185954-27-2Relevant academic research and scientific papers
SAR of a series of 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3- α]pyridines as potent inhibitors of human eosinophil phosphodiesterase
Duplantier, Allen J.,Bachert, Elizabeth L.,Cheng, John B.,Cohan, Victoria L.,Jenkinson, Teresa H.,Kraus, Kenneth G.,McKechney, Michael W.,Pillar, Joann D.,Watson, John W.
, p. 344 - 349 (2007)
The potency and physical properties of a previously reported 7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]-pyridine series of human eosinophil phosphodiesterase inhibitors were improved by tying the lactam moiety into a triazolo ring. The resulting 5,6-dihy
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
Urban, Frank J.,Anderson, Bruce G.,Orrill, Susan L.,Daniels, Peter J.
, p. 575 - 580 (2013/09/07)
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.
Process for preparing 8-cyclopentyl-6-ethyl-3-[substituted]-5,8-dihydro-4h-1,2,3a,7,8-pentaaza-as-indacenes and intermediates useful therein
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, (2008/06/13)
The invention concerns a method of preparing an 8-cyclopentyl-6-ethyl-3-[substituted]-5,8-dihydro-4H-1,2,3a,7,8-pentaaza-as-indacene compound of Formula (1.0.0): and pharmaceutically acceptable salt forms thereof, where R1 is hydrogen; alkyl; alkoxy; alkoxyalkyl; alkenyl; cycloalkyl, cycloalkylalkyl; a saturated or unsaturated heterocyclic-(CH2)n— group; or a group of Formula (1.1.0): wherein all of said substituents are defined in more detail in the instant specification; comprising (a) subjecting a solventless reaction mixture of γ-caprolactone and p-methoxybenzylamine to heating whereby there is produced an amide compound N-protected by p-methoxybenzyl, of Formula (2.0.0): (b) reducing said amide compound of Formula (2.0.0) whereby there is produced an amino alcohol compound N-protected by p-methoxybenzyl, of Formula (3.0.0): (c) acylating said aminoalcohol compound of Formula (3.0.0) with ethyl oxalyl chloride whereby there is produced an oxalamic acid ethyl ester compound N-protected by p-methoxybenzyl, of Formula (4.0.0): (f) oxidizing said oxalamic acid ethyl ester compound of Formula (4.0.0) whereby there is produced an oxalamide ketone compound N-protected by p-methoxybenzyl, of Formula (5.0.0): (e) ring closing said oxalamide ketone compound of Formula (5.0.0) whereby there is produced a pyridinone compound N-protected by p-methoxybenzyl, of Formula (6.0.0): (f) O-methylating said pyridinone compound of Formula (6.0.0) whereby there is produced a 3-methoxy-pyridinone compound N-protected by p-methoxybenzyl, of Formula (7.0.0): (g) treating said 3-methoxy-pyridinone compound of Formula (7.0.0) with cyclopentylhydrazine, whereby there is produced a pyrazolopyridinone compound N-protected by p-methoxybenzyl, of Formula (8.0.0) (h) deprotecting said pyrazolopyridinone compound of Formula (8.0.0) by removing said p-methoxybenzyl group therefrom, whereby there is produced a lactam compound of Formula (9.0.0): (i) esterifying said lactam compound of Formula (9.0.0) whereby there is produced a corresponding imino ester (imidate) compound of Formula (10.0.0): (j) treating said imino ester (imidate) compound of Formula (10.0.0) with a carboxylic hydrazide compound of Formula (11.0.0): where R1 has the same meaning as set out further above; whereby there is produced said 8-cyclopentyl-6-ethyl-3-[substituted]-5,8-dihydro-4H-1,2,3a,7,8-pentaaza-as-indacene compound of Formula (1.0.0).
