O-Xylene → 4-(4-Methyl-4H-thieno[3,4-b][1,5]benzodiazepin-10-yl)-1-piperazineethanol hemifumarate

Participants

Reaction Steps

A mixture comprising 2.6 g. of 4-methyl-10-(methylthio)-4H-thieno[3,4-b][1,5]benzodiazepine (U.S. Pat. No. 3,951,981 -- Ex. 7), 2.6 g. of hydroxyethylpiperazine, 3 drops of acetic acid and 15 ml. of xylene is stirred and refluxed overnight. The mixture is evaporated, washed with water and the residue dissolved in 50 ml. of 2N acetic acid. The solution is filtered. The filtrate is made alkaline with ammonium hydroxide and extracted with chloroform. The extract is dried over magnesium sulfate, filtered and evaporated giving a dark colored oil. This oil is dissolved in 20 ml. of ethanol. A mixture of 1.2 g. of fumaric acid in 25 ml. of ethanol is added and on standing a yellow solid separates. This solid is recrystallized from 75 ml. of ethanol giving the desired product, m.p. 192°-193° C. as the fumarate salt.

Provenance & Evidence