I  U  P  A  C

News & Notices

Organizations & People

Standing Committees




. . CI
. . PAC
. . Macro. Symp.

. . Books
. . Solubility Data



Links of Interest

Search the Site

Home Page


Pure Appl. Chem. Vol. 73, No. 9, pp. 1401-1409 (2001)

Pure and Applied Chemistry

Vol. 73, Issue 9


Chemical development of the vasopressin receptor 2 antagonist SR-121463*

István Hermecz,1, Andrea Sánta-Csutor2, Csaba Gönczi2, Gergely Héja2, Éva Csikós2, Kálmán Simon3, Ágota Smelkó-Esek3, and Benjámin Podányi3

1Preclinical Development, 2Synthetic Development, 3Preclinical Analytical Development Laboratories; Chinoin Pharmaceutical and Chemical Works Ltd., H-1045 Budapest, Tó u. 1-5, Hungary

Abstract: A facile convergent total synthesis of the selective, potent, and orally active V2 non-peptide antagonist, SR-121463, was developed by modification of the discovery route. One of the late intermediates, the sulfonyl chloride 1, was synthesized from 3-hydroxybenzoic acid (19) by regioselective sulfonation, O-methylation and amidation in four steps. Another late intermediate, indolin-2-one 2, was prepared from p-phenetidine (8) through the indolin-2-one 16, where the cyclohexanone moiety of 27 was introduced into the active 3-methylene group of 16 by sequential transformation using methyl acrylate and KOtBu. After formation of the cyclic ketal moiety of 13, its ring-opening was achieved by using NaBH4 in the presence of CCl3COOH. The morpholino group in 2 was introduced in accordance with the discovery approach, starting from the 2-hydroxyethoxy derivative 14 through the tosyloxy derivative 15 with morpholine in a one-pot reaction. In this way, the indolin-2-one 2 was synthesized from 8 in six steps. Finally, acylation of the indolin-2-one 2 was achieved with the sulfonyl chloride 1 in the presence of KOtBu in dimethyl sulfoxide (DMSO) at room temperature. This synthetic route proved to be applicable for the large-scale synthesis of SR-121463.

*Plenary lecture presented at the Hungarian-German-Italian-Polish Joint Meeting on Medicinal Chemistry, Budapest, Hungary, 2 –6 September 2001. Other presentations are published in this issue, pp. 1387-1509.

Back to Contents for access to full text


Page last modified 29 November 2001.
Copyright © 2001 International Union of Pure and Applied Chemistry.
Questions or comments about IUPAC, please contact, the Secretariat.
Questions regarding the website, please contact web manager.