反应详情

温度

120 °C

Compound [1] was prepared using the following procedure: A mixture of tert-butyl N-[3-(1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate (291 mg), tert-butyl 4-(4-bromo-3-cyanopyrazol-1-yl)piperidine-1-carboxylate (150 mg), tris(dibenzylideneacetone)dipalladium (19.33 mg), dicyclohexyl-[2-(2,6-dimethoxyphenyl)phenyl]phosphine (17.34 mg) and potassium phosphate (0.084 g) in a mixture of dioxane (5 ml) and water (150 μl) was degassed. The resulting suspension was stirred and heated to 120° C. for 3 hours under argon. After the mixture was cooled to room temperature the solvent was concentrated, ethyl acetate (80 ml) and water (20 ml) were added. The organic layer was washed with brine, dried over Magnesium sulphate, filtered and evaporated under reduce pressure. The crude product was purified by flash chromatography on silica gel eluting with 20 to 75% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford tert-butyl 4-[4-[5-(1,3-benzoxazol-2-yl)-6-(bis(tert-butoxycarbonyl)amino)-3-pyridyl]-3-cyano-pyrazol-1-yl]piperidine-1-carboxylate (251 mg) as pale pink foam. The N-tert-butoxycarbonyl groups on the resultant product were removed using the procedure described for example 61. The product gave the following characterizing data: NMR Spectrum: (DMSOd6) 1.82 (dd, 1H), 1.87 (dd, 1H), 2.01-2.09 (m, 2H), 2.58-2.67 (m, 2H), 3.04-3.12 (m, 2H), 4.34-4.42 (m, 1H), 7.43-7.52 (m, 2H), 7.81 (dd, 1H), 7.87 (dd, 1H), 7.92 (bs, 2H), 8.58 (s, 2H), 8.51 (s, 1H); Mass spectrum: M+H+ 386.

1. customwas degassed
2. temperatureAfter the mixture was cooled to room temperature the solvent
3. concentrationwas concentrated
4. additionethyl acetate (80 ml) and water (20 ml) were added
5. washThe organic layer was washed with brine
6. dry with materialdried over Magnesium sulphate
7. filtrationfiltered
8. customevaporated
9. customThe crude product was purified by flash chromatography on silica gel eluting with 20 to 75% ethyl acetate in petroleum ether
10. customThe solvent was evaporated to dryness