1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-amino-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

To a solution of 2-amino-4-methylthiazole-5-carboxylic acid (4.20 g, 26.0 mmol) in anhydrous N,N-dimethylformamide (100 mL) was added 1-hydroxybenzotriazole (9.30 g, 69.0 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (6.60 g, 34.0 mmol), diisopropylethylamine (4.40 g, 34.0 mmol), and (4-fluorophenyl)methanamine (3.97 g, 32.0 mmol). The reaction mixture was stirred at ambient temperature for 18 hours and N,N-dimethylformamide was removed in vacuo. The residue was dissolved in ethyl acetate (400 mL) and washed with saturated aqueous sodium bicarbonate (2×100 mL) and brine (100 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo to afford the title compound as a yellowish solid in 80% yield (5.60 g): 1H NMR (300 MHz, CDCl3) δ 7.39-7.17 (m, 2H), 7.01 (t, J=8.3 Hz, 2H), 5.78 (br s, 1H), 5.34 (br s, 2H), 4.50 (d, J=5.6 Hz, 2H), 2.47 (s, 3H); MS (ES+) m/z 266.2 (M+1).

1. customN,N-dimethylformamide was removed in vacuo
2. dissolutionThe residue was dissolved in ethyl acetate (400 mL)
3. washwashed with saturated aqueous sodium bicarbonate (2×100 mL) and brine (100 mL)
4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationthe filtrate was concentrated in vacuo

ORD record

ord-fbf0d3e967df485296a2ce4573524b53

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08236835B2