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Successful utilization of \(\upbeta \)-ketonitrile in Biginelli reaction: synthesis of 5-cyanodihydropyrimidine

  • Sharad S Pachore
  • Narendra B Ambhaikar
  • Vidavalur Siddaiah
  • Sandip R Khobare
  • Sarvesh Kumar
  • Vilas H Dahanukar
  • U K Syam Kumar
Regular Article

Abstract

A Biginelli reaction of \(\upbeta \)-ketonitriles, aldehydes and urea in principle can yield 5-cyano substituted dihydropyrimidinones. Although potentially very useful, this substituted heterocycle is often difficult to synthesize via the three component reaction, presumably due to the lack of stability of \(\upbeta \)-ketonitriles. The present work describes the development of reaction conditions yielding the desired product. Interesting mechanistic observations have also been noted. Thirteen new compounds (derivatives) of 5-cyanodihydropyrimidin were synthesized.

GRAPHICAL ABSTRACT

Synopsis A straightforward and efficient multicomponent Biginelli reaction employing \(\upbeta \)-ketonitrile with aromatic or non-enolizable aliphatic aldehydes and urea in the presence of CuCl to cyano substituted dihydropyrimidones has been developed. A detailed study has been carried out to understand the reaction kinetics and an appropriate reaction mechanism has been proposed.

Keywords

Biginelli \(\upbeta \)-Ketonitrile dihydropyrimidin aldol aldehyde urea 

Notes

Acknowledgements

The authors would like to thank Dr. Upadhya Timmanna, Dr. Reddy’s Laboratories for the useful discussions and constant encouragement. We also thank Analytical department, Dr. Reddy’s Laboratories for providing the analytical support. (Dr. Reddy’s Laboratories IPDO IPM-00521).

Supplementary material

12039_2018_1467_MOESM1_ESM.pdf (1.2 mb)
Supplementary material 1 (pdf 1238 KB)

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Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  • Sharad S Pachore
    • 1
    • 2
  • Narendra B Ambhaikar
    • 1
  • Vidavalur Siddaiah
    • 2
  • Sandip R Khobare
    • 1
  • Sarvesh Kumar
    • 1
  • Vilas H Dahanukar
    • 1
  • U K Syam Kumar
    • 3
  1. 1.Integrated Product Development OrganizationDr. Reddy’s Laboratories Ltd.BachupallyIndia
  2. 2.Department of Organic Chemistry, Food, Drugs and WaterAndhra UniversityVisakhapatnamIndia
  3. 3.Research Center II, Aurobindo Pharmaceutical LimitedPashamylaram, HyderabadIndia

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