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.

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Process Research and Large-Scale Synthesis of 4",6"-Bis((2fluorophenyl)carbamoyl)hecogenyl β-O-Cellobioside:A Potent Cholesterol Absorption Inhibitor.-A facile five step synthesis of the title compound (I), which allowed the preparation of 80 kg of high-purity material in good overall yield, is given. -(URBAN, F. J.; BREITENBACH, R.; BUZON, R. A.; DANIELS, P. J.; DUNN, P. J.; GUT, S.; LEHNER, R. S.; ORRILL, S. L.; WATSON, H. A. JUN.; Org. Process Res. Dev. 2 (1998) 2, 66-70; Process Res. Dev., Cent. Res. Div., Pfizer Inc., Groton, CT 06340, USA; EN)