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
- 65 °C
PROCEDURE
实验过程
tert-butyl (5-bromo-3-(3-phenylisoxazol-5-yl)pyrazin-2-yl)-N-tert-butoxycarbonyl-carbamate (750 mg, 1.393 mmol) and tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate (691.5 mg, 1.532 mmol) were suspended in MeCN (7.500 mL)/water (7.500 mL) and Na2CO3 (1.393 mL of 2 M, 2.786 mmol) was added. The reaction mixture was degassed with 3× nitrogen/vacuum cycles. Pd(tBu3P)2 (71.19 mg, 0.1393 mmol) was added and the reaction mixture again degassed 3 times then heated to 65° C. (Dry Syn Temp) for 1.5 hours. The reaction mixture was cooled to ambient temperature and diluted with ethylacetate/water. The aqueous layer was extracted with ethylacetate (×1) and the combined organic extracts washed with brine (×2), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 80 g column, eluting with 0 to 30% Petroleum/Petroleum Ether, loaded in DCM) to give tert-butyl 3-((4-(5-((tert-butoxycarbonyl)amino)-6-(3-phenylisoxazol-5-yl)pyrazin-2-yl)phenyl)sulfonyl)piperidine-1-carboxylate as a yellow solid (1.01 g, 93% Yield). H NMR (400.0 MHz, DMSO) δ 9.53 (s, 1H), 8.67 (d, 2H), 8.12 (d, 2H), 8.05-8.03 (m, 3H), 7.60-7.57 (m, 3H), 3.76 (br d, 1H), 3.47-3.41 (m, 1H), 3.02-2.95 (m, 1H), 2.81-2.77 (m, 1H), 2.09-2.04 (m, 1H), 1.77-1.63 (m, 2H) and 1.42-1.21 (m, 29H) ppm
WORKUP
后处理
- additionwas added
- customThe reaction mixture was degassed with 3× nitrogen/vacuum cycles
- customthe reaction mixture again degassed 3 times
- custom(Dry Syn Temp) for 1.5 hours
- temperatureThe reaction mixture was cooled to ambient temperature
- additiondiluted with ethylacetate/water
- extractionThe aqueous layer was extracted with ethylacetate (×1)
- washthe combined organic extracts washed with brine (×2)
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was purified by column chromatography (ISCO Companion, 80 g column, eluting with 0 to 30% Petroleum/Petroleum Ether, loaded in DCM)