A facile access to 2-ethynyl-1,4-dihydropyridines via Hantzsch three-component reaction

Heterocycles

Volumn 59, Issue 2, 2003, Pages 779-783

  Szemes Jr , Fridrich ^a   Marchalín, Štefan ^a   Prónayová, Nadežda ^a   Daïch, Adam ^b  

^a SLOVAK UNIVERSITY OF TECHNOLOGY   (Slovakia)

^b UNIVERSITÉ DU HAVRE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

2 ETHYNYL 1,4 DIHYDROPYRIDINE DERIVATIVE; 3 [[4 [[4 (AMINOIMINOMETHYL)PHENYL]AMINO] 1,4 DIOXOBUTYL]AMINO] 4 PENTYNOIC ACID; ANTITHROMBOCYTIC AGENT; DIHYDROPYRIDINE DERIVATIVE; PRODRUG; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; CORONARY ARTERY BLOOD FLOW; CYCLIZATION; DRUG SYNTHESIS; HYDROLYSIS; THROMBOCYTE AGGREGATION INHIBITION;

EID: 0037344686     PISSN: 03855414     EISSN: None     Source Type: Journal    
DOI: 10.3987/com-02-s69     Document Type: Article

References (22)

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3. 2 which resembles a nitrile one (see the calcium modulators Nilvadipine family) in terms of electronic structure and also in sterical bulkiness. In contrary the 2-vinyl-, 2-acetyl- and 2-formyl-1,4-DHP derivatives were all inactive.
4. E. J. Corey and P. L. Fuchs, Tetrahedron Lett., 1972, 3769.
5. 4) was obtained in 4 or 5 steps from 2-chlorobenzaldehyde (4) according to the Hantzsch type cyclocondensation followed by the Corey's method.
6. 4-position of the DHP ring, proved the Corey's approach to homologous of 3 more difficult, associated with lower yield, not reproducible and finally unsuccessful.
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12. (f) Š. Marchalín, M. Chudík, K. Cvopová, J. Kožíšek, J. Leško, and A. Daïch, Tetrahedron, 2002, 58, 5747.
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15. For the Claisen condensation protocol, see the following reference: H. H. Wasserman, R. Frechette, T. Oida, and J. H. Van Duzer, J. Org. Chem., 1989, 54, 6012.
16. To our surprise, this compound (11a) was only briefly mentioned in the literature and was obtained by condensation of methyl lithioacetate with ethyl propiolate instead methyl propiolate used in our case. For this end see the following article: M. H. Ansari, T. Kusumoto, and T. Hiyama, Tetrahedron Lett., 1993, 34, 8271.
17. (a) Compound (11b) (R = Et) was prepared also from ethyl propiolate in an excellent yield of 95% (bp=83-85°C/2 mm Hg). For this end, see ref. 1.
18. 3Si).
19. No indication has been done in the literature concerning such keto-enol tautomerism in these γ-ethynyl-β-keto ester products.
20. The use of 3-nitrobenzaldehyde instead 2-chlorobenzaldehyde was chosen to test the feasibility of our approach in comparison to the Corey's one which was unsuccessfully with this formyl substrate.
21. 6: C, 60.67; H, 4.53; N, 7.86. Found: C, 60.60; H, 4.40; N, 8.02.
22. The olefin geometry of products (17c-e) was established as E according to the NOE Difference experiments.