Design and synthesis of a diverse morpholine template library.
Efficient and general procedures have been developed for the solution-phase preparation of substituted morpholine derivatives, and a library has been produced around generic structure 1. This library was designed with proprietary modeling software for use as a general screening library. The 30 R1 reagents were phenols, and the 275 R2 reagents were taken from five different reagent classes, giving a variety of product classes in the final library of 8250 potential products. All of the library members were generated from a common intermediate, mesylate (5), which was synthesized efficiently, in bulk, in three steps from N-benzylethanolamine (2). High-throughput chemistry using robotics was carried out to produce the 7907 library members, which were individually characterized by reversed-phase LC/MS analysis.
Lainton
Julia A H
JA
Tripos Receptor Research Ltd, Bude-Stratton Business Park, Bude, Cornwall EX23 8LY, United Kingdom.
Allen
Mark C
MC
Burton
Matthew
M
Cameron
Stuart
S
Edwards
Timothy R G
TR
Harden
Grahame
G
Hogg
Rebecca
R
Leung
Wilson
W
Miller
Steven
S
Morrish
Joseph J
JJ
Rooke
Stuart M
SM
Wendt
Bernd
B
D000447:Aldehydes / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015195:Drug Design; D008401:Gas Chromatography-Mass Spectrometry; D017953:Isocyanates / Q000737:chemistry; D017879:Isothiocyanates / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry; D010636:Phenols / Q000737:chemistry; D013441:Sulfinic Acids / Q000737:chemistry
D000447:Aldehydes; D002264:Carboxylic Acids; D017953:Isocyanates; D017879:Isothiocyanates; D009025:Morpholines; D010636:Phenols; D013441:Sulfinic Acids; C044255:sulfonyl chloride