反应详情

Treat a solution of 4-(4,5-dimethyl-6-(4-(methylamino)piperidin-1-yl)pyridazin-3-yl)benzonitrile (90 mg, 0.28 mmol) and triethylamine (0.12 mL, 0.84 mmol) in CH2Cl2 (2.8 mL) with 4-cyanobenzoyl chloride (56 mg, 0.34 mmol). Stir the reaction at ambient temperature overnight. Wash with H2O and separate the layers. Directly purify the organic layer by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2). Concentrate to afford a white solid. Dissolve the material in MeOH and add 1.1 eq of methanolic HCl (preform by dripping acetyl chloride into MeOH). Concentrate the mixture under a stream of N2 gas and dry the residue in a vacuum oven at 45° C. to obtain the title compound as yellow solid (130 mg, 95%). ES/MS m/z 451.2 (M+1).

1. customthe reaction at ambient temperature overnight
2. washWash with H2O
3. customseparate the layers
4. customDirectly purify the organic layer by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2)
5. concentrationConcentrate
6. customto afford a white solid
7. concentrationConcentrate the mixture under a stream of N2 gas
8. customdry the residue in a vacuum oven at 45° C.