8--6--3--58--4-12378--- PROCESS FOR PREPARING 8-CYCLOPENTYL-6-ETHYL-3-SUBSTITUTED-58-DIHYDRO-4H-123A78-PENTAAZA-AS-INDACENES AND INTERMEDIATES USEFUL THEREIN

摘要

The present invention;(a) heating a solvent-free reaction mixture of γ-caprolactone and p-methoxybenzylamine to obtain an amide compound of formula (2) N-protected by p-methoxybenzyl;;(b) reducing the obtained amide compound of formula 2 to yield an amino alcohol compound of formula 3 N-protected by p-methoxybenzyl;;(c) acylating the obtained amino alcohol compound of formula (3) with ethyl oxalyl chloride to obtain an oxamic acid ethyl ester compound of formula (4) N-protected by p-methoxybenzyl;;(d) oxidizing the obtained oxamic acid ethyl ester compound of formula 4 to obtain an oxalamide ketone compound of formula 5, which is N-protected by p-methoxybenzyl;;(e) closing the obtained oxalamide ketone compound of formula (5) to obtain a pyridinone compound of formula (6) N-protected by p-methoxybenzyl;;(f) O-methylating the obtained pyridinone compound of formula (6) to obtain a 3-methoxy-pyridinone compound of formula (7) N-protected by p-methoxybenzyl;;(g) treating the obtained 3-methoxy-pyridinone compound of formula (7) with cyclopentylhydrazine to obtain a pyrazolopyridinone compound of formula (8) N-protected by p-methoxybenzyl;;(h) deprotecting the obtained pyrazolopyridinone compound of formula 8 by removing p-methoxybenzyl group therefrom to obtain a lactam compound of formula 9;;(i) esterifying the obtained lactam compound of formula (9) to obtain the corresponding imino ester (imidate) compound of formula (10); And;(j) treating the obtained imino ester (imide) compound of formula 10 with a carboxylic acid hydrazide compound of formula 11 to yield 8-cyclopentyl-6-ethyl-3- [substituted] Obtaining a -5,8-dihydro-4H-1,2,3a, 7,8-pentaza-asymmetric-indacene compound;8-cyclopentyl-6-ethyl-3- [substituted] -5,8-dihydro-4H-1,2,3a, 7,8-pentaza-asymmetric-indacene of formula 1 It relates to a process for the preparation of a compound and its pharmaceutically acceptable salts:;In the above formulas,;R ¹ is hydrogen, alkyl, alkoxy, alkoxyalkyl, alkenyl, cycloalkyl, cycloalkylalkyl, saturated or unsaturated heterocyclic- (CH ₂ ) _n -group, or a group of formula;[Wherein,;All substituents are as described in detail herein].