Piperazine → 2-(4-Isopropylpiperazin-1-yl)benzothiazole-6-carbonitrile

Participants

Reaction Steps

A solution of 2-chlorobenzothiazole-6-carbonitrile (14.9 g, 0.077 mol) in DMF (250 mL) was added drop-wise at 10° C. to a mixture of anhydrous piperazine (60 g, 0.698 mol) and DMF (300 mL). Then the mixture was stirred for 2 h. Water (1,550 mL) was added and the mixture was extracted with dichloromethane (5×500 mL). The combined organic extracts was washed with water (6×500 mL), dried (Na2SO4), filtered and evaporated to give a residue which was re-crystallised from ethyl acetate. This afforded 10.5 g (56%) of 2-(piperazin-1-yl)benzothiazole-6-carbonitrile. A mixture of this piperazine derivative (19.4 g, 0.08 mol), sodium iodide (1.94 g), triethylamine (9.6 g, 0.095 mol) and DMF (80 mL) was heated with stirring to give a red liquid. A solution of 2-bromopropane (14.7 g, 0.12 mol) in DMF (80 mL) was added drop-wise at 117° C. within in 1 h. The reaction mixture was stirred at 110-117° C. for another 3 h and then allowed to cool to room temperature. Water (110 mL) was added and the mixture was filtered. The filter cake was washed until the filtrate was colourless and then dried. The solid was dissolved in DMF (250 mL) and filtered to remove a solid residue. Water (1000 mL) was added to the filtrate with stirring to give a precipitate. The solid was isolated, washed with water and dried to give 9.4 g (41%) of 2-(4-Isopropylpiperazin-1-yl)benzothiazole-6-carbonitrile.

Provenance & Evidence