反应详情

温度

50 °C

0.5 M solution of zinc chloride in tetrahydrofuran (4.52 mL) is added dropwise at room temperature to a mixture of N-hydroxy-isobutyramidine (58 mg) and N-(1-cyano-piperidin-4-yl)-N-cyclopropyl-6-(4-methanesulfonyl-phenyl)-nicotinamide (160 mg) in ethyl acetate (8 mL). The reaction mixture is stirred at 50° C. for two days and cooled to room temperature. The precipitate is filtered off and heated to 100° C. for 1 h in a mixture of ethanol (6 mL) and glacial acetic acid (3 mL). The solvents are evaporated in vacuo and dichloromethane and 10% aqueous K2CO3 solution are added to the residue. The organic phase is separated, washed with brine, dried over MgSO4 and concentrated in vacuo. The residue is triturated with diethyl ether to give the title compound. LC (method 8): tR=1.51 min; Mass spectrum (ESI+): m/z=510 [M+H]+.

1. temperaturecooled to room temperature
2. filtrationThe precipitate is filtered off
3. temperatureheated to 100° C. for 1 h in a mixture of ethanol (6 mL) and glacial acetic acid (3 mL)
4. customThe solvents are evaporated in vacuo and dichloromethane and 10% aqueous K2CO3 solution
5. additionare added to the residue
6. customThe organic phase is separated
7. washwashed with brine
8. dry with materialdried over MgSO4
9. concentrationconcentrated in vacuo
10. customThe residue is triturated with diethyl ether