Benzylamine → N-Benzyl-2-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-4-methylthiazole-5-carboxamide

To a solution of 4-methyl-2-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)thiazole-5-carboxylic acid (0.10 g, 0.29 mmol) and 4-methylmorpholine (0.032 mL, 0.29 mmol) in anhydrous dichloromethane (6 mL) was added isobutylchloroformate (0.044 mL, 0.34 mmol) dropwise at 0° C. After stirring at ambient temperature for 2 hours, the reaction mixture was cooled to 0° C. and benzylamine (0.032 mL, 0.29 mmol) was added dropwise. Stirring at ambient temperature was continued for 18 hours, then the reaction mixture was diluted with ethyl acetate (30 mL) and washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was triturated with a mixture of ethyl acetate/dichloromethane 1/1 (10 mL) to afford the title compound as a white solid (0.055 g, 44%): mp 219-220° C. (ethyl acetate/dichloromethane); 1H NMR (300 MHz, CDCl3) δ 8.67 (d, J=8.1 Hz, 1H), 7.47-7.15 (m, 10H), 6.22 (dd, J=8.1, 2.6 Hz, 1H), 6.14 (t, J=5.6 Hz, 1H), 6.05 (d, J=2.6 Hz, 1H), 5.03 (s, 2H), 4.58 (d, J=5.6 Hz, 2H), 2.68 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.4, 162.3, 162.0, 153.5, 152.2, 137.8, 134.6, 131.6, 128.9, 128.8, 127.9, 127.8, 127.7, 122.4, 104.1, 97.4, 70.8, 44.1, 17.3; (ES+) m/z 432.2 (M+1).

1. temperaturethe reaction mixture was cooled to 0° C.
2. stirringStirring at ambient temperature
3. waitwas continued for 18 hours
4. washwashed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL)
5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was triturated with a mixture of ethyl acetate/dichloromethane 1/1 (10 mL)

ORD record

ord-1d722371ec574bf2a6dfd29d3585023c

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501746B2