反应详情

tert-butyl N-(5-bromo-3-ethynyl-pyrazin-2-yl)-N-tert-butoxycarbonyl-carbamate (2 g, 5.022 mmol) and tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate (2.324 g, 5.148 mmol) were dissolved in MeCN (40.00 mL)/water (8.000 mL). K3PO4 (2.131 g, 10.04 mmol) was added and the mixture was degassed/flushed via nitrogen cycles (×5). Pd[P(tBu)3]2. (128.3 mg, 0.2511 mmol) was added and the reaction mixture placed under an atmosphere of nitrogen using vacuum/nitrogen cycles (×5). The reaction mixture was stirred at ambient temperature for 1 hour and then poured onto a stirred mixture of ethylacetate and saturated aqueous sodium metabisulphite at 10° C. The mixture was stirred for 5 minutes, shaken well and separated. The organic layer was washed with brine (×1), dried over MgSO4, filtered and the solution passed through a Florisil eluting with Ethylacetate. The filtrate was concentrated in vacuo and the residue purified by column chromatography (ISCO Companion, 330 g column, eluting with 0 to 40% Petroleum/Petroleum Ether, loaded in DCM) to give tert-butyl 3-[4-[5-[bis(tert-butoxycarbonyl)amino]-6-ethynyl-pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate as a beige solid (2.45 g, 76% Yield). H NMR (400.0 MHz, DMSO) δ 9.38 (s, 1H), 8.48 (d, 2H), 8.08 (d, 2H), 5.02 (s, 1H), 4.12-3.88 (m, 1H), 3.76 (br d, 1H), 3.43 (br s, 1H), 2.90-2.78 (m, 2H), 2.09 (br s, 1H), 1.75-1.61 (m, 2H) and 1.38-1.18 (m, 28H) ppm;

1. customthe mixture was degassed/flushed via nitrogen cycles (×5)
2. addition(128.3 mg, 0.2511 mmol) was added
3. additionpoured onto a stirred mixture of ethylacetate and saturated aqueous sodium metabisulphite at 10° C
4. stirringThe mixture was stirred for 5 minutes
5. stirringshaken well
6. customseparated
7. washThe organic layer was washed with brine (×1)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationThe filtrate was concentrated in vacuo
11. customthe residue purified by column chromatography (ISCO Companion, 330 g column, eluting with 0 to 40% Petroleum/Petroleum Ether, loaded in DCM)