- Processes for the preparation of 5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrole
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This invention provides improved processes for the preparation of 5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrole, asenapine. These processes allow the preparation of asenapine at industrial scale in good yields and high stereoselectivity.
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- The syntheses of radiolabelled Org 5222 and its main metabolites Org 30526
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The syntheses of trans-5-chloro-2,3,3a-12b-tetrahydro-2-methyl-1H-dibenz [2,3:6,7]oxepino[4,5-c]pyrrole (Org 5222), a potential antipsychotic compound, labelled with 3H, 14C and 36C1 and trans-5-chloro-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7]-oxepino[4,5-c] pyrrole (Org 30526) labelled with 3H are described. 3H-labelled Org 5222 of low specific activity was prepared by a base catalyzed exchange with tritiated water of an amide precursor, 3H-labelled Org 5222 with a high specific activity by a catalytic reductive dehalogenation. 3H-labelled Org 30526 was prepared both by demethylation of 3H-Org 5222 and by catalytic reductive iodination of 11-iodo-Org 30526. 14C-labelled Org 5222 was synthesized in 6 steps using 14C-sarcosine as starting material. 36C1-labelled Org 5222 was prepared by diazotation reaction in the presence of H36C1.
- Vader,Kaspersen,Sperling,Schlachter,Terpstra,Hilberink,Wagenaars
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p. 845 - 869
(2007/10/02)
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- Biotransformation of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H- dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine maleate in rats
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The metabolism of trans-5-chloro-2-methyl-2,3,3a-12b-tetrahydro-1H- dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine maleate (Org 5222) labelled with [3H] or [14C] was investigated in Wistar rats. Metabolites were identified by mass spectrometry, 13C- and 1H-NMR analysis, IR spectroscopy and, wherever possible, by comparison with authentic reference compounds. The metabolites found in plasma, bile, faeces and urine revealed the processes of metabolism in which Org 5222 underwent oxidation to yield an N-oxide existing in two diastereoisomeric forms, or N-demethylation to yield a demethyl metabolite. A novel metabolite was found in bile viz. a carbamate glucuronide, formed from an intermediate carbamic acid, derived from the addition of CO2 to the demethyl metabolite.
- d. Wildenberg,Delbressine,Kaspersen,Wagenaars,Jacobs
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p. 540 - 544
(2007/10/02)
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