反应详情

温度

80 °C

A mixture of tert-butyl 3-(4-bromo-1-methyl-1H-pyrazol-5-yl)pyrrolidine-1-carboxylate (1.0 g, 3.1 mmol), 4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-12-(tetramethyl-1,3,2-dioxaborolan-2-yl)-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1 (14),2,4,10,12-pentaene (1.1 g, 2.5 mmol), Pd(dppf)Cl2 (310 mg, 0.379 mmol), and Na2CO3 (1.34 g, 12.6 mmol) in dioxane (20 mL) was stirred at 80° C. for 16 h. The resultant mixture was extracted with ethyl acetate (50 mL), washed with brine, dried over MgSO4, filtered, and evaporated to afford the crude product, which was purified by reverse phase Combiflash eluting with a 0-70% gradient of CH3CN in 0.3% NH4HCO3 to give 1-tert-butyl-6-(1-methyl-4-{4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-5-yl)-λ3,3-oxazepan-2-one (920 mg, 46% yield) as white solid. LCMS (ESI) m/z: 559.4 [M+H+]. 1H-NMR (500 MHz, DMSO-d6) δ 8.41 (d, J=8.5 Hz, 1H), 7.91 (s, 1H), 7.48 (s, 1H), 7.09 (d, J=8.5 Hz, 1H), 6.96 (s, 1H), 5.88-5.85 (m, 1H), 4.53 (s, 4H), 3.75 (s, 3H), 3.72 (s, 1H), 3.60 (s, 1H), 3.51-3.42 (m, 2H), 3.24-3.20 (m, 1H), 2.26 (s, 3H), 2.15-2.07 (m, 2H), 1.46 (s, 6H), 1.37 (s, 9H).

1. extractionThe resultant mixture was extracted with ethyl acetate (50 mL)
2. washwashed with brine
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. customevaporated
6. customto afford the crude product, which
7. customwas purified by reverse phase Combiflash
8. washeluting with a 0-70% gradient of CH3CN in 0.3% NH4HCO3