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

Autor:	Susan L. Orrill, Frank J. Urban, Peter J. Daniels, Bruce G. Anderson
Přispěvatelé:	Inorganic Materials & Catalysis
Rok vydání:	2001
Předmět:	Diketone Organic Chemistry Triazole Pyrazole Combinatorial chemistry chemistry.chemical_compound Dimethyl sulfate chemistry Pyridine Lactam Moiety Dimethylformamide Organic chemistry Physical and Theoretical Chemistry
Zdroj:	Organic Process Research & Development, 5(6), 575-580. American Chemical Society
ISSN:	1520-586X 1083-6160
DOI:	10.1021/op010222x
Popis:	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 commercially available γ-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 dimethyl sulfate and cesium carbonate in dimethylformamide, 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.
Databáze:	OpenAIRE
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