反应详情

温度

100 °C

A mixture of 4-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-4-yl]-2-chlorofuro[2,3-c]pyridin-7-amine (83 mg, 0.18 mmol), 3,5-bis(trifluoromethyl)benzeneboronic acid (71 mg, 0.28 mmol), (1,1′-bis-(diphenylphosphino)ferrocene)palladium dichloride (13.5 mg, 0.0186 mmol), and potassium carbonate (77 mg, 0.56 mmol) in 1,4-dioxane (1.0 mL) and water (0.30 mL) was degassed 3× with argon and heated in a microwave reactor at 100° C. for 1 h. The mixture was partitioned between EtOAc and brine and the aqueous phase was extracted with EtOAc. The combined organic fractions were dried over sodium sulfate and concentrated. Purification of the residue by ISCO chromatography (0 to 5% 7 N NH3/MeOH:DCM) afforded 104 mg (90%) of the title compound as a foam. 1H NMR (400 MHz, CDCl3): δ 0.06-0.14 (m, 6H) 0.87-0.98 (m, 9H) 1.49-1.64 (m, 2H) 1.85-2.11 (m, 4H) 2.18-2.33 (m, 2H) 3.69-3.82 (m, 2H), 4.17-4.28 (m, 1H), 5.05 (br. s., 1H) 7.34 (s, 1H) 7.70 (s, 1H) 7.82 (s, 1H) 7.92 (s, 1H) 8.00 (s, 1H) 8.31 (s, 2H); MS (ESI): 624.34 [M+H]+; HPLC tR=2.00 min (TOF: nonpolar—3 min).

1. customwas degassed 3× with argon
2. customThe mixture was partitioned between EtOAc and brine
3. extractionthe aqueous phase was extracted with EtOAc
4. dry with materialThe combined organic fractions were dried over sodium sulfate
5. concentrationconcentrated
6. customPurification of the residue by ISCO chromatography (0 to 5% 7 N NH3/MeOH:DCM)