Seki M * Mitsubishi Tanabe Pharma Corporation, Osaka, Japan
An Efficient C–H Arylation of a 5-Phenyl-1
H-tetrazole Derivative: A Practical Synthesis of an Angiotensin II Receptor Blocker.
Synthesis 2012;
44: 3231-3237
Key words
candesartan cilexetil - angiotensin II receptor antagonists - C–H arylation - ruthenium
- transfer hydrogenation
Significance
Candesartan cilexetil (Atacand®) is an angiotensin II receptor antagonist that is prescribed for the treatment of
hypertension. It is a prodrug that is hydrolyzed to candesartan in the gut. The synthesis
depicted, features an efficient protocol for ruthenium-catalyzed C–H arylation of
the tetrazole A.
Comment
A significant challenge in this small-scale synthesis was the final removal of the
benzyl protecting group from the tetrazole unit using transfer hydrogenation. Best
results were obtained using a ‘thickshell’ Pd/C catalyst from Evonik.
