Hydrochloric Acid → (S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-methoxy-6-nitropicolinamide

Participants

Reaction Steps

To a stirred solution of 5-methoxy-6-nitropicolinic acid (200 mg, 0.001 mol) in DMF was added EDCI. HCl (231.6 mg, 0.0012 mol, Molekula, India) followed by HOBt (164.7 mg, 0.0012 mol, Spectrochem, India), DIPEA (521.87 mg, 0.0040 mol, Spectrochem, India) and (S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride (349.83 mg, 0.0010 mmol, Intermediate 6) at 0° C. The reaction mixture was stirred at room temperature overnight. After completion of the reaction (monitored by TLC, 50% EtOAc in hexane), water (20 mL) was added to the reaction mixture, and the aqueous solution was extracted with EtOAc (20 mL×2). The combined organic layers were washed with water (100 mL×2). The organic layer was dried and concentrated providing a residue which was purified by silica gel (60-120 mesh) column chromatography eluting with 40-50% EtOAc in petroleum ether to give the title compound as a solid. 1H-NMR (400 MHz, DMSO-d6): δ 9.46 (d, J=7.6 Hz, 1H), 8.53 (d, J=4.4 Hz, 1H), 8.34 (d, J=8.4 Hz, 1H), 8.12 (d, J=8.8 Hz, 1H), 7.83 (t, J=9.6 Hz, 1H), 7.58-7.55 (m, 3H), 7.35 (d, J=8.4 Hz, 1H), 6.57 (d, J=7.2 Hz, 1H), 4.04 (s, 3H). MS (ESI, positive ion) m/z: 485 (M+H).

Provenance & Evidence