Potassium Cyanide → HCID 11150337, compound

Participants

Reaction Conditions

Reaction Steps

4-(2-Fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide (0.20 g, 0.5 mmol) was added to potassium cyanide (0.23 g, 3.5 mmol), copper(I)iodide (excess) and tetrakis(triphenylphosphine)palladium(0) (excess) in DMF (30 ml) and heated at 110° C. for 4 h. The reaction mixture was allowed to cool to RT and filtered through Celite® to remove any solid. The Celite® pad was washed well with 5% MeOH/EtOAc. The filtrate and washings were combined and concentrated under reduced pressure. The residue was dissolved in 5% MeOH/EtOAc, then washed with water, brine, dried (Na2SO4), concentrated and triturated with EtOAc giving an approximately 1:1 mixture of 4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide and 4-(4-cyano-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide. Further purification by preparative HPLC [90% (H2O/TFA)/(acetonitrile/TFA)—1% (H2O/TFA)/(acetonitrile/TFA) gradient elution 0.8 ml/min, pH 2.5-2.6] yielded 4-(4-cyano-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide (0.01 g, 7%); m.p. 261-266° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.01 (s, 1H), 8.39 (s, 1H), 7.91 (dd and br s, J=11.2, 1.7 Hz, 2H), 7.72 (t, J=8.2 Hz, 1H), 7.66 (dd, J=8.6, 1.7 Hz, 1H), 7.52 (br s, 1H), 5.97 (s, 1H), 3.40 (s, 3H). HPLC 95.5% (254 nm). HRMS (FAB+) cald for C14H11FN4O2 286.0866 (M+), found 286.0864.

Provenance & Evidence