H-quinazolin-4-one (0.89 g, 48% over two steps). A solution of 2-(4-fluoro-phenyl)-6-morpholin-4-ylmethyl-3H-quinazolin-4-one (0.89 g, 2.62 mmol) in dichloromethane (100 mL) and MeOH (50 mL) was mixed with HCl in ether (8 mL, 16 mmol) and stirred for 1 hour. The reaction was concentrated using a rotary evaporator. The solid was rinsed with DCM (50 mL) and MeOH (5 mL), collected by filtration, washed with DCM-MeOH (10:1) to afford 2-(4-fluorophenyl)-6-(morpholinomethyl)quinazolin-4(3H)-one (0.82 g, 76%) as an off-white solid; MS (ES) m/z: 340 (M+1); MP 321.8-323.3° C.

Provenance & Evidence