1,2-Dichloroethane → HCID 86593649, compound

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Reaction Steps

Formula I where R1, R2, R4, R6, R7, R8 and R9 are H; R3 is Chloro; R5 is Benzyl, R10 is Benzyl; and V is CR′R″ where R′ and R″ are H: To a solution of 2-[(1-benzyl-6-oxo-piperidine-2-carbonyl)-amino]-4-chloro-benzoic acid (165 mg, 0.427 mmol) in 5 mL of DMF was added EDC (245 mg, 1.28 mmol) and the mixture stirred at room temperature. After 1 hour, benzylamine (140 μL, 1.28 mmol) was added, and the reaction mixture was stirred at room temperature for an additional 3 hours. After evaporating the solvents, the residue was dissolved in 100 mL of DCM, and washed with saturated sodium bicarbonate and brine. The organic layer was dried over sodium sulfate and filtered. The solvent was removed to afford crude 1-benzyl-6-oxo-piperidine-2-carboxylic acid (2-benzylcarbamoyl-5-chloro-phenyl)-amide, a compound of Formula 402. This was dried under vacuum and then added to a mixture of 10 mL of ethylene glycol and sodium hydroxide (17 mg, 0.425 mmol), followed by stirring at 130° C. for two days with monitoring by LC-MS. The mixture was then poured into 100 mL of water. After extraction with DCM, the resulting crude product was purified over silica gel (stepwise gradient 1:4, 1:2, 1:1, 2:1, 4:1 with ethyl acetate:hexanes as eluent) to give the desired pure product of Formula I, 3-benzyl-2-(1-benzyl-6-oxo-piperidin-2-yl)-7-chloro-3H-quinazolin-4-one (20 mg, 10%).

Provenance & Evidence