Potassium Phosphate, Tribasic → Tert-butyl 4-[4-[5-(1,3-benzoxazol-2-yl)-6-(bis(tert-butoxycarbonyl)amino)-3-pyridyl]-3-(methoxymethyl)pyrazol-1-yl]piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

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 (808 mg), tert-butyl 4-(4-bromo-3-(methoxymethyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (439 mg), trisdibenzylideneacetone dipalladium (53.7 mg), dicyclohexyl-[2-(2,6-dimethoxyphenyl)phenyl]phosphane (48.2 mgl) and potassium phosphate (0.233 g) in a mixture of dioxane (14 ml) and water (350 μl) was degassed. The resulting suspension was stirred at 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 30 to 80% 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-(methoxymethyl)pyrazol-1-yl]piperidine-1-carboxylate (616 mg). The N-tert-butoxycarbonyl groups on the resultant product were removed by conventional treatment with hydrogen chloride in isopropanol to afford 3-(1,3-benzoxazol-2-yl)-5-[3-(methoxymethyl)-1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine (300 mg).

Provenance & Evidence