2-(4-Fluoroanilino)isonicotinic acid synthesis

Yield:868734-50-3 50%

Reaction Conditions:

Stage #1: 2-fluoropyridine-4-carboxylic acid;4-fluoroanilinewith sodium hydride in DMF (N,N-dimethyl-formamide) at 20 - 85; for 1.25 h;
Stage #2: with acetic acid in DMF (N,N-dimethyl-formamide);

Steps:

49.A

To a mixture of 2-fluoro-isonicotinic acid (Aldrich, 423 mg, 3.0 mmol) and 4-fluoroaniline (555 mg, 5.0 mmol) in DMF (18 mL) at rt was added NaH (500 mg of 60% in oil), and the mixture was heated at 85° C. for 75 min. Acetic acid (0.7 mL) was added to the reaction mixture and it was concentrated in vacuo. To the residue were added EtOAc (100 mL) and water (20 mL), stirred for 20 min and the solid was filtered, washed with EtOAc and dried to obtain the desired product (600 mg, 50%) as a tan solid. ¹H NMR (DMSO-d₆) δ 8.98 (s, 1H), 8.43 (s, 1H), 8.04 (d, 1H, J=4.9 Hz), 7.69 (dd, 2H, J=8.8, 4.9 Hz), 7.24 (s, 1H), 7.05 (dd, 2H, J=8.2, 6.0 Hz); MS (ESI⁺) m/z 233.3 (M+H)⁺.

References:

US2005/245530,2005,A1 Location in patent:Page/Page column 61