Parallel Synthesis of 1-Substituted
5-(5-Oxopyrrolidin-3-yl)-1H-pyrazole-4-carboxamides

Peter Perdih; Jernej Baškovč; Georg Dahmann; Uroš Grošelj; Drago Kočar; Ana Novak; Branko Stanovnik; Jurij Svete

doi:10.1055/s-0030-1261034

PAPER

Parallel Synthesis of 1-Substituted 5-(5-Oxopyrrolidin-3-yl)-1H-pyrazole-4-carboxamides

Peter Perdih^a, Jernej Baškovč^a, Georg Dahmann^b, Uroš Grošelj^a, Drago Kočar^a, Ana Novak^a, Branko Stanovnik^a, Jurij Svete*^a
^a Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, P.O. Box 537, 1000 Ljubljana, Slovenia
Fax: +386(1)2419220; e-Mail: Jurij.svete@fkkt.uni-lj.si;
^b Boehringer Ingelheim Pharma GmbH & Co. KG, Medicinal Chemistry, 88397 Biberach, Germany

Abstract

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Abstract

A parallel solution-phase synthesis of 5-(5-oxo-1-phenylpyrrolidin-3-yl)-1H-pyrazole-4-carboxamide derivatives as conformationally constrained pyrazole analogues of histamine starting from itaconic acid was developed. The synthetic method comprises a five-step preparation of 1-substituted 5-(5-oxo-1-phenylpyrrolidin-3-yl)-1H-pyrazole-4-carboxylic acids followed by parallel amidation with various primary and secondary amines to give a library of 24 histamine analogues in good overall yields and in very high purities. The method is general and substrate-independent. All the amidations proceed smoothly and no major difference in reactivity is observed with respect to the structures of the reactants.

Key words

pyrrolidinone - pyrazole - cyclocondensations - amidations - histamine analogues

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References

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