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

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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.

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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).

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Authors and Affiliations

  1. Integrated Product Development Organization, Dr. Reddy’s Laboratories Ltd., Innovation Plaza, Bachupally, Telangana, 500 072, India

    Sharad S Pachore, Narendra B Ambhaikar, Sandip R Khobare, Sarvesh Kumar & Vilas H Dahanukar

  2. Department of Organic Chemistry, Food, Drugs and Water, Andhra University, Visakhapatnam, Andhra Pradesh, 530 003, India

    Sharad S Pachore & Vidavalur Siddaiah

  3. Research Center II, Aurobindo Pharmaceutical Limited, Pashamylaram, Hyderabad, Telangana, 502 307, India

    U K Syam Kumar

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  1. Sharad S Pachore
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Special Section on Transition Metal Catalyzed Synthesis of Medicinally Relevant Molecules.

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Pachore, S.S., Ambhaikar, N.B., Siddaiah, V. et al. Successful utilization of \(\upbeta \)-ketonitrile in Biginelli reaction: synthesis of 5-cyanodihydropyrimidine. J Chem Sci 130, 69 (2018). https://doi.org/10.1007/s12039-018-1467-7

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