Oxalyl chloride → HCID 178521817, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 1-phenylcyclopropane-1-carboxylic acid (2.0 g, 12.3 mmol) in dichloromethane (40 mL) was treated at ambient temperature with oxalyl chloride (1.06 mL, 12.3 mmol) and three drops of DMF. A drying tube was placed on the flask and the reaction bubbled (HCl, CO, and CO2) for three hours. 2-Thiazol-4-yl-3H-benzoimidazol-5-ylamine (1-6, 2.67 g, 12.3 mmol) and diisopropyl ethyl amine (3.22 mL, 18.5 mmol) were dissolved in 30 mL of dry N,N-dimethylformamide and cooled to 0° C. The acid chloride solution was concentrated, re-dissolved in 10 mL of dichloromethane, and cannulated into the stirring amine solution over a five minute period. The reaction was allowed to warm slowly to ambient temperature after the addition was complete. The reaction was complete after half an hour by TLC analysis and was partitioned between ethyl acetate and dilute sodium bicarbonate solution. The aqueous was extracted (3×10 mL) with ethyl acetate and the layers were separated. The organic layer was washed twice with water, once with brine, separated, dried (MgSO4), filtered, and concentrated in vacuo. The resulting yellow oil was filtered thru a plug of silica gel eluted with ethyl acetate. The filtrate was concentrated in vacuo and the residue was triturated in ethyl acetate/hexanes mixtures to afford the pure 1-phenyl-N-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-5-yl]cyclopropanecarboxamide as a white solid (3-10); 1H NMR (500 MHz, DMSO-d6) δ 12.87 (s, 1H), 9.31 (s, 1H), 9.10 (s, 1H), 8.42 (s, 1H), 7.95 (s, 1H), 7.49 (d, 1H), 7.36 (m, 6H), 1.48 (dd, 2H, J=4.4, 2.4 Hz), 1.15 (dd, 2H, J=4.4, 2.4 Hz).

Provenance & Evidence