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. 2008:4:20.
doi: 10.3762/bjoc.4.20. Epub 2008 Jun 12.

Synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile: a key intermediate for dipeptidyl peptidase IV inhibitors

Santosh Kumar Singh  1 , Narendra Manne, Manojit Pal
Affiliations

Synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile: a key intermediate for dipeptidyl peptidase IV inhibitors

Santosh Kumar Singh et al. Beilstein J Org Chem. 2008.

Abstract

An alternative and practical synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile was achieved. Reaction of L-proline with chloroacetyl chloride was followed by conversion of the carboxylic acid moiety of the resulting N-acylated product into the carbonitrile via the corresponding amide intermediate. The synthesized pyrrolidine derivative was utilized to prepare DPP-IV inhibitor Vildagliptin.

Keywords: 2(S)-cyanopyrrolidine; DPP-IV inhibitors; L-proline; N-acylation; amides.

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Figures

Figure 1
Figure 1
DPP-IV Inhibitors.
Figure 2
Figure 2
Role of 2(S)-cyanopyrrolidine moiety in DPP-IV inhibition.
Scheme 1
Scheme 1
Earlier route to (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile (6).
Scheme 2
Scheme 2
Synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile (6).
Scheme 3
Scheme 3
Preparation of Vildagliptin (2).
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References

    1. Deacon C F, Holst J J. Int J Biochem Cell Biol. 2006;38:831–844. doi: 10.1016/j.biocel.2005.09.011. - DOI - PubMed
    1. Mest H-J. Curr Opin Invest Drugs. 2006;7:338–343. - PubMed
    1. McIntosh C H S, Demuth H-U, Kim S-J, Pospisilik J A, Pederson R A. Int J Biochem Cell Biol. 2006;38:860–872. doi: 10.1016/j.biocel.2005.12.013. - DOI - PubMed
    1. Villhauer E B, Brinkman J A, Naderi G B, Dunning B E, Mangold B L, Mone M D, Russel M E, Weldon S C, Hughes T E. J Med Chem. 2002;45:2362–2365. doi: 10.1021/jm025522z. - DOI - PubMed
    1. Ahrén B, Simonsson E, Larson H, Landin-Olsson M, Torgeirsson H, Jansson P-A, Sandqvist M, Båvenholm P, Efendic S, Eriksson J W, et al. Diabetes Care. 2002;25:869–875. doi: 10.2337/diacare.25.5.869. - DOI - PubMed

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