反应详情

Heat a mixture of tert-butyl 1-(6-chloro-4,5-dimethylpyridazin-3-yl)piperidin-4-yl(methyl)carbamate (1.5 g, 4.23 mmol), 4-cyanophenylboronic acid (932 mg, 6.34 mmol), Cs2CO3 (5.51 g, 16.9 mmol) and (SP-4-1)-bis[bis(1,1-dimethylethyl)(4-methoxyphenyl)phosphine-κP]dichloro-palladium (29 mg, 0.042 mmol) in a mixture of 1,4-dioxane (30 mL) and H2O (10 mL) under N2 at 90° C. overnight. Partition the reaction mixture between EtOAc and H2O with dissolved NaHCO3. Separate the layers, and extract the aqueous layer with EtOAc. Combine the organic layers, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2) to provide the title compound as a yellow solid (1.68 g, 94%). ES/MS m/z 422.2 (M+1).

1. temperatureHeat
2. customPartition the reaction mixture between EtOAc and H2O with dissolved NaHCO3
3. customSeparate the layers
4. extractionextract the aqueous layer with EtOAc
5. dry with materialdry over Na2SO4
6. filtrationfilter
7. concentrationconcentrate under reduced pressure
8. customPurify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2)