Methanesulfonic Acid → 5,11-Dihydro-11-(((2-(2-((dipropylamino)methyl)-1-piperidinyl)ethyl)amino)carbonyl)-6H-pyrido(2,3-b)(1,4)-benzodiazepin-6-one methanesulfonate

Participants

Reaction Conditions

Reaction Steps

To a suspension of 56.2 g (0.1174 mol) of 5,11-dihydro-11-[[[2-[2-[(dipropylamino)methyl]-piperidin-1-yl]ethyl]amino]carbonyl]-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one in a mixture of 100 ml of acetonitrile and 100 ml of ethyl acetate, a solution of 11.3 g (0.1176 mol) of methanesulphonic acid in 74 ml of acetonitrile was added dropwise whilst cooling with ice and stirring. After removal of the ice bath the mixture was heated to 70° C., 574 ml of acetic acid were added dropwise to the now clear solution, the mixture was inoculated with a crystal of the desired salt, left to cool to 40° C. and stirred for 2 hours at this temperature, then heated up to 50° C., 280 ml of ethyl acetate were again slowly added dropwise and after removal of the heating bath the mixture was stirred for 2 hours at ambient temperature, left to stand for 14 hours and finally the crystals formed were suction filtered. After washing with ethyl acetate and drying in a circulating air dryer, 64.0 g (95% of theory) of colourless crystals were obtained, m.p. 165°-167° C.

Provenance & Evidence