Isoniazid → N-cyclopentyl-2-naphthalen-1-yl-N-[2-(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)ethyl]acetamide

Participants

Reaction Steps

A DMF (5 mL) solution of N-(2-cyanoethyl)cyclopentylamine (4.7 mL, 32. mmol) was added to a stirred solution of HATU (15.3 g, 40.3 mmol), 1-naphthylacetic acid (5.0 g, 27 mmol), and diisopropylethylamine (7.0 mL, 40 mmol) in DMF (40 mL). The mixture stirred at room temperature overnight. Aqueous LiCl (5%) was added and the mixture was extracted three times with ethyl acetate (100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was carried to next step without further purification. A sample of this product (3.35 g, 11.0 mmol), isonicotinic hydrazide (1.0 g, 7.3 mmol) and sodium methoxide (600 mg, 11 mmol) was transferred to a pressure tube. Ethanol (4 mL) was added and the reaction was stirred at 120° C. overnight. The reaction was monitored by LCMS. Upon completion, the ethanol was removed in vacuo to afford the product as a solid. The crude mixture was separated by preparative HPLC and lyophilized to afford a solid. 1H NMR (400 MHz, d6-DMSO): δ 8.8 (m, 2H), 8.2 (m, 2H), 8.0-7.85 (m, 2H), 7.8-7.7 (m, 1H), 7.6-7.3 (m, 4H), 4.5-4.3 (m, 2H), 3.5 (t, 2H), 3.3-3.0 (m, 2H), 1.8-1.3 (m, 9H). MS (EI) for C26H27N5O: 426 (MH+).

Provenance & Evidence