Cesium carbonate → 3-[(2-Fluoro-4-iodophenyl)amino]-5-[(4-methylpent-3-en-1-yl)oxy]isonicotinamide

Participants

Reaction Conditions

Reaction Steps

500 mg of 3-fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide (0.253 mmol, 1. eq.) were dissolved in 5 ml of DMF, then 1225 mg of cesium carbonate (3.759 mmol, 3 eq.) and 125 mg of 4-methyl-3-pentene-1-ol (0.253 mmol, 1 eq.) were added. The resulting mixture was stirred at 70° C. bath temperature for 24 hours. Since the reaction was not complete, the mixture was stirred for another 2 days at 70° C. bath temperature. Since the reaction was not complete, another 125 mg of 4-methyl-3-pentene-1-ol (0.253 mmol, 1 eq.) and 408 mg of cesium carbonate (0.253 mmol, 1 eq.) were added, and the mixture was stirred for another 2 days at 70° C. bath temperature. The resulting mixture was partitioned between aq. NH4Cl solution (50 ml) and dichloromethane (50 ml). The phases were separated and the aqueouse layer was reextracted twice with dichloromethane (50 ml each). The combined organic layers were washed with brine (50 ml), dried over a silicone filter and concentrated in vacuo. The residue was suspended in ethyl acetate and stirred for 1 h, after which the precipitate was filtered off and dried in vacuo to yield 252 mg (0.52 mmol, 42%) of the analytically pure target compound.

Provenance & Evidence