page_title: JNJ-7925476
section_title: Chemistry
hierarchical_section_title: JNJ-7925476 / Chemistry
caption_attribution_description: English: Summary of main reactions to make certain Pyrroloisoquinoline compounds.
context_page_description: JNJ-7925476 is a triple reuptake inhibitor antidepressant discovered by Johnson & Johnson, but never marketed.
  These molecules were first prepared by Bruce E. Maryanoff and coworkers during the late 1970s–1980s. The structure is a pyrroloisoquinoline core, with an overlaid benzhydryl motif.
  Incorporating the pyrrolidino ring onto the tetrahydroisoquinoline scaffolding markedly improves potency, although this only works for one of the available stereoisomers. JNJ-7925476 is a racemic preparation of the more potent diastereomer. Of these enantiomers, the eutomer is the stereoisomer, known as JNJ-39836966, and the distomer, is JNJ-39836732
  There is some confusion over the nomenclature and cis/trans isomeric relationship at the piperidine ring. The compounds as depicted have the carbon of the pyrrolidine carbon and the phenyl cis, but Maryanoff and coworkers are of the opinion that the compound is trans.
  The reason for this is not known because it was referred to as "cis" in earlier reports, and then later reassigned.
context_section_description: The N-acyliminium cyclization route; and the mandelic acid and styrene oxide route were employed for most of the target compounds.
  The SS/RR diastereomers as the principle products if one follows the above steps.
  It is possible to epimerize the product to the desired RS/SR diastereomers, but the equilibrium is only 50/50.
  Hence, alternative synthetic methods needed to be sought to obtain the desired isomer/s in diastereochemical excess.
  If instead of an "aryl" group, a tert-butyl or a cyclohexyl was used, then it was possible to alter the stereochemical discourse of the reaction.
caption: Pyrroloisoquinoline Synthesis
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