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

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).

1. additionwas added to the reaction mixture
2. extractionthe aqueous solution was extracted with EtOAc (20 mL×2)
3. washThe combined organic layers were washed with water (100 mL×2)
4. customThe organic layer was dried
5. concentrationconcentrated
6. customproviding a residue which
7. customwas purified by silica gel (60-120 mesh) column chromatography
8. washeluting with 40-50% EtOAc in petroleum ether

ORD-Eintrag

ord-cd144443e12a496d861d9012a34e634c

Quelldatensatz

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08710043B2