Sodium hydride → 7-Chloro-3-[(6,7-dimethoxy-quinazolin-4-ylamino)-methyl]-1-phenyl-1H-quinolin-4-one

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Reaction Steps

In a 25 mL round-bottomed flask, 6,7-dimethoxyquinazolin-4-amine (69.3 mg, 0.338 mmol) was combined with DMF (2.0 mL) to give a colorless solution. Sodium hydride (60% suspension in oil) (23.0 mg, 0.575 mmol) was added in three portions. The reaction mixture was stirred at room temperature for 15 min. After this time, the reaction mixture was a yellow solution. A DMF solution of the crude 3-bromomethyl-7-chloro-1-phenyl-1H-quinolin-4-one was next added dropwise via a syringe. The reaction mixture was stirred at 50° C. for 3 hr. After this time, TLC is quite messy, but LC/MS gives a strong peak for the desired product (approx 44%). The reaction mixture was cooled to room temperature, then was partitioned between water and ethyl acetate. The organic layer was dried over Na2SO4, filtered, then concentrated to furnish a brown oil. This crude product was dissolved in methylene chloride, then this solution was concentrated over silica gel. The silica gel-supported crude product was loaded onto a 80 gram SiliCycle column. Flash chromatography (2.5% methanol-methylene chloride ramped to 6% methanol-methylene chloride) afforded 7-chloro-3-[(6,7-dimethoxy-quinazolin-4-ylamino)-methyl]-1-phenyl-1H-quinolin-4-one. MS calcd. for C26H21ClN4O3 [(M+H)+] 472.9, obsd. 473.0.

Provenance & Evidence