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Synfacts 2012; 8(2): 0121
DOI: 10.1055/s-0031-1289963
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of a Precursor to LY2140023

Autoren

    Rezensent(en):

  • Philip Kocienski

Waser M, * Moher ED et al.. * DSM Fine Chemicals Austria Nfg GmbH & Co KG, Linz, Austria and Eli Lilly and Company, Indianapolis, USA
Process Development for a Key Synthetic Intermediate of LY2140023, a Clinical Candidate for the Treatment of Schizophrenia.

Org. Process Res. Dev. 2011;
15: 1266-1274
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Publikationsverlauf

Publikationsdatum:
19. Januar 2012 (online)

 
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Key words

LY2140023 - mGlu2/3 receptor agonist - cyclopropanation - Bucherer–Bergs reaction

Significance

LY2140023 is a conformationally restricted glutamic acid analogue that is an mGlu2/3 receptor agonist. It entered phase II clinical trials for the treatment of schizophrenia. The following synthesis was used to deliver over one metric ton of the key intermediate K.


Comment

Whilst the later steps are described on large scale, the earlier steps, especially the critical carbene insertion reaction leading to cyclopropane B, is reported on a small scale. A large-scale (206 mol) hydroboration of B using BH3·THF complex is described.





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