C. Ramesh, R. B. Reddy, G. M. Reddy
2006
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Journal
Heterocyclic Communications
Abstract
An improved process for the preparation of 7V-(2,3-dihydrobenzo[l,4]dioxin-2carbonyl)piperazine 2 and its hydrochloride from ethyl-2,3-dihydro-l,4-benzodioxin-2-carboxylate 3 and piperazine in a single step has been described. The compound 2 is an important intermediate in the preparation of anti-hypertensive agent, Doxazosin. 7V-Acylalkylenediamines are used to react with 4-amino-2-chloro-6,7-dimethoxy quinazolines 4 to give a variety of anti-hypertensive agents. For example Doxazosin mesylate 1 is an anti-hypertensive drug contains N-acylalkylenediamine moiety. Doxazosin mesylate 1 is indicated for the treatment of the urinary outflow obstruction and obstructive and irrigative symptoms associated with benign prostate hyperplasia (BPH), obstructive symptoms (hesitation, intermittency, dribbling, weak urinary stream, incomplete emptying of the bladder) and irritative symptoms (nocturia, daytime frequency, urgency, burning). Doxazosin mesylate 1 is also indicated for the treatment of hypertension. It shows a great structural similarity to the older representatives of this class, Prazosin hydrochloride and Terazosin hydrochloride, whereas the two latter active substances are used primarily in the treatment of high blood pressure. In the case of compound 1, there is an additional indication, namely, the treatment of BPH. Unlike Prazosin and Terazosin, 1 is used therapeutically not as hydrochloride but as the mesylate, that is, as a salt of methane sulfonic acid. The synthesis leads to an improved process for the preparation of 7V-(2,3-dihydro-l,4-benzodioxin-2-ylcarbonyl)piperazine 2 and its hydrochloride from ethyl-2,3-dihydro-l,4-benzodioxin-2-carboxylate 3 in a single step. The yields are comparatively higher and consistent. The compound N-(2,3-dihydro-1.4benzodioxin-2-yl carbonyl) piperazine 2 is an important intermediate in the preparation of antihypertensive agent, Doxazosin. Introduction