Stereoselective synthesis of cis-1,3-disubstituted cyclobutyl kinase inhibitors.
Two synthetic routes to a series of structurally novel kinase inhibitors containing a cis-1,3-disubstituted cyclobutane are described. The first route utilized addition of 3-aminocyclobutanol to 1,4-dinitroimidazole 5 as the crucial step in preparing 1, whereas the second route employed a novel 1,4-addition of 4-nitroimidazole 18 to in situ generated cyclobutenone 17 as the key reaction. This allowed for a stereoselective and shorter synthesis that eliminated the use of potentially explosive 1,4-dinitroimidazole 5. [structure: see text]
Helal
Christopher J
CJ
Neuroscience Medicinal Chemistry, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. chris_j_helal@groton.pfizer.com
Kang
Zhijun
Z
Lucas
John C
JC
Bohall
Brooks R
BR
D002073:Butanes / Q000737:chemistry*; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000737:chemistry; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
D002073:Butanes; D004791:Enzyme Inhibitors; D009593:Nitroimidazoles; C046888:butane; D010770:Phosphotransferases; C052587:4-nitroimidazole