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 |
|---|---|
| Journal | European Journal of Organic Chemistry |
| DOIs | |
| Publication status | Published - 1 Jan 2019 |
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Keywords
- Argatroban
- Multicomponent reactions
- Pharmaceuticals
- Pipecolic amides
- Stereoselectivity
Cite this
}
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, 01.01.2019.Research output: Contribution to Journal › Article › Academic › peer-review
TY - JOUR
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.
PY - 2019/1/1
Y1 - 2019/1/1
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
UR - http://www.scopus.com/inward/record.url?scp=85066616787&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066616787&partnerID=8YFLogxK
U2 - 10.1002/ejoc.201900399
DO - 10.1002/ejoc.201900399
M3 - Article
JO - European Journal of Organic Chemistry
JF - European Journal of Organic Chemistry
SN - 1434-193X
ER -