- New approaches to endothelin receptor antagonist-bosentan
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An improved and efficient synthetic process developed for an endothelin receptor antagonist, bosentan monohydrate by condensing a key intermediate 4-tert-butyl-N-(6-hydroxy-5-(2-methoxyphenoxy)-2,2'-bipyrimidine-4-yl) benezenesulfonamide 5 with commercially cheaper chloro acetonitrile and α-halo esters. This synthetic approach efficiently provides highly pure bosentan without formation of the major impurity 2 (dimer) and less than 0.15% of Nalkylated impurity 3 and pyrimidinone impurity 5 in the final product. In the present process upon purification of bosentan monohydrate gave overall yield of 62-65%.
- Rebelli, Pradeep,Yerrabelly, Jayaprakash Rao,Yalamanchili, Bharathi Kumari,Kommera, Rajashekar,Ghojala, Venkat Reddy,Bairy, Kondal Reddy
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p. 364 - 368
(2013/07/26)
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- PROCESS FOR THE PREPARATION OF BOSENTAN
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The invention concerns a new process for the preparation of bosentan or bosentan monohydrate by reaction of compound of Formula II with ethylene glycol in the presence of potassium bases and the potassium salt of bosentan.
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Page/Page column 3
(2012/03/08)
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- IMPROVED PROCESS FOR THE PREPARATION OF 4-(1,1-DIMETHYLETHYL)-N-[6-(2-HYDROXYETHOXY)-5-(2-METHOXYPHENOXY)[2,2'-BIPYRIMIDIN]-4-YL]BENZENESULFONAMIDE
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The present invention relates to improved process for the preparation of 4-(1,1-dimethylethyl)-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy) [2,2'-bipyrimidin]-4-yl] benzene sulfonamide monohydrate. Formula (I)
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- Facile one-pot process for large-scale production of highly pure bosentan monohydrate, an endothelin receptor antagonist
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Described is an efficient, economic, and one-pot process for the production of highly pure bosentan (1), an endothelin receptor antagonist. The synthesis comprises the reaction of 4,6-dichloro-5-(2-methoxyphenoxy)-2,2′- bipyrimidine (2) with 4-tert-butylbenzenesulfonamide (3) and ethylene glycol (4) in acetonitrile in the presence of potassium carbonate to yield bosentan (1) in the same pot. The present work also describes a novel purification method for the removal of critical dimer impurity (7) and 6-hydroxy impurity (8) in 1 by preparation of bosentan ammonium salt (6) using inexpensive ammonium hydroxide. Upon purification, bosentan monohydrate (1) with an overall yield of 68% and HPLC purity of 99.90% was achieved.
- Niphade, Navnath C.,Jagtap, Kunal M.,Gaikawad, Chandrashekhar T.,Jachak, Madhukar N.,Mathad, Vijayavitthal T.
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p. 1382 - 1387
(2012/01/11)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF BOSENTAN
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The present application provides purification of Bosentan crude by making its crystalline potassium salt, which is further converted to Bosentan (I) with bis-sulfonamide (VIII) and deshydroxyethyl (IX) impurities to less than 0.2% by HPLC analysis.
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Page/Page column 21
(2011/04/14)
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- PROCESS FOR THE PREPARATION OF BOSENTAN
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The invention concerns a new process for the preparation of bosentan or bosentan monohydrate and a new salt of bosentan.
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Page/Page column 8; 9
(2010/10/03)
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- PROCESS FOR THE PREPARATION OF ENDOTHELIN RECEPTOR ANTAGONISTS
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The present invention relates to a process for the preparation of endothelin receptor antagonists, in particular bosentan, in which a compound of formula (II) reacts with an alkylating agent X-R formula (II), wherein R is either -CH2CH2OH or a group that can be transformed into - CH2CH2OH; X is a leaving group; and R2 is a 4-terf-butylbenzenesulfonamido group or a group that can be transformed into 4-terf-butylbenzenesulfonamido group; and further transforming the resulting product into bosentan. Useful intermediates are disclosed, its use for the preparation of bosentan, as well as pharmaceutical compositions comprising the product obtained by the above process.
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Page/Page column 15
(2010/04/03)
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- PROCESSES FOR THE PREPARATION OF BOSENTAN AND RELATED COMPOUNDS USING NOVEL INTERMEDIATES
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Provided herein are novel, commercially viable and industrially advantageous processes for the preparation of substantially pure ethylene glycol sulfonamide compounds such as bosentan using novel intermediates.
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- IMPROVED AND NOVEL PROCESS FOR THE PREPARATION OF BOSENTAN
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The present invention relates to an improved and novel process for the preparation of bosentan compound of formula (1). The present invention also relates to a crystalline form of bosentan and its intermediates.
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Page/Page column 19; 28
(2009/09/05)
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- PROCESS FOR INTRODUCTION OF HYDROXYETHOXY SIDE CHAIN IN BOSENTAN
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The present invention relates to an improved process for the preparation of bosentan. In particular it relates to a process for preparing bosentan substantially free from the dirner impurity of formula (II) and the 6-hydroxy impurity of formula (III). The invention also relates to a pharmaceutical composition comprising bosentan and its use in the treatment of endothelin-receptor mediated disorders.
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Page/Page column 16
(2009/03/07)
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