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PROCESS FOR THE SYNTHESIS OF PURE (N-(1-OXOPENTYL)-N-[[2′-(1H-TETRAZOL-5-YL)[1,1′-BIPHENYL]-4-YL]-METHYL]-L-VALINE)

IP.com Disclosure Number: IPCOM000198976D
Publication Date: 2010-Aug-19
Document File: 2 page(s) / 116K

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The IP.com Prior Art Database

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PROCESS FOR THE SYNTHESIS OF PURE (N-(1-OXOPENTYL)-N-[[2′-(1H- TETRAZOL-5-YL)[1,1′-BIPHENYL]-4-YL]-METHYL]-L-VALINE)

(N-(1-oxopentyl)-N-[[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]-methyl]-L-valine) of formula I, is an orally active specific A-II receptor antagonist used as a hypotensive drug. A-II receptor antagonists are safe and effective agents for the treatment of hypertension, anxiety, glaucoma, and heart failure, either alone or in conjunction with hydrochlorothiazide.

O OH

N

Provided is an improved process for preparation of pure (N-(1-oxopentyl)-N-[[2′-(1H- tetrazol-5-yl)[1,1′-biphenyl]-4-yl]-methyl]-L-valine).

The process comprises: reacting 4-bromomethyl-2'-(l-triphenylmethyltetrazol-5- yl)biphenyl (MBB-Br) with L-valine methyl ester in a polar aprotic solvent such as dichloromethane, dichloroethane, N,N- dimethylformamide (DMF), Tetrahydrfuran (THF), and a base such as triethylamine, pyridine, DIPEA (N,N-Di isopropylethylamine), alkali and alkaline earth metal carbonates or bicarbonates or hydroxides, to produce N- [[2'-(l-triphenylmethyltetrazol-5-yl)biphenyl-4-yl]- methyl] -L-valine methyl ester (V3' base), without isolating, treating N-[[2'-(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4- yl]methy]-L-valine methyl ester (V3' base) with a base such as triethylamine, pyridine, DIPEA (N,N-Di isopropylethylamine), alkali and alkaline earth metal carbonates or bicarbonates or hydroxides, preferably DIPEA in a polar aprotic solvent such as dichlo...