A novel synthesis of olmesartan medoxomil and examination of its related impurities / 药学学报
Acta Pharmaceutica Sinica
;
(12): 537-543, 2006.
Article
in Chinese
| WPRIM
| ID: wpr-271411
ABSTRACT
<p><b>AIM</b>To develop a new synthetic route for olmesartan medoxomil.</p><p><b>METHODS</b>Olmesartan medoxomil was prepared from ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate via hydrolysis and lactonization to afford 4,4- dimethyl-2-propyl-4,6-dihydrofuro [3,4-d]-1H-imidazole-6-one which was condensed with 2-(triphenylmethyl)-5-[4'-(bromomethylbiphenyl)-2-yl] tetrazole, followed by esterification with 4-chloromethyl-5-methyl-1,3-dioxol-2-one, and deprotection. The chemical structure of the major impurity in condensation reaction is the regio-isomer in the imidazole moiety, and confirmed by single crystal X-ray diffraction. The corresponding regio-isomer of olmesartan medoxomil was synthesized from the impurity by similar method. Optimization of the condensation conditions reduced the impurity to a negligible quantity.</p><p><b>RESULTS</b>Synthesis of olmesartan medoxomil by the new route gave a product of 60% yield and above 99.0% purity. The content of olmesartan medoxomil regio-isomer was effectively controlled to less than 0.1%.</p><p><b>CONCLUSION</b>A novel synthetic route for olmesartan medoxomil was developed successfully. The olmesartan medoxomil regio-isomer is reported for the first time.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Stereoisomerism
/
Tetrazoles
/
Blood Pressure
/
Molecular Structure
/
Chemistry
/
Angiotensin II Type 1 Receptor Blockers
/
Olmesartan Medoxomil
/
Imidazoles
/
Antihypertensive Agents
Limits:
Animals
Language:
Chinese
Journal:
Acta Pharmaceutica Sinica
Year:
2006
Type:
Article
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