反应详情

温度

-78 °C

To a solution of N,N-diethyl-2,3-dimethyl-benzamide (578 mg, 2.82 mmol) in anhydrous THF (3 mL) under N2 at −78° C. was added dropwise n-BuLi (2.5M in n-hexanes, 2.4 mL, 5.92 mmol) to give a deep red solution. The reaction mixture was stirred at −78° C. for 30 minutes. The reaction mixture was transferred dropwise, via syringe, to a reaction vessel containing 4-cyano-N-methyl-N-(1-methyl-piperidin-4-yl)-benzamide (725 mg, 2.82 mmol) in anhydrous THF (5 mL) at −78° C. and under N2. The reaction mixture was stirred at −78° C. for 3.5 h. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (10 mL) and CH2Cl2 (10 mL). The combined organic layers concentrated in vacuo and the resultant solid was triturated with 2:1 isohexane/EtOAc, filtered and dried in vacuo. The crude material was purified by silica gel column chromatography, eluting with CH2Cl2 and increasing the polarity to 15% MeOH/CH2Cl2 to afford N-methyl-4-(5-methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-N-(1-methyl-piperidin-4-yl)-benzamide as a white solid (487 mg, 44%).

1. customto give a deep red solution
2. customThe reaction mixture was transferred dropwise, via syringe, to a reaction vessel
3. stirringThe reaction mixture was stirred at −78° C. for 3.5 h
4. extractionthe reaction mixture was extracted with EtOAc (10 mL) and CH2Cl2 (10 mL)
5. concentrationThe combined organic layers concentrated in vacuo
6. customthe resultant solid was triturated with 2:1 isohexane/EtOAc
7. filtrationfiltered
8. customdried in vacuo
9. customThe crude material was purified by silica gel column chromatography
10. washeluting with CH2Cl2
11. temperatureincreasing the polarity to 15% MeOH/CH2Cl2