Potassium Phosphate, Tribasic → 2-(2-Fluoro-4-methylsulfanyl-phenylamino)-6-formylaminomethyl-nicotinic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-chloro-6-formylaminomethyl-nicotinic acid methyl ester (123 mg, 0.54 mmol) in toluene (1.6 mL) was added potassium phosphate (119 mg, 0.76 mmol), 2-fluoro-4-methylsulfanyl-phenylamine (102 mg, 0.65 mmol), tris(dibenzylideneacetone)dipalladium (12.8 mg, 0.014 mmol) and dicyclohexyl-(2′,6′-diisopropoxy-biphenyl-2-yl)-phosphane (25 mg, 0.054 mmol). The reaction mixture was degassed with argon then heated at 100° C. After 25 hours, the reaction mixture was cooled, diluted with ethyl acetate and washed with a saturated aqueous solution of ammonium chloride, water then brine. The organic phase was isolated, dried (Na2SO4), filtered and concentrated in vacuo. The residue was triturated with ethyl acetate to afford the title compound as a bright yellow solid (43 mg, 23%). LCMS (method B): RT=3.53 min, [M+H]+=350.

Provenance & Evidence