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.
Salvino
Joseph M
JM
Combinatorial Chemistry Department, Adolor Corporation, 371 Phoenixville Pike, Malvern, Pennsylvania 19355, USA.
Gerard
Baudouin
B
Ye
Hai Fen
HF
Sauvagnat
Berengere
B
Dolle
Roland E
RE