Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides

Gydo van der Heijden; Timo B. van Schaik; Valentinos Mouarrawis; Martin J.M. de Wit; Christophe M.L.Vande Velde; Eelco Ruijter; Romano V.A. Orru

doi:10.1002/ejoc.201900399

Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides

Gydo van der Heijden, Timo B. van Schaik, Valentinos Mouarrawis, Martin J.M. de Wit, Christophe M.L.Vande Velde, Eelco Ruijter^*, Romano V.A. Orru

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

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Abstract

An efficient Ugi-type three-component reaction (U-3CR) for the synthesis of pipecolic amides is reported. The U-3CR between electronically diverse isocyanides, carboxylic acids and 4-substituted Δ1-piperideines proceeds in a highly diastereoselective fashion. The Δ1-piperideines are obtained by NCS-mediated oxidation of the corresponding 4-substituted piperidines, which in turn are generated by an efficient two-step procedure involving the alkylation of 4-picoline and subsequent catalytic hydrogenation of the pyridine ring. We demonstrate the utility of this U-3CR, in combination with the convertible isocyanide 2-bromo-6-isocyanopyridine, in the synthesis of the anticoagulant argatroban.

Original language	English
Pages (from-to)	5313-5325
Number of pages	13
Journal	European Journal of Organic Chemistry
Volume	2019
Issue number	31-32
Early online date	25 Apr 2019
DOIs	https://doi.org/10.1002/ejoc.201900399
Publication status	Published - 1 Sep 2019

Bibliographical note

Special Issue: Heterocyclic Chemistry

Keywords

Argatroban
Multicomponent reactions
Pharmaceuticals
Pipecolic amides
Stereoselectivity

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10.1002/ejoc.201900399

Efficient Diastereoselective Three-Component Synthesis of Pipecolic AmidesFinal published version, 2.57 MBLicence: Article 25fa Dutch Copyright Act

CCDC 1910686: Experimental Crystal Structure Determination
van der Heijden, G. (Contributor), van Schaik, T. (Contributor), Mouarrawis, V. (Contributor), de Wit, M. (Contributor), Velde, C. V. (Contributor), Ruijter, E. (Contributor) & Orru, R. (Contributor), Unknown Publisher, 1 Jan 2019
DOI: 10.5517/ccdc.csd.cc22471j, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc22471j&sid=DataCite
Dataset

Cite this

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title = "Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides",

abstract = "An efficient Ugi-type three-component reaction (U-3CR) for the synthesis of pipecolic amides is reported. The U-3CR between electronically diverse isocyanides, carboxylic acids and 4-substituted Δ1-piperideines proceeds in a highly diastereoselective fashion. The Δ1-piperideines are obtained by NCS-mediated oxidation of the corresponding 4-substituted piperidines, which in turn are generated by an efficient two-step procedure involving the alkylation of 4-picoline and subsequent catalytic hydrogenation of the pyridine ring. We demonstrate the utility of this U-3CR, in combination with the convertible isocyanide 2-bromo-6-isocyanopyridine, in the synthesis of the anticoagulant argatroban.",

keywords = "Argatroban, Multicomponent reactions, Pharmaceuticals, Pipecolic amides, Stereoselectivity",

author = "{van der Heijden}, Gydo and {van Schaik}, {Timo B.} and Valentinos Mouarrawis and {de Wit}, {Martin J.M.} and Velde, {Christophe M.L.Vande} and Eelco Ruijter and Orru, {Romano V.A.}",

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language = "English",

volume = "2019",

pages = "5313--5325",

journal = "European Journal of Organic Chemistry",

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Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides. / van der Heijden, Gydo; van Schaik, Timo B.; Mouarrawis, Valentinos; de Wit, Martin J.M.; Velde, Christophe M.L.Vande; Ruijter, Eelco ; Orru, Romano V.A.

In: European Journal of Organic Chemistry, Vol. 2019, No. 31-32, 01.09.2019, p. 5313-5325.

Research output: Contribution to Journal › Article › Academic › peer-review

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T1 - Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides

AU - van der Heijden, Gydo

AU - van Schaik, Timo B.

AU - Mouarrawis, Valentinos

AU - de Wit, Martin J.M.

AU - Velde, Christophe M.L.Vande

AU - Ruijter, Eelco

AU - Orru, Romano V.A.

N1 - Special Issue: Heterocyclic Chemistry

PY - 2019/9/1

Y1 - 2019/9/1

N2 - An efficient Ugi-type three-component reaction (U-3CR) for the synthesis of pipecolic amides is reported. The U-3CR between electronically diverse isocyanides, carboxylic acids and 4-substituted Δ1-piperideines proceeds in a highly diastereoselective fashion. The Δ1-piperideines are obtained by NCS-mediated oxidation of the corresponding 4-substituted piperidines, which in turn are generated by an efficient two-step procedure involving the alkylation of 4-picoline and subsequent catalytic hydrogenation of the pyridine ring. We demonstrate the utility of this U-3CR, in combination with the convertible isocyanide 2-bromo-6-isocyanopyridine, in the synthesis of the anticoagulant argatroban.

AB - An efficient Ugi-type three-component reaction (U-3CR) for the synthesis of pipecolic amides is reported. The U-3CR between electronically diverse isocyanides, carboxylic acids and 4-substituted Δ1-piperideines proceeds in a highly diastereoselective fashion. The Δ1-piperideines are obtained by NCS-mediated oxidation of the corresponding 4-substituted piperidines, which in turn are generated by an efficient two-step procedure involving the alkylation of 4-picoline and subsequent catalytic hydrogenation of the pyridine ring. We demonstrate the utility of this U-3CR, in combination with the convertible isocyanide 2-bromo-6-isocyanopyridine, in the synthesis of the anticoagulant argatroban.

KW - Argatroban

KW - Multicomponent reactions

KW - Pharmaceuticals

KW - Pipecolic amides

KW - Stereoselectivity

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ER -

Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides

Abstract

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Datasets

CCDC 1910686: Experimental Crystal Structure Determination

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