p-Toluenesulfonic acid → (S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-hydroxy-6-nitropicolinamide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (S)—N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-methoxy-6-nitropicolinamide (700 mg, 0.0011 mol) in NMP (7.0 mL) was added LiCl (183.79 mg, 0.0043 mol, Sigma Aldrich, India) followed by pTSA (746.63 mg, 0.0043 mol, Sigma Aldrich, India) at room temperature. The reaction mixture was stirred at 180° C. for 2 h. After completion of the reaction (monitored by TLC, 100% EtOAc), the reaction mixture was cooled to room temperature and water (50 mL) was added and the aqueous solution was extracted with EtOAc (25 mL×2). The organic extracts were washed with water (25 mL×2) and brine (25 mL) and dried over anhydrous sodium sulfate and concentrated. The resulting material was purified by silica gel (60-120 mesh) column chromatography eluting with 60-70% EtOAc in petroleum ether to give the title compound as an off-white solid. 1H-NMR (400 MHz, DMSO-d6): δ 12.77 (br. s., 1H), 9.43 (d, J=7.2 Hz, 1H), 8.57 (d, J=4.4 Hz, 1H), 8.24 (d, J=8.4 Hz, 1H), 7.86-7.79 (m, 2H), 7.59-7.54 (m, 3H), 7.37 (d, J=8.4 Hz, 1H), 6.57 (d, J=7.2 Hz, 1H). MS (ESI, positive ion) m/z: 471 (M+H).

Provenance & Evidence