883223-09-4

Upstream product

• 883223-08-3 (S)-methyl 3-methyl-2-((4-(4,4,5,5-tetramethyl-2,3,2-dioxaborolan-2-yl)benzyl)amino)butanoate 
• 638-29-9 n-valeryl chloride 
• 76-09-5 2,3-dimethyl-2,3-butane diol 
• 5084-80-0 tri(4-tolyl)boroxine 
• 195062-57-8 p-tolylboronic pinacol ester 
• 138500-85-3 4-bromomethylphenylboronic acid pinacol ester 
• 73183-34-3 bis(pinacol)diborane 
• 4070-48-8 L-Valine methyl ester 
• 6306-52-1 L-valine methylester hydrochloride 
• 1189547-11-2 methyl N-pentanoyl-L-valinate 

Downstream Products

• 137863-17-3 methyl N-((2’-(1H-tetrazol-5-yl)-[1,1’-biphenyl]-4-yl)methyl)-N-pentanoyl-L-valinate 
• 137862-53-4 N-pentanoyl-N-[[2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]-methyl]-(L)-valine 
• 781664-81-1 N-[[2'-(1-triphenylmethyltetrazol-5yl)biphenyl-4-yl]methyl]-N-valeryl-L-valine methyl ester 
• 137863-90-2 methyl 2-(N-((2'-cyanobiphenyl-4-yl)methyl)pentanamido)-3-methylbutanoate 

Relevant academic research and scientific papers

BIARYLMETHYL HETEROCYCLES

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are biased agonists, or β-Arrestin agonists of the angiotensin II receptor, which may be used as medicaments.

Polymer-supported electron-rich oxime palladacycle as an efficient heterogeneous catalyst for the Suzuki coupling reaction

Various electron-rich oxime palladacycle resins designed as heterogeneous catalysts were employed for the Suzuki coupling reaction of aryl halides with arylboronic acids. The electron-richness of the oxime ligand was controlled by the substituted alkoxy groups. Evaluation based on the electronic effect of the catalysts revealed that the alkoxy-substituted oxime palladacycle resins showed better catalytic activity than palladated Kaiser oxime resin in the Suzuki coupling reactions and that the catalytic activity of oxime palladacycle resins increased as the electron-richness of oxime ligand increased. The most electron-rich oxime palladacycle resin exhibited an excellent catalytic performance for the synthesis of both biaryl and heterobiaryl compounds, despite its heterogeneous system. As a practical application of the catalyst, a valsartan precursor was synthesized in high yield under mild conditions. The electron-rich oxime resin could also be reused for up to 5 cycles while maintaining good catalytic activity in the Suzuki coupling reaction.

Microwave-mediated synthesis of an arylboronate library

A series of arylboronates has been synthesized from the reaction of 2-(2-, (3-, or (4-(bromomethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 1{1-3} respectively with a range of N-, S-, and O-nucleophiles, using microwave-mediated chemistry. For the synthesis of N- and S-substituted boronates, a supported base, PS-NMM, was employed, and many reactions were complete within 15 min. With O-nucleophiles, a mixture of tetrabutylammonium bromide, potassium carbonate, and sodium hydroxide was employed. The resulting aminomethyl, mercaptomethyl, or alkoxy-/phenoxymethyl-arylboronates were subjected to microwave-mediated Suzuki Miyaura coupling reactions to afford a range of biaryls in moderate to good yields. The X-ray structures of five boronates were determined.

Convenient synthesis of Valsartan via a Suzuki reaction

An efficient synthesis of the angiotensin II inhibitor Valsartan (Diovan) is presented. The formation of the aryl-aryl bond represents the key step of its synthesis, which has been done by a Suzuki coupling of aryl boronate with 2-bromophenyl oxazoline with good yield and purity. This method overcomes many of the drawbacks associated with the previously reported syntheses.

Efficient synthesis of valsartan, a nonpeptide angiotensin II receptor antagonist

A highly efficient and convergent approach to the synthesis of the angiotensin II receptor antagonist valsartan (1), one of the most important agents used in antihypertensive therapy today, is described. Directed ortho-metalation of 4-bromotoluene provides the key boronic acid intermediate 11 which was subjected to palladium-catalyzed Suzuki coupling. This method overcomes many of the drawbacks associated with the previously reported syntheses. The saponification of the methyl ester in valsartan was realized in a convenient and economical manner, which is more suitable for industrial production. Georg Thieme Verlag Stuttgart.

INTERMEDIATE COMPOUNDS FOR THE PREPARATION OF AN ANGIOTENSIN II RECEPTOR ANTAGONIST

It comprises new substituted 4-valinylmethylphenyl boronic acids and their derivatives and also its preparation process. It also comprises a preparation process of Valsartan from such intermediates. The process comprises the reaction of the new 4-valinylmethylphenyl boronic compounds with a (halophenyl)tetrazole compound which proceeds with high yields. The process is particularly advantageous in its practical industrial realization because it avoids the use of azide derivatives and also the use of expensive biphenyl intermediates.