A Simplified Process for the Manufacture of Imagabalin Hydrochloride (PD-0332334), an alpha 2 delta-Ligand for the Treatment of Generalised Anxiety Disorder
The development of a highly efficient two-step process for the manufacture of the alpha 2 delta-ligand imagabalin hydrochloride 1 is described in 50% overall yield from (R)-3-methylhexanoic acid 2. Key aspects of this route include the development of a one-pot process for the synthesis of beta-enami...
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Published in | Organic process research & development Vol. 15; no. 6; pp. 1358 - 1364 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
Amer Chemical Soc
01.11.2011
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Subjects | |
Online Access | Get full text |
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Summary: | The development of a highly efficient two-step process for the manufacture of the alpha 2 delta-ligand imagabalin hydrochloride 1 is described in 50% overall yield from (R)-3-methylhexanoic acid 2. Key aspects of this route include the development of a one-pot process for the synthesis of beta-enamine ester 7 and its subsequent diastereoselective hydrogenation with a Ru-(S)-BINAP catalyst. The use of a combination of TFA, ammonium trifluoroacetate, and relatively low pressures in the asymmetric hydrogenation are novel conditions reported for this type of transformation. The simplified process described realised a 4-fold reduction in cost of goods compared with the previously described enabling route. |
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ISSN: | 1083-6160 |
DOI: | 10.1021/op2002326 |