75% |
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 116℃; for 1.5h;Inert atmosphere; Microwave irradiation; |
To a suspension of <strong>[59786-31-1]methyl 3-bromoisonicotinate</strong> (220 mg, 1.02 mmol), 3-amino-6-fluoro-1-methyl-indazole (220 mg, 1.33 mmol), Cs2CO3 (500 mg, 1.53 mmol), and Xantphos (89 mg, 0.15 mmol) in dioxane (5 mL) was added Pd2(dba)3 (47 mg, 0.051 mmol) under N2 at rt. The suspension was heated at 116° C. in a microwave for 90 min. The reaction was filtered and concentrated. Purification by silica gel chromatography (10percent-40percent EtOAc/DCM) gave 228 mg (75percent) of the intermediate ester as a yellow solid. The ester was hydrolyzed in 1N NaOH (1 mL) in MeOH (5 mL) at 35° C. for 1 h. The solution was neutralized with HOAc and concentrated. The residue was taken up in water, sonicated, and the solid was collected by filtration. The solid was taken up in MeOH and collected by filtration to give 148 mg (71percent) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): delta 3.96 (3H, s), 7.02 (1H, td, J=8.9, 1.6 Hz), 7.50 (1H, d, J=8.2 Hz), 7.63 (1H, dd, J=8.7, 5.0 Hz), 7.79 (1H, d, J=5.0 Hz), 8.18 (1H, d, J=5.0 Hz), 9.67 (1H, s), 10.59 (1H, br s), 14.20 (1H, br s). [M+H] calc'd for C14H11FN4O2, 287. found 287. |