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Process for producing 8-cyclopentyl-6-ethyl-3- substituted -5,8-dihydro-4H-1,2,3a, 7,8-pentaaza-as-indacene and intermediates useful therefor
Process for producing 8-cyclopentyl-6-ethyl-3- substituted -5,8-dihydro-4H-1,2,3a, 7,8-pentaaza-as-indacene and intermediates useful therefor
The invention concerns a method of preparing an 8-cyclopentyl-6-ethyl-3-ÄsubstitutedÜ-5,8-dihydro-4H-1,2,3a,7,8-pentaa za-as-indacene compound of Formula (1.0.0): CHEM 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): CHEM wherein all of said substituents are defined in more detail in the instant specification; comprising: (a) subjecting a solventless reaction mixture of gamma -caprolactone and p-methoxybenzylamine to heating whereby there is produced an amide compound N-protected by p-methoxybenzyl, of Formula (2.0.0): CHEM (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): CHEM (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): CHEM (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): CHEM (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): CHEM (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): CHEM (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): CHEM (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): CHEM (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): CHEM (j) treating said imino ester (imidate) compound of Formula (10.0.0) with a carboxylic hydrazide compound of Formula (11.0.0): CHEM where R1 has the same meaning as set out further above; whereby there is produced said 8-cyclopentyl-6-ethyl-3-ÄsubstitutedÜ-5,8-dihydro-4H-1,2,3a,7,8-pentaa za-as-indacene compound of Formula (1.0.0).
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