A practical synthesis of the major 3-hydroxy-2-pyrrolidinone metabolite of a potent CDK2/cyclin A inhibitor.
The synthesis of the major metabolite of a potent 3-aminopyrazole CDK2/cyclin A inhibitor is presented. A stereoconservative approach starting from malic acid was employed to construct the hydroxy-substituted pyrrolidinone moiety. In the key step of the synthesis the use of cyanoborohydride immobilized on Amberlyst 26 in trifluoroethanol represented a valid alternative to conventional solution-phase reducing agents.
Nesi
Marcella
M
Department of Chemistry, Oncology Business Unit, Nerviano Medical Sciences, Viale Pasteur 10-20014 Nerviano, MI, Italy. marcella.nesi@nervianoms.com
Borghi
Daniela
D
Brasca
Maria Gabriella
MG
Fiorentini
Francesco
F
Pevarello
Paolo
P
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019925:Cyclin A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
C512291:3-hydroxy-2-pyrrolidinone; D019925:Cyclin A; D047428:Protein Kinase Inhibitors; D011760:Pyrrolidinones; D051357:Cyclin-Dependent Kinase 2