O-Phenylenediamine → N-(2-aminophenyl)-3-fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide

Participants

Reaction Steps

100 mg of 3-fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinic acid (0.266 mmol, 1 eq.; Intermediate 1A) were suspended in 2 mL of DMF and then 28,754 mg 1,2-diaminobenzene (0.266 mmol, 1 eq.), 215,339 mg of HATU (0.566 mmol, 2.13 eq.) and 73,196 mg of N,N-Diisopropylethylamine (0.566 mmol, 2.13 eq.) were added and stirring was continued at 50° C. temperature for 18 h. The reaction mixture was partitioned between 20 ml of ethyl acetate and 20 ml of brine. The aqueouse layer was reextracted twice with 20 ml of ethyl acetate each. The combined organic layers were dried over a silicone filter and concentrated in vacuo. The residue was purified by flash chromatography to afford 69 mg of the target compound in 72% UV-purity. This material was used for the next step without further purification.

Provenance & Evidence