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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Letter Article

Synthesis of trans N-Substituted Pyrrolidine Derivatives Bearing 1,2,4- triazole Ring

Author(s): Tangella Nagendra Prasad, Yeruva Pavankumar Reddy, Poorna Chandrasekhar Settipalli, Vadiga Shanthi Kumar, Eeda Koti Reddy, Shaik Firoj Basha and Shaik Anwar*

Volume 19, Issue 5, 2022

Published on: 08 April, 2022

Page: [578 - 582] Pages: 5

DOI: 10.2174/1570179419666211230094334

Price: $65

Abstract

Background: 1,2,4-triazoles scaffolds display significant biological activities due to hydrogen bonding, solubility, dipole character, and rigidity.

Objective: The core motif of 1,2,4-triazoles plays a vital role in clinical drugs such as Rizatriptan (antimigraine), Ribavirin (antiviral), anastrozole (anticancer), etizolam (anxiolytic), estazolam (anticonvulsant), alprazolam (anti-hypnotic), letrozole (aromatase inhibitor), loreclezole (anticonvulsant), trazadone (antidepressant) etc.

Methods: Epoxide ring opening of tert-butyl 6-oxa-3-azabicyclo [3.1.0] hexane-3-carboxylate followed by methylation under basic conditions and de-protection gave the corresponding trans 1-(4- methoxypyrrolidin-3-yl)-1H-1,2,4-triazole hydrochloride salt as the precursor. This precursor on reaction with substituted benzoyl chlorides and benzyl bromides gave the desired amide and amine products.

Results: A library of 14 N-substituted pyrrolidine derivatives i.e. trans3-methoxy-4-(1H-1,2,4-triazol- 1-yl) pyrrolidin-1-yl) (phenyl)methanone and trans 1-benzyl-4-methoxypyrrolidin-3-yl)-1H-1,2,4- triazole were prepared.

Conclusion: Eight novel amides (6a-h) and six amines (8a-f) derivatives were synthesized using 1-(4- methoxypyrrolidin-3-yl)-1H-1,2,4-triazole 4 salt with substituted benzoyl chlorides and benzyl bromides.

Keywords: Ring opening, epoxide, N-substituted pyrrolidine, trans-1-(4-methoxypyrrolidin-3-yl)-1H-1, 2, 4-triazole, trans 3- methoxy-4-(1H-1, 4-triazol-1-yl) pyrrolidin-1-yl) (phenyl) methanone, trans 1-(benzyl-4-methoxypyrrolidin-3-yl)-1H-1, 4- triazole.

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