168265-56-3

Upstream product

• 5720-05-8 4-methylphenylboronic acid 
• 15561-72-5 3-benzylbenzo[d][1,2,3]triazin-4(3H)-one 
• 7305-08-0 N,N-dimethyl-carbamic acid 4-tolyl ester 
• 28386-90-5 5-benzyl-1-phenyl-1H-tetrazole 
• 624-31-7 4-tolyl iodide 
• 106-38-7 para-bromotoluene 

Downstream Products

• 114798-26-4 lorsartan 
• 138402-11-6 2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one 
• 137862-53-4 N-pentanoyl-N-[[2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]-methyl]-(L)-valine 
• 145040-37-5 candesartan cilexetil 
• 1307853-85-5 1-{[(cyclohexyloxy)carbonyl]oxy}ethyl 1-({4-[2-(1-benzyl-1H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-2-ethoxy-1H-1,3-benzodiazole-7-carboxylate 
• 1215298-35-3 methyl 2-ethoxy-1-({2′-[1-(phenylmethyl)-1H-tetrazol-5-yl][1,1′-biphenyl]-4-yl}methyl)-1H-benzimidazole-7-carboxylate 
• 1307853-81-1 methyl 2-[({2'-[1-benzyl-1H-tetrazol-5-yl]biphenyl-4-yl}methyl)amino]-3-aminobenzoate 
• 1215298-30-8 methyl 2-[({2'-[1-benzyl-1H-tetrazol-5-yl]biphenyl-4-yl}methyl)amino]-3-nitrobenzoate 
• 1307853-80-0 methyl 2-(N-tert-butoxycarbonyl-N-{(2'-[1-benzyl-1H-tetrazol-5-yl]biphenyl-4-yl)methyl}amino)-3-nitrobenzoate 
• 207400-81-5 (1-{[2′-(1-benzyl-1H-tetrazol-5-yl)-1,1′-biphenyl-4-yl]methyl}-2-butyl-4-chloro-1H-imidazol-5-yl)methanol 
• 137863-17-3 methyl N-((2’-(1H-tetrazol-5-yl)-[1,1’-biphenyl]-4-yl)methyl)-N-pentanoyl-L-valinate 
• 144689-63-4 olmesartan medoxomil 
• 144690-92-6 trityl olmesartan medoxomil 
• 936114-12-4 potassium 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl]biphenyl-4-yl]methyl]imidazole-5-carboxylate 

Relevant academic research and scientific papers

Pd(ii)-catalyzed, controllable C-H mono-/diarylation of aryl tetrazoles: Concise synthesis of Losartan

A palladium(ii)-catalyzed C-H arylation directed by tetrazole, a metabolically stable surrogate for the carboxylic acid group in drug design, has been developed. Excellent mono-/di-selectivity was achieved through adjustment of the protecting site on the tetrazole ring. The synthetic utility of this new transformation was demonstrated in the concise total synthesis of Losartan. This journal is

Nickel-Catalyzed Denitrogenative ortho-Arylation of Benzotriazinones with Organic Boronic Acids: an Efficient Route to Losartan and Irbesartan Drug Molecules

Denitrogenative ortho-arylation, vinylation and methylation of 1,2,3-benzotriazin-4-(3H)-ones with organic boronic acids catalyzed by nickel complexes to give a wide range of o-substituted benzamides were demonstrated. Further, the catalytic reaction is successfully applied to the synthesis of the popular hypertensive drugs losartan and irbesartan in high yields. (Figure presented.).

DEPROTECTION METHOD FOR TETRAZOLE COMPOUND

The present invention relates to a method of deprotecting a tetrazole compound, useful as an intermediate for angiotensin II receptor blockers, and provides a novel production method of angiotensin II receptor blockers. Provided is a production method of a compound represented by the formula [3] or [4] or a salt thereof, including (i) reducing a compound represented by the formula [1] or [2] or a salt thereof in the presence of a metal catalyst and an alkaline earth metal salt, or (ii) reacting the compound with a particular amount of Br?nsted acid: wherein each symbol is as defined in the present specification.

Cobalt-catalyzed C-H arylations with weakly-coordinating amides and tetrazoles: Expedient route to angiotensin-ii-receptor blockers

Cobalt-catalyzed C-H arylations enabled the synthesis of biaryl tetrazoles, which are key structural motifs in antihypertensive angiotensin-II-receptor blockers. Thus, weakly-coordinating benzamides were employed for step-economical C-H arylations with ample scope. Further, a low-valent NHC complex enabled first cobalt-catalyzed C-H functionalization by tetrazole assistance.

Carboxylate-assisted ruthenium(II)-catalyzed C-H arylations of 5-aryl tetrazoles: Step-economical access to Valsartan

Carboxylate assistance was key to success for highly efficient ruthenium-catalyzed direct ortho-arylations of tetrazolyl-substituted arenes with aryl halides and triflates in the absence of phosphine ligands. Thus, ruthenium(II) biscarboxylates allowed for C-H bond functionalizations with excellent chemo- and site-selectivities, which set the stage for an atom- and step-economical access to key angiotensin-II-receptor blockers. Mechanistic studies revealed the C-H bond metalation to be reversible, and were suggestive of a rate-determining reductive elimination.