Combinatorial solution-phase synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides.
Solution-phase combinatorial synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides was studied. First, di-tert-butyl (2S,4S)-4-amino-5-oxopyrrolidine-1,2-dicarboxylate hydrochloride was prepared as the key intermediate in five steps from (S)-pyroglutamic acid. Acylation of the amino group followed by acidolytic deprotection gave (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxylic acids, which were then coupled with amines to furnish a library of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides. Four coupling reagents, BPC, EEDQ, TBTU, and PFTU, were tested for the amidation reactions in the final step. Amidations with EEDQ and TBTU led to the desired carboxamides. On the other hand, BPC and PFTU were not suited, since diketopiperazines were sometimes obtained instead of the desired carboxamides.
Malavasic
Crt
C
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, P.O. Box 537, 1000 Ljubljana, Slovenia.
Brulc
Blaz
B
Cebasek
Petra
P
Dahmann
Georg
G
Heine
Niklas
N
Bevk
David
D
Groselj
Uros
U
Meden
Anton
A
Stanovnik
Branko
B
Svete
Jurij
J
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D009682:Magnetic Resonance Spectroscopy; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
D000577:Amides; D011761:Pyrrolidonecarboxylic Acid