4-Methylmorpholine → 2-Bromo-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

To a solution of 2-bromo-4-methylthiazole-5-carboxylic acid (2.25 g, 10.00 mmol) and 4-methylmorpholine (1.25 g, 11.00 mmol) in anhydrous dichloromethane (80 mL) was added iso-butyl chloroformate (1.3 mL, 10.0 mmol) dropwise at 0° C. The reaction mixture was stirred at ambient temperature for 2 hours, cooled to 0° C. and pyridin-3-ylmethanamine (1.23 g, 12.00 mmol) was added dropwise. The reaction mixture was stirred at ambient temperature for 4 hours, diluted with ethyl acetate (100 mL) and washed with saturated aqueous sodium bicarbonate (50 mL) and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate) to afford the title compound as a yellow solid (1.78 g, 56%): 1H NMR (300 MHz, CDCl3) δ 8.55-8.48 (m, 2H), 7.70-7.64 (m, 1H), 7.29-7.26 (m, 1H), 6.36 (t, J=5.8 Hz, 1H), 4.56 (d, J=5.8 Hz, 2H), 2.63 (s, 3H); MS (ES+) m/z 312.1 (M+1), 314.1 (M+1).

1. temperaturecooled to 0° C.
2. stirringThe reaction mixture was stirred at ambient temperature for 4 hours
3. washwashed with saturated aqueous sodium bicarbonate (50 mL) and brine (50 mL)
4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography (ethyl acetate)

ORD record

ord-713fc77c04ce44c2ac18fe2cc25413e9

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258160B2