Benzylamine → 2-Bromo-4-methyl-thiazole-5-carboxylic acid benzylamide

To a mixture of 2-bromo-4-methylthiazole-5-carboxylic acid (10.00 g, 45.03 mmol) and 1-(3-dimethyl)aminopropyl)-3-ethylcarbodiimide hydrochloride (12.09 g, 63.04 mmol) in tetrahydrofuran (170 mL) under nitrogen atmosphere was added N,N-diisopropylethylamine (17.46 g, 135.0 mmol). After the mixture was stirred at ambient temperature for 30 minutes, 1-hydroxybenzotriazole (8.52 g, 63.04 mmol) and benzylamine (6.76 g, 6.88 mL, 63.04 mmol) were added. The mixture was stirred at ambient temperature for 16 hours and concentrated in vacuo. The residue was dissolved in dichloromethane (500 mL), washed with water (2×100 mL) and brine (2×100 mL). The organic layer was dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography (ethyl acetate:petroleum ether, 2:1) to afford the title compound (11.91 g, 85%): 1H NMR (300 MHz, DMSO-d6) δ 9.92 (t, J=6.0 Hz, 1H), 7.34-7.25 (m, 5H), 4.46 (d, J=6.0 Hz, 2H), 2.53 (s, 3H); MS (ES+) m/z 298.1 (M+1), 300.1 (M+1).

1. stirringThe mixture was stirred at ambient temperature for 16 hours
2. concentrationconcentrated in vacuo
3. dissolutionThe residue was dissolved in dichloromethane (500 mL)
4. washwashed with water (2×100 mL) and brine (2×100 mL)
5. dry with materialThe organic layer was dried over anhydrous sodium sulphate
6. filtrationfiltered
7. concentrationThe filtrate was concentrated in vacuo
8. customthe residue was purified by column chromatography (ethyl acetate:petroleum ether, 2:1)

ORD record

ord-fc3a6deb1bb242859df0dd93a65188c2

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258160B2