Cesium carbonate → 1-Cyclopropyl-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

To a degassed suspension of 3-amino-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester (215.0 mg, 0.93 mmol), and trifluoro-methanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester (323.5 mg, 1.02 mmol, 1.1 eq) in anhydrous toluene (6.2 mL) was added Pd2dba3 (85.2 mg, 0.09 mmol, 0.1 eq), Xantphos (107.6 mg, 0.186 mmol, 0.2 eq) and Cs2CO3 (606.0 mg, 1.86 mmol, 2.0 eq). The reaction mixture was degassed with bubbling nitrogen for 10 minutes and stirred at 105° C. under N2 for 17 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (150 ml). The mixture was 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 a yellow foam (265 mg, 71.7%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.52 (s, 1H), 8.33 (d, J=6.0 Hz, 1H), 7.86 (s, 1H), 7.55 (d, J=6.0 Hz, 1H), 7.29 (d, J=11.6 Hz, 1H), 7.13 (d, J=7.9 Hz, 1H), 6.90 (s, 1H), 3.82 (s, 3H), 3.57-3.46 (m, 1H), 1.27-1.03 (m, 2H), 0.96-0.71 (m, 2H), 0.23 (s, 9H); LC-MS (method D): [M+H]+=398.2, RT=2.69 min.

Provenance & Evidence