Process Research and Large-Scale Synthesis of a Novel 5,6-Dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridine PDE-IV Inhibitor

F.J. Urban, B.G. Anderson, S.L. Orrill, P.J. Daniels

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)

Abstract

An efficient synthesis of the PDE IV inhibitor, 9H-cyclopentyl-7-ethyl-3-(thiophen-2-yl)-pyrazolo[3,4-c]-1,2,4-triazolo-5,6-dihydro-[4,3-a]pyridine 1 is described. Starting from com. available g-caprolactone, the synthesis was carried out in 10 steps. Key transformations were the selective O-methylation of diketone, 3-hydroxy-1-(4-methoxybenzyl)-4-propionyl-5,6-dihydro-1H-pyridin-2-one, with di-Me sulfate and cesium carbonate in DMF, a one-pot pyrazole formation with subsequent acidic deprotection to provide lactam, 1-cyclopentyl-3-ethyl-1,4,5,6-tetrahydropyrazolo[3,4-c]pyridin-7-one, and finally the utilization of imidate, 1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine for the introduction of the triazole moiety. This process avoided the use of harsh reaction conditions, undesirable reagents and overcame the environmental concerns in the original synthesis. [on SciFinder (R)]
Original languageEnglish
Pages (from-to)575-580
JournalOrganic Process Research & Development
Volume5
Issue number6
DOIs
Publication statusPublished - 2001

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