多组分反应英文文献

L -Proline-catalyzed

three-component domino reactions for the

synthesis of highly functionalized pyrazolo[3,4-b

]pyridines

Pethaiah Gunasekaran,Pitchaimani Prasanna,Subbu Perumal ⇑

Department of Organic Chemistry,School of Chemistry,Madurai Kamaraj University,Madurai 625021,India

a r t i c l e i n f o Article history:

Received 2October 2013Revised 2November 2013Accepted 5November 2013

Available online 14November 2013Keywords:

Three-component,domino reactions

3-Methyl-1-aryl -1H-pyrazol-5-amines,N -methyl-1-(methylthio)-2-nitroprop-1-en-1-amine

Pyrazolo[3,4-b ]pyridines L -Proline

a b s t r a c t

A series of novel N ,3-dimethyl-5-nitro-1-aryl-1H -pyrazolo[3,4-b ]pyridin-6-amines was obtained in good yields from the domino reactions of N -methyl-1-(methylthio)-2-nitroprop-1-en-1-amine,aromatic alde-hydes,and 3-methyl-1-aryl -1H-pyrazol-5-amines in ethanol in the presence of green catalyst,L -proline.This transformation involves the formation of two C–C and one C–N bonds leading to the creation of a six-membered ring in a one-pot operation.

Ó2013Elsevier Ltd.All rights reserved.

The pyrazolo[3,4-b ]pyridine ring system has emerged as an important scaffold in pharmaceutical arena in view of its occur-rence as bio-active drug targets and numerous biologically active compounds.1These compounds display diverse biological activities such as antiviral,2anti-inflammatory,3anxiolytic,4hypoglycemic,5antitumor,6herbicidal,7antiherpetic,and antiallergic.8They also act as serotonin reuptake inhibitors,9CCK agonists,10vasodila-tors,11potent cyclin dependent kinase 1inhibitor,12HIV reverse transcriptase inhibitors,13CCR1antagonists,14and protein kinase inhibitors.15Some notable pyrazolo[3,4-b ]pyridine embedded het-erocycles are the anxiolytic drugs 16such as cartazolate,etazolate,and tracazolate (Fig.1),the cardiovascular therapeutic agent,BAY 41-2272,17and the GSK-3inhibitor,efficacious in the treatment of Alzheimer’s disease.In addition to the biological importance,their structural similitude to purine base,an important constituent of DNA and RNA nucleosides,18is an added attraction for the inter-est in the synthesis of pyrazolo[3,4-b ]pyridines.

The synthetic protocols reported earlier for pyrazolo[3,4-b ]pyr-idines include multi-component reaction of pyrazolamines (a)with isatin and cyclic diketones in the presence of CAN catalyst,19(b)with salicylaldehyde and ethyl acetoacetate in the presence of piperidine and acetic acid,20(c)with electron-deficient alkenes,isoflavones,and coumarinaldehydes,21(d)bearing the benzotriaz-olymethyl group at 4-position/amino nitrogen with unactivated and electron-rich alkenes in the presence of p -TSA followed by het-erocyclization.22They have also been obtained from (i)the reaction of indolin-2-one,3-oxo-3-phenylpropanenitrile,hydrazines,and aldehydes in ionic liquid,[bmim]Br,and p -TSA catalyst,23(ii)het-ero Diels–Alder reactions of azadienes with alkynes and alkenes,24(iii)transformations using substituted pyridines as starting materi-als in two or more steps,25and (iii)condensation of 3-carbonitrile-

0040-4039/$-see front matter Ó2013Elsevier Ltd.All rights reserved./10.1016/j.tetlet.2013.11.016

Corresponding author.Tel./fax:+914522459845.

E-mail address:subbu.perum@ (S.Perumal).