Synthesis of some tetrazole fused pyrido[2,3-c]coumarin derivatives from a one-pot three-component reaction via intramolecular 1,3-dipolar cycloaddition reaction of azide to nitriles Pallabi Borah, P. Seetham Naidu, Pulak J. Bhuyan ⇑ Medicinal Chemistry Division, CSIR-North East Institute of Science Technology, Jorhat 785006, Assam, India article info Article history: Received 11 June 2012 Revised 11 July 2012 Accepted 13 July 2012 Available online 20 July 2012 Keywords: Pyrido[2,3-c]coumarin Tetrazole Multi-component reactions (MCRs) Azides Nitriles abstract Some novel tetrazole fused pyrido[2,3-c]coumarin derivatives 5/7/9 were synthesized from a one-pot three-component reaction of 4-chloro-3-formylcoumarins 2, sodium azide 3, and alkyl/aryl acetonitriles 4/6/8. Ó 2012 Elsevier Ltd. All rights reserved. Coumarins are an important class of compounds obtained from both nature and synthetic origin that possess diverse pharmaceu- tical and biological activities, often depending on the substituent they bear in the parent benzopyran moiety. 1 As for instance, ben- zopyranone-pyridine or piperidines interact with DNA, 2 for energy transfer in photophysical processes, 3 to act as potential platelet activating factor antagonists, 4 to be depressant or hypotensive activators 5 and potent antipsychotic agents. 6 Some of their repre- sentatives exhibit antibacterial, 7 antitumor, 8 anticholinergic, 9 and antimicrobial 10 activities. Pyridine annelated coumarins also show antiallergic, anticoagulant, antidiabetic, and analgesic properties. 11 Similarly, imidazolo–coumarins act as CNS depressant, mamma- lian cancer growth inhibitor, and also as phosphor-diesterase VII inhibitors for the treatment of immunity associated diseases. 12 Notably, most of these bioactive compounds are fused 3,4-hetero- cyclic coumarin derivatives. Therefore, considerable efforts have been made toward the synthetic manipulation of coumarins to find more useful compounds. As a result of this effort a number of ann- elated coumarin derivatives have been obtained with diverse bio- logical activities. 13 Tetrazoles are an important class of compounds which have been the subject of intensive research and applied investigations. 14 Tetrazoles are regarded as biologically equivalent to the carboxylic acid group. 15 Both carboxylic acid and tetrazoles act as ligand binding functionality for CYP450-derived oxidative metabolic pro- cesses, and tetrazoles have the advantage over carboxylic acids in terms of escaping most bio-transformations by Phase-II reaction pathways. 16 1H- and 2H-tetrazoles are frequently employed in O O OH DMF + POCl 3 O O Cl CHO 1 2 O O Cl CHO 2 NaN 3 R 1 CH 2 CN O O 5a-c N N N N R 1 O O Cl CHO 2 R 2 O CN O O N N N N 3 4a-c 3 6a-d. (R 2 = aryl) OR 8a-c. (R 2 = indolyl) R 1 = CONH 2 , CO 2 Et, CN + + + + O O N N N N R 1 7a-d. (R 2 = aryl) OR 9a-c. (R 2 = indolyl) R 2 O NaN 3 Scheme 1. 0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetlet.2012.07.060 ⇑ Corresponding author. Tel.: +91 376 2370121; fax: +91 376 2370011. E-mail address: pulak_jyoti@yahoo.com (P.J. Bhuyan). Tetrahedron Letters 53 (2012) 5034–5037 Contents lists available at SciVerse ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet