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

To a solution of of 2-bromo-4-methylthiazole-5-carboxylic acid (2.00 g, 9.00 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.41 g, 12.6 mmol) and N,N-diisopropylethylamine (4.67 mL, 27.0 mmol) in tetrahydrofuran (40 mL) was added 1-hydroxybenzotriazole (1.70 g, 12.6 mmol). The resulting mixture was stirred at ambient temperature for 30 minutes and 4-fluorobenzylamine (1.43 mL, 12.6 mmol) was added. The reaction mixture was kept stirring at ambient temperature for 17 hours, then concentrated in vacuo. The residue was dissolved ethyl acetate and washed with water and brine. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography to afford 2-bromo-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide in 81% yield (2.38 g): 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 kept stirring at ambient temperature for 17 hours
2. concentrationconcentrated in vacuo
3. dissolutionThe residue was dissolved ethyl acetate
4. washwashed with water and brine
5. dry with materialThe organic solution was dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by column chromatography

ORD-Eintrag

ord-6e61ecc4d4194569a3b2f4a10afdfd05

Quelldatensatz

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08063084B2