4-Fluorobenzylamine → 2-Bromo-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

To a mixture of 2-bromo-4-methylthiazole-5-carboxylic acid (2.00 g, 9.00 mmol) in anhydrous tetrahydrofuran (40 mL) was added N,N-diisopropylethylamine (4.67 mL, 27.0 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.41 g, 12.6 mmol). The reaction mixture was stirred at ambient temperature for 30 minutes, followed by the addition of 1-hydroxybenzotriazole (1.70 g, 12.60 mmol) and (4-fluorophenyl)methanamine (2.50 g, 12.60 mmol). The reaction mixture was stirred at ambient temperature for 18 hours. The solvent was concentrated to half in vacuo. The residue was diluted with ethyl acetate (200 mL), washed sequentially with 10% aqueous hydrochloric acid (50 mL), saturated bicarbonate solution (50 mL) and brine (100 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was recrystallized in ethyl acetate and hexane to afford the title compound as a colorless solid (2.38 g, 81%): 1H NMR (300 MHz, CDCl3) δ 7.30-7.26 (m, 2H), 7.05-7.00 (m, 2H), 5.99-5.87 (m, 1H), 4.54 (d, J=5.7 Hz, 2H), 2.63 (s, 3H).

1. stirringThe reaction mixture was stirred at ambient temperature for 18 hours
2. concentrationThe solvent was concentrated to half in vacuo
3. additionThe residue was diluted with ethyl acetate (200 mL)
4. washwashed sequentially with 10% aqueous hydrochloric acid (50 mL), saturated bicarbonate solution (50 mL) and brine (100 mL)
5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was recrystallized in ethyl acetate

ORD record

ord-19c9cfcb568d4b06a9019d746917246f

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501746B2