Hydrochloric Acid → 5-(4-fluorophenyl)-1-isopropyl-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-6-oxo-1,6-dihydropyridine-3-carboxamide

To a solution of 5-(4-fluorophenyl)-6-isopropoxynicotinic acid and 5-(4-fluorophenyl)-1-isopropyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (50 mg, 0.09 mmol) in DMF (0.5 mL) were added hydrochloride salt of (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine (21.8 mg, 0.11 mmol), HATU (0.5 M in DMF; 0.27 mL, 0.14 mmol) and diisopropylethylamine (63 μL, 0.36 mmol). The mixture was stirred at ambient temperature. After 10 min, HCl (1.0 M) was added and the mixture was purified by reverse chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) to give the N-alkylated product, 5-(4-fluorophenyl)-1-isopropyl-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-6-oxo-1,6-dihydropyridine-3-carboxamide (example 5.61) (20.9 mg), HRMS 385.1685. 1H NMR (400 MHz, CDCl3): δ 8.21 (d, J=2.5 Hz, 1H); 7.69-7.63 (m, 3H); 7.12 (t, J=8.5 Hz, 2H); 6.52 (d, J=7.7 Hz, 1H); 5.60-5.51 (m, 1H); 5.37-5.27 (m, 1H); 2.41 (s, 3H); 1.70 (d, J=7.1 Hz, 3H); 1.45 (dd, J=6.8, 2.2 Hz, 6H). The o-alkylated product was repurified by reverse chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.05% ammonium hydroxide) to give 5-(4-fluorophenyl)-6-isopropoxy-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]nicotinamide (example 3.24) (16.1 mg). HRMS 385.1679. 1H NMR (400 MHz, CDCl3): δ 8.59 (s, 1H); 8.01 (d, J=2.3 Hz, 1H); 7.55 (dd, J=8.3, 5.4 Hz, 2H); 7.16-7.08 (m, 2H); 6.63 (d, J=7.7 Hz, 1H); 5.63-5.55 (m, 1H); 5.51-5.43 (m, 1H); 2.40 (s, 3H); 1.71 (d, J=7.1 Hz, 3H); 1.35 (d, J=6.2 Hz, 6H).

1. customthe mixture was purified by reverse chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

ORD record

ord-7d6be9fda9364da4929ea572296f04bc

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598209B2