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How would I synthesise LY-293,284?

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Figure 1: LY-293,284

I have satisfied the conditions at the page Should we allow Synthesis questions subject to the six constraints listed below? so please don't just write off this question and close it. The constraints are satisfied as followed:

  • Starter material(s): 5-acetylindole.

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Figure 2: 5-acetylindole

  • I have completed a Google search to check for LY-293,284 synthesis pathways by typing "LY-293,284 synthesis" and there were no applicable results.

  • I would imagine the synthesis would occur via the following pathways:

    • Phenylation of the 5-acetylindole to phenyl-5-acetylindole.
    • Oxidation of the resulting phenyl-5-acetylindole with oxidising agents such as potassium nitrate?
    • Di-n-propylamination of the resulting 5-acetylindolylphenol with di-n-propylamine to LY-293,284.
  • The synthesis I'm hoping is simple.

  • LY-293,284 is a 5-HT1A receptor full agonist.
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  • $\begingroup$ I think you'd want to start from 5-acetylindole $\endgroup$ – Richard Terrett Feb 7 '13 at 23:44
  • $\begingroup$ This is 5-acetylindole: i.imgur.com/Qc6W49d.gif $\endgroup$ – Brian Feb 8 '13 at 1:44
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If you look at Eli Lilly patents and other literature, there doesn't seem to be a simple synthesis... I've put together an example of how it could be done. Although there are many ways you could go depending on starting materials, this way is based primarily on literature reactions with the exception of the last 3 steps which are Eli Lilly patents. I stopped after about 16 steps as I think that's more than enough to demonstrate how complex these designer molecule syntheses can be. I also left out reagents/reaction conditions just to show the general pathway, and to save on eye strain.

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So really the simplicity (or complexity) will depend on where you are able to start on the synthetic pathway (e.g. what starting materials are available to you).

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