反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 100 °C
PROCEDURE
实验过程
A mixture of compound tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate (834 mg, 0.49 mmol), tributyl(1-ethoxyvinyl)tin (356 mg, 0.98 mmol), tetrakis(triphenylphosphine)palladium (56.9 mg, 0.049 mmol) in dioxane (6 mL) was degassed with argon for five minutes. It was then heated at 100° C. in a sealed tube for 16 h, at which time LC/MS analysis confirmed full consumption of starting material. On cooling, the solvent was rotoevaporated, and the crude residue was redissolved in EtOAc, washed with 0.5 M KF solution, brine (1×25 mL), and dried over MgSO4. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel. Elution with EtOAc/Hexanes gave tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate. The enol ether was then treated with 20% TFA/CH2Cl2 (10 mL) for 2 h at room temperature. Concentration afforded 5-(8-azabicyclo[3.2.1]octan-3-yl)-3-(6-phenylpyridin-3-yl)-8,9-dihydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-6(7H)-one as an TFA salt. LCMS tR=0.67 Min (5 min run, UV254nm). Mass calculated for, M+ 450.2, observed LC/MS m/z 451.0 (M+H).
WORKUP
后处理
- customwas degassed with argon for five minutes
- customconsumption of starting material
- temperatureOn cooling
- dissolutionthe crude residue was redissolved in EtOAc
- washwashed with 0.5 M KF solution, brine (1×25 mL)
- dry with materialdried over MgSO4
- customThe solvent was removed in vacuo
- customthe residue was purified by column chromatography on silica gel
- washElution with EtOAc/Hexanes