1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 1-Ethyl-2-{[2-(3-fluorophenyl)-pyrazol-3-yl]methyl}-5-cyano-1H-benzimidazole

Participants

Reaction Steps

To a stirring solution of 3-amino-4-ethylaminobenzonitrile (887 mg, 5.5 mmol) and 1-(3-Fluorophenyl)-5-carboxymethylpyrazole (1.10 g, 5 mmol) in pyridine (5 mL) is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.15 g, 6 mmol). The mixture is stirred at room temperature for 17.5 h, then concentrated. The residue is cooled in an ice bath, aqueous HCl is added with stirring, the precipitate is collected by filtration, rinsed well with water and dried. The solid is added to acetic acid (75 mL) and heated at reflux for 5.5 h. The mixture is cooled, concentrated, and purified by silica gel chromatography to give 1-Ethyl-2-{[2-(3-fluorophenyl)-pyrazol-3-yl]methyl}-5-cyano-1H-benzimidazole. The product is converted to the mesylate salt in acetone. 1H NMR (CDCl3): δ 8.17 (s, 1H), 7.89 (d, J=8.52 Hz, 1H), 7.68-7.75 (m 1H), 7.44-7.54 (m, 2H), 7.37-7.40 (m, 1H), 7.21-7.28 (m, 1H), 6.35 (d, J=1.65 Hz, 1H), 4.65 (s, 2H), 4.29 (q, J=7.14 Hz, 2H), 2.34 (s, 3H), 1.19 (t, J=7.14 Hz, 3H). LCMS 346.0 (MH+), 344.4 (MH−).

Provenance & Evidence