The solid-phase synthesis and use of N-monosubstituted piperazines in chemical library synthesis.
An efficient solid-phase synthesis of mono-N-substituted piperazines is presented. The key transformation involves a selective borane amide bond reduction in the presence of a carbamate resin linkage. This synthetic route takes advantage of the large diverse pool of commercially available carboxylic acids, acid chlorides, and sulfonyl chlorides. The solid-phase approach facilitates parallel processing by eliminating the need for column chromatography after each synthetic step. The N-monosubstituted piperazines were shown to react with polymeric activated tetrafluorophenol (TFP) reagents to generate arrays of amides and sulfonamides in good purity for biological testing.
Combinatorial Chemistry Department, Adolor Corporation, 371 Phoenixville Pike, Malvern, Pennsylvania 19355, USA.
Joseph M
JM
Salvino
Baudouin
B
Gerard
Hai Fen
HF
Ye
Berengere
B
Sauvagnat
Roland E
RE
Dolle