A Practical Approach for the Synthesis of Novel Triazolo-fused Benzazepine Derivatives Using a Multi-component Reaction and an Intramolecular C–H Arylation

An efficient and straightforward method has been developed for the preparation of triazolo-fused benzazepines by a facile, one-pot Ugi multi-component reaction/click reaction. In this strategy, the Ugi-reaction products were coupled by a click reaction, thus integrating the triazole fragment into the benzazepine structure using an intramolecular C–H arylation. The corresponding products were obtained in good yields without unfavourable by-products.

[1]  A. Natu,et al.  Convenient Syntheses of 3-Aryl-3,4-Dihydroisocoumarins , 2015 .

[2]  A. Shafiee,et al.  Synthesis of novel fused 4,5-dihydro-1,2,3-triazolo[1,5-a][1,4]benzodiazepine derivatives via four-component Ugi–Smiles-type reaction , 2013 .

[3]  L. Ackermann,et al.  Copper-catalyzed CuAAC/intramolecular C–H arylation sequence: Synthesis of annulated 1,2,3-triazoles , 2012, Beilstein journal of organic chemistry.

[4]  K. Swamy,et al.  Facile Construction of [6,6]-, [6,7]-, [6,8]-, and [6,9]Ring-Fused Triazole Frameworks by Copper-Catalyzed, Tandem, One-Pot, Click and Intramolecular Arylation Reactions: Elaboration to Fused Pentacyclic Derivatives , 2012 .

[5]  Yong Xu,et al.  Design, synthesis, and in vitro biological evaluation of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents targeting virus nucleoprotein. , 2012, Journal of medicinal chemistry.

[6]  C. Cai,et al.  A One‐Pot Tandem Ugi Multicomponent Reaction (MCR)/Click Reaction as an Efficient Protecting‐Group‐Free Route to 1H‐1,2,3‐Triazole‐Modified α‐Amino Acid Derivatives and Peptidomimetics , 2012 .

[7]  M. Botta,et al.  Synthesis, biological evaluation and molecular modeling of 1,2,3-triazole analogs of combretastatin A-1. , 2012, Bioorganic & medicinal chemistry.

[8]  Â. Pinto,et al.  Novel 1,2,3-triazole derivatives for use against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain. , 2011, Journal of medicinal chemistry.

[9]  J. Gestwicki,et al.  Improved synthesis of 15-deoxyspergualin analogs using the Ugi multi-component reaction. , 2011, Bioorganic & medicinal chemistry letters.

[10]  Jingshing Wu,et al.  Unexpected synthesis of indolo[1,2-c]quinazolines by a sequential Ugi 4CC-Staudinger-aza-Wittig-nucleophilic addition reaction. , 2011, Organic & biomolecular chemistry.

[11]  G. Krishna,et al.  Efficient catalyst-free Domino approach for the synthesis of novel 2-benzazepine derivatives in water , 2010 .

[12]  J. Iqbal,et al.  An efficient synthesis of varenicline , 2010 .

[13]  H. Castro,et al.  Synthesis, antiplatelet and in silico evaluations of novel N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides. , 2009, Bioorganic & medicinal chemistry.

[14]  Brian M. Smith,et al.  Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity. , 2008, Journal of medicinal chemistry.

[15]  Jiling. Huang,et al.  Formal synthesis of the ACE inhibitor benazepril x HCl via an asymmetric aza-Michael reaction. , 2006, Molecules.

[16]  V. A. Kovtunenko,et al.  Synthesis and properties of new functionalized 2-benzazepines , 2006 .

[17]  I. Akritopoulou‐Zanze,et al.  A versatile synthesis of fused triazolo derivatives by sequential Ugi/alkyne-azide cycloaddition reactions , 2004 .

[18]  C. Hulme,et al.  "Multi-component reactions : emerging chemistry in drug discovery" 'from xylocain to crixivan'. , 2003, Current medicinal chemistry.

[19]  I. Ugi,et al.  Multicomponent Reactions with Isocyanides. , 2000, Angewandte Chemie.

[20]  Joel Morris,et al.  Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. , 2000, Journal of medicinal chemistry.

[21]  E. De Clercq,et al.  1,2,3-Triazole-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D- ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"-oxathiole 2",2"-dioxide) (TSAO) analogues: synthesis and anti-HIV-1 activity. , 1994, Journal of medicinal chemistry.

[22]  D. Buckle,et al.  Studies on 1,2,3-triazoles. 13. (Piperazinylalkoxy) [1]benzopyrano[2,3-d]-1,2,3-triazol-9(1H)-ones with combined H1-antihistamine and mast cell stabilizing properties. , 1986, Journal of medicinal chemistry.

[23]  H. Sarau,et al.  Synthesis and renal vasodilator activity of some dopamine agonist 1-aryl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diols: halogen and methyl analogues of fenoldopam. , 1986, Journal of medicinal chemistry.

[24]  R. Huisgen.  1.3‐Dipolare Cycloadditionen Rückschau und Ausblick , 1963 .