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A New Flow Methodology for the Expedient Synthesis of Drug‐Like 3‐Aminoindolizines
Author(s) -
Lange Paul P.,
Bogdan Andrew R.,
James Keith
Publication year - 2012
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201200316
Subject(s) - chemistry , sonogashira coupling , combinatorial chemistry , tandem , cycloisomerization , flow chemistry , yield (engineering) , continuous flow , catalysis , nanotechnology , organic chemistry , biochemical engineering , palladium , materials science , engineering , metallurgy , composite material
A flow‐based synthesis of diversely functionalized indolizines and their aza‐analogues is described. These drug‐like heterocycles were generated via a tandem Sonogashira/cycloisomerization sequence, starting from widely available 2‐bromopyridines and alkynes, employing a simple catalyst system together with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) as base. The use of flow technology allows a straightforward and rapid access to a variety of novel compounds, and enables linear scale‐up from milligram‐ to gram‐scales without a decrease in yield.