反应详情

A solution of 5-bromo-1-(3-fluoro-benzyl)-3-methyl-3,4-dihydro-1H-quinazolin-2-one (156 mg, 0.45 mmol) and 1-Boc-piperazine (100 mg, 0.54 mmol) in 1 ml toluene was added to a mixture of Pd2(dba)3 (8 mg, 0.009 mmol), BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (14 mg, 0.022 mmol), and NaOt-Bu (65 mg, 0.67 mmol). With stirring, the solution was heated at 95° C.–100° C. for 1 hour and was allowed to cool to room temperature. The reaction mixture was filtered through celite and washed with ethyl acetate. The filtrate was washed with water and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by prep TLC to give 72 mg 4-[1-(3-fluoro-benzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydro-quinazolin-5-yl]-piperazine-1-carboxylic acid tert-butyl ester as yellow solid (75 mg, 35%).

1. temperaturethe solution was heated at 95° C.–100° C. for 1 hour
2. filtrationThe reaction mixture was filtered through celite
3. washwashed with ethyl acetate
4. washThe filtrate was washed with water and brine
5. dry with materialAfter drying over MgSO4
6. concentrationthe organic fraction was concentrated in vacuo
7. customresulting brown residue
8. customwas purified by prep TLC