反应详情

A suspension of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (858 mg, 2.8 mmol), 4-ditert-butylphosphanyl-N,N-dimethyl-aniline; dichloropalladium (164 mg, 0.23 mmol), methyl 3-[bis(tert-butoxycarbonyl)amino]-6-bromo-pyrazine-2-carboxylate (1.0 g, 2.3 mmol), and Na2CO3 (490 mg, 4.6 mmol) under an atmosphere of nitrogen in toluene (15 mL) and water (2 mL) was heated to 95° C. for 2 h. The reaction mixture was diluted with ethyl acetate, washed with 1N HCl, 50% saturated sodium bicarbonate solution, and brine. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified via silica gel column chromatography using 10-50% ethyl acetate/hexane to provide methyl 3-[bis(tert-butoxycarbonyl)amino]-6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazine-2-carboxylate (1.2 g, 97%) as a amber oil. 1H NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 6.97 (s, 1H), 4.12 (s, 2H), 3.89 (s, 3H), 3.57 (t, J=5.2 Hz, 2H), 2.61 (s, 2H), 1.43 (s, 9H), 1.34 (s, 18H). LC/MS m/z 535.5 [M+H]+.

1. washwashed with 1N HCl, 50% saturated sodium bicarbonate solution, and brine
2. dry with materialThe organic layer was dried over anhydrous Na2SO4
3. filtrationfiltered
4. concentrationconcentrated
5. customThe crude product was purified via silica gel column chromatography