反应详情

A mixture of 5-Bromo-3-[1-(6-chloro-3-fluoro-2-hydroxyphenyl)ethyl]pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (100.00 mg, 0.21289 mmol), 1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (134 mg, 0.319 mmol), Pd(PPh3)4 (12.3 mg, 0.0106 mmol), potassium carbonate (147.1 mg, 1.064 mmol) and 4:1 Dioxane:water (4:1,1,4-Dioxane:H2O, 8 mL, 80 mmol) was heated in a microwave reactor at 100° C. for 30 min. Reaction mixture was cooled to rt, 12 M HCl in H2O (0.8 mL, 10 mmol) was added, and the solution was heated at 40° C. for 2 h. Purification by Teledyne/ISCO eluting with 0-15% MeOH in DCM afforded the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.37-1.59 (m, 2H), 1.84 (d, J=7.3 Hz, 3H), 1.89-2.14 (m, 6H), 2.16-2.27 (m, 3H), 3.68 (ddd, J=10.9, 6.8, 4.3 Hz, 1H), 4.08-4.26 (m, 1H), 5.09 (br. s., 1H), 6.76-6.88 (m, 1H), 6.90-7.00 (m, 1H), 7.37 (d, J=1.3 Hz, 1H), 7.44-7.56 (m, 2H), 8.09 (d, J=2.0 Hz, 1H).

1. customReaction mixture
2. temperaturethe solution was heated at 40° C. for 2 h
3. customPurification by Teledyne/ISCO
4. washeluting with 0-15% MeOH in DCM