Use of cyclohexylisocyanide and methyl 2-isocyanoacetate as convertible isocyanides for microwave-assisted fluorous synthesis of 1,4-benzodiazepine-2,5-dione library.
A new protocol in which cyclohexylisocyanide and methyl 2-isocyanoacetate are used as convertible isocyanides for Ugi/de-Boc/cyclization/Suzuki synthesis of biaryl-substituted 1,4-benzodiazepine-2,5-diones has been developed. Ugi reactions of Boc-protected anthranilic acids, fluorous benzaldehydes, amines, and cyclohexylisocyanide or methyl 2-isocyanoacetate were carried out at room temperature. Microwave-promoted de-Boc/cyclization reactions afforded 1,4-benzodiazepine-2,5-diones (BZDs). Suzuki coupling reactions further derivatized the BZD ring by removing the fluorous tag and introducing the biaryl group. A thirty three-member biaryl-substituted BZD library containing four points of diversity was prepared by microwave-assisted solution-phase fluorous parallel synthesis.
Zhou
Hongyu
H
St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Zhang
Wei
W
Yan
Bing
B
D001570:Benzodiazepinones / Q000138:chemical synthesis*; D003486:Cyanides / Q000737:chemistry*; D003500:Cyclization; D005461:Fluorine / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D017953:Isocyanates / Q000737:chemistry*; D008872:Microwaves; D015394:Molecular Structure
D001570:Benzodiazepinones; D003486:Cyanides; D017953:Isocyanates; D005461:Fluorine