1-Hydroxybenzotriazole → 2-(1-(cyclopropylmethyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-(pyridin-4-ylmethyl)thiazole-5-carboxamide

To a solution of 2-(1-(cyclopropylmethyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxylic acid (0.15 g, 0.53 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.14 g, 0.69 mmol) and N,N-diisopropylethylamine (0.09 mL, 0.69 mmol) in N,N-dimethylformamide (10 mL) was added 1-hydroxybenzotriazole (0.09 g, 0.69 mmol). The resulting mixture was stirred at ambient temperature for 15 minutes, followed by the addition of 4-aminomethylpyridine (0.07 mL, 0.69 mmol). The reaction mixture was kept stirring at ambient temperature for 20 hours, diluted with ethyl acetate (200 mL) and washed with water and brine. The organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography to afford the title compound in 49% yield (0.10 g): mp 169-170° C.; 1H NMR (300 MHz, CDCl3) δ 8.64-8.48 (m, 2H), 8.28-8.25 (m, 1H), 7.26-7.20 (m, 2H), 6.22 (t, J=5.8 Hz, 1H), 4.60 (d, J=5.8 Hz, 2H), 3.71 (d, J=7.2 Hz, 2H), 2.67 (s, 3H), 1.30-1.17 (m, 1H), 0.62-0.54 (m, 2H), 0.43-0.135 (m, 2H); MS (ES+) m/z 371.2 (M+1).

1. stirringThe reaction mixture was kept stirring at ambient temperature for 20 hours
2. washwashed with water and brine
3. dry with materialThe organic solution was dried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationThe filtrate was concentrated in vacuo
6. customthe residue was purified by column chromatography

ORD record

ord-4487b586fb9246d386562e420e5f7407

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318949B2