Potassium Phosphate, Tribasic → 1-Cyclopropyl-3-(2-fluoro-4-methylsulfanyl-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

In a high-pressure tube was placed 3-amino-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester (307.6 mg, 1.33 mmol), 2-fluoro-4-methylsulfanyl-phenylamine (500.0 mg, 2.26 mmol, 1.7 eq), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (115.5 mg, 0.20 mmol, 1.5 eq), tris(dibenzylideneacetone)di-palladium(0) (91.4 mg, 0.10 mmol, 0.75 eq), and potassium phosphate (564.7 mg, 2.6 mmol, 2.0 eq) in degassed anhydrous toluene (21 mL). The tube was sealed tightly and the reaction mixture was heated to 100° C. for 17 h and cooled to room temperature. The reaction mixture was diluted with ethyl acetate (100 ml) and then filtered through a pad of Celite®. The celite pad was rinsed with EtOAc (2×50 mL), and the filtrate was concentrated under reduced pressure. The crude residue was then purified by flash column chromatography (silica, ISCO, 45 mL/min, 25 to 100% EtOAc in hexane) to afford the title compound as an orange glassy solid (339.6 mg, 68.7%). 1H-NMR (500 MHz, MeOD) δ ppm 8.36 (s, 1H), 8.24 (d, J=6.13 Hz, 1H), 7.59 (d, J=6.14 Hz, 1H), 7.14 (d, J=11.72 Hz, 1H), 7.08-6.93 (m, 2H), 3.95 (s, 3H), 3.59-3.47 (m, 1H), 2.47 (s, 3H), 1.25-1.21 (m, 2H), 0.92-0.89 (m, 2H); LC-MS (method C): [M+H]+=371.8, RT=0.80 min.

Provenance & Evidence