反应详情

In a round bottom flask under nitrogen at room temperature, a mixture of 5-(3-azetidinylmethyl)-4-[2-fluoro-4-(7-quinolinyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (0.38 mmol) in dichloromethane (2 mL) was treated with N,N-diisopropylethylamine (0.77 mmol) by syringe and stirred for 2 min. The starting material did not dissolve. N-methyl-2-pyrrolidone (2 mL) was added to the mixture and some material dissolved. The mixture was heated with a heat gun to accelerate dissolution and was then left to cool to room temperature. Dimethylcarbamoyl chloride (0.38 mmol) was then added dropwise by syringe to the reaction, which was stirred for 1 h. The reaction mixture was concentrated to remove the dichloromethane. The resultant solution was directly purified by reverse phase HPLC (10-70% acetonitrile/water with 0.1% NH4OH) and subsequently purified by silica gel chromatography (0-3% methanol/ethyl acetate) to provide the title compound as a white solid (31 mg, 18%). MS(ES)+ m/e 447.2 [M+H]+.

1. dissolutionThe starting material did not dissolve
2. dissolutionsome material dissolved
3. temperatureThe mixture was heated with a heat gun
4. dissolutiondissolution
5. waitwas then left
6. stirringwas stirred for 1 h
7. concentrationThe reaction mixture was concentrated
8. customto remove the dichloromethane
9. customThe resultant solution was directly purified by reverse phase HPLC (10-70% acetonitrile/water with 0.1% NH4OH)
10. customsubsequently purified by silica gel chromatography (0-3% methanol/ethyl acetate)