p-Toluenesulfonic acid → Cyclopropanecarboxamide, N-((4-((8-chloro-4,10-dihydro-1-methylpyrazolo(3,4-b)(1,5)benzodiazepin-5(1H)-yl)carbonyl)-2-fluorophenyl)methyl)-, 4-methylbenzenesulfonate

Participants

Reaction Conditions

Reaction Steps

The tosylate salt of the present invention may be prepared as follows: A mixture of cyclopropanecarboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraazabenzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide (prepared by the method described in PCT/DK2005/000540) and para-toluenesulphonic acid are combined in a suitable solvent (e.g. methanol) and stirred at a suitable temperature (e.g. 20 to 25° C.) for a period of time (e.g. 6 to 24 hours). The solvent is then removed (e.g. by rotary evaporation). The dried material may then be suspended in a suitable solvent (e.g. t-butyl methyl ether) and then sonicated for a suitable time (e.g. 2 to 6 hours) at a suitable temperature (e.g. 50 to 70° C.). The solids may then be collected (e.g. by centrifugation) and dried under vacuum to yield cyclopropanecarboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraazabenzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide para-toluenesulphonate in amorphous form.

Provenance & Evidence