A Unified Continuous Flow Assembly-Line Synthesis of Highly Substituted Pyrazoles and Pyrazolines
Name
A Unified Continuous Flow Assembly Line Synthesis of Highly Substituted Pyrazoles and Pyrazolines .pdf
Size
1.85 MB
Format
Adobe PDF
Checksum (MD5)
63b3c017b465cd964745dd90eb27a0ab
Author(s)
Britton, Joshua
Jamison, Timothy F
Date Issued
July 2017
Journal
Angewandte Chemie International Edition
Publisher
Wiley Blackwell
Citation
Britton, Joshua and Timothy F. Jamison. “A Unified Continuous Flow Assembly-Line Synthesis of Highly Substituted Pyrazoles and Pyrazolines.” Angewandte Chemie International Edition 56, 30 (June 2017): 8823–8827 © 2017 Wiley‐VCH Verlag GmbH & Co
Version
Author's final manuscript
Abstract
A rapid and modular continuous flow synthesis of highly functionalized fluorinated pyrazoles and pyrazolines has been developed. Flowing fluorinated amines through sequential reactor coils mediates diazoalkane formation and [3+2] cycloaddition to generate more than 30 azoles in a telescoped fashion. Pyrazole cores are then sequentially modified through additional reactor modules performing N‐alkylation and arylation, deprotection, and amidation to install broad molecular diversity in short order. Continuous flow synthesis enables the safe handling of diazoalkanes at elevated temperatures, and the use of aryl alkyne dipolarphiles under catalyst‐free conditions. This assembly‐line synthesis provides a flexible approach for the synthesis of agrochemicals and pharmaceuticals, as demonstrated by a four‐step, telescoped synthesis of measles therapeutic, AS‐136A, in a total residence time of 31.7 min (1.76 g h⁻¹). Keywords: active pharmaceutical ingredients; agrochemicals; assembly line synthesis; multi-step continuous flow synthesis; pyrazoles
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1002/anie.201704529
