Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000084.xml
Synthesis 2013; 45(7): 919-924
DOI: 10.1055/s-0032-1318346
DOI: 10.1055/s-0032-1318346
paper
An Efficient Synthesis of 1-Methyl-4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]pyridine and Its N6-Substituted Analogues
Further Information
Publication History
Received: 08 November 2012
Accepted after revision: 12 February 2013
Publication Date:
27 February 2013 (online)
Abstract
An efficient synthesis of 1-methyl-4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]pyridine hydrochloride was achieved using simple sodium borohydride reduction of 6-benzyl-1-methyl-1H-pyrrolo[2,3-c]pyridin-6-ium bromide as the key step followed by its debenzylation with hydrogen over palladium on carbon on a multigram scale. Similarly, a series of N6-substituted 1-methyl-1H-pyrrolo[2,3-c]pyridin-6-ium halides were synthesized and reduced with sodium borohydride, showing this method to be applicable for the synthesis of different N6-substituted 1-methyl-4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]pyridines.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis.
- Supporting Information
-
References
- 1a Lovering F, Bikker J, Humblet C. J. Med. Chem. 2009; 52: 6752
- 1b Kingwell K. Nat. Rev. Drug Discovery 2009; 8: 931
- 2 van der Meijden MW, Leeman M, Gelens E, Noorduin WL, Meekes H, van Enckevort WJ. P, Kaptein B, Vlieg E, Kellogg RM. Org. Process Res. Dev. 2009; 13: 1195
- 3a Maffrand JP, Eloy F. Eur. J. Med. Chem. 1974; 9: 483
- 3b Satake K, Imai T, Kimura M, Morosawa S. Heterocycles 1981; 16: 1271
- 3c Aillaud I, Haurena C, Gall EL, Martens T, Ricci G. Molecules 2010; 15: 8144
- 4 Abou-Gharbia M, Patel UR, Webb MB, Moyer JA, Andree TH, Muth EA. J. Med. Chem. 1987; 30: 1818
- 5a Rousseau J.-F, Dodd RH. J. Org. Chem. 1998; 63: 2731
-
5b Bandini M, Melloni A, Piccinelli F, Sinisi R, Tommasi S, Umani-Ronchi A. J. Am. Chem. Soc. 2006; 128: 1424
- 6 Campbell SF, Kobylecki RJ. EP 186431, 1986 ; Chem. Abstr. 1986, 105, 153548.
- 7 Swinnen D, Bombrun A. WO 2006008303, 2006 ; Chem. Abstr. 2006, 144, 170972.
- 8a Mahadevan I, Rasmussen M. Tetrahedron 1993; 49: 7337
-
8b Van Baelen G, Hostyn S, Dhooghe L, Tapolcsányi P, Mátyus P, Lemière G, Dommisse R, Kaiser M, Brun R, Cos P, Maes L, Hajós G, Riedl Z, Nagy I, Maes BU. W, Pieters L. Bioorg. Med. Chem. 2009; 17: 7209
- 8c Huestis MP, Fagnou K. Org. Lett. 2009; 11: 1357
- 9 Nechayev MA, Gorobets NYu, Borisov AV, Kovalenko SM, Tolmachev AA. Mol. Divers. 2012; 16: 749
- 10 Jaramillo D, Liu Q, Aldrich-Wright J, Tor Y. J. Org. Chem. 2004; 69: 8151
- 11 It should be noted that application of benzyl chloride in such procedure is not recommended since the resulting chloride salt is highly hygroscopic.
- 12 The sp3-fraction is the number of sp3-hybridized carbons divided by the total carbon count; see ref. 1a for details.
Other multistep approaches for the synthesis of 4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]pyridine core apply synthetically available pyrrole-2/3-carbaldehydes as starting materials: