1012884-46-6Relevant articles and documents
PROCESS FOR THE PREPARATION OF ASENAPINE MALEATE
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Paragraph 0053, (2015/04/28)
The present invention provides a process for the preparation of asenapine maleate of Formula (I), comprising: intra-molecular cyclization of the intermediate of Formula (II) to obtain the intermediate of Formula (III) using aluminium halide.
Debottlenecking the Synthesis Route of Asenapine
Van Der Linden, Marco,Roeters, Theo,Harling, Ramon,Stokkingreef, Edwin,Gelpke, Arjan Sollewijn,Kemperman, Gerjan
, p. 196 - 201 (2013/01/03)
The discovery synthesis of asenapine that was used for the manufacture of drug substance batches up to 10 kg contained two chemical steps that were major bottlenecks for scale-up. One of these steps involved a magnesium/methanol reduction of an enamide moiety that was severely hampered by safety and efficiency problems. The other step was a laborious chromatography and isomerization cycle that was marked by a poor yield and extremely low throughput The safety issues of the magnesium/methanol reduction could be solved by adding portions of magnesium to a solution of the enamide. In addition, an alternative process for the conversion of the mixture of cis- and trans-lactam into the desired trans-isomer was developed, circumventing the chromatographic separation.