34 results about "Valine methyl ester" patented technology

This invention relates to a new synthetic method of valsartan, includes preparation method of intermediate N - ( 1 - oxygen amyl) - N - [ [ 2' - trityl - tetrazolium - 5 - group) - ( 1, 1' - dibenzyl) - 4 - group] - methyl] - L - valine. 2' - ( N - trityl) tetrazolium - 4 - bromoethyl Biphenyl and valine methyl ester ( or other salt) carry out alkylation reaction, after acidylation, by alkaline hydrolysis and acidification to obtain intermediate N - ( 1 - oxygen amyl) - N - [ [ 2' - trityl - tetrazolium - 5 - group) - ( 1, 1' - dibenzyl) - 4 - group] - methyl] - L - valine, then by protection solution to gain Valsartan. This invention belong to pharmaceutical chemistry and organic chemistry region, possess merits of raw material stabilization, yield higher, valsartan optical purity high, industrialization operating easy and so on.

The present invention provides a method for the preparation of N-(1-oxopentyl)-N-[[2′-(1H-tetra-zol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-L-valine (Valsartan) which comprises; treating N-[[2′-(1-triphenylmethyl-tetra-zol-5-yl)biphenyl-4-yl]methyl]-L-valine methyl ester (X) with oxalic acid or its hydrates in a solvent to produce N-[[2′-(1-triph-enylmethyl-tetrazol-5-yl)biphenyl-4-yl]methy]-L-valine methyl ester oxalate (Xa) and treating the compound (Xa) with a base in a solvent followed by reacting with valeryl chloride in presence of base in a solvent to produce N-[[2′-(1-triphenylmethyl-tetra-zol-5-yl)[1,1′biphenyl]-4-yl]methyl]-N-valeryl-L-valine methyl ester (XI), de-protecting the compound (XI) using anhydrous acidic conditions to produce N-(1-oxopentyl)-N-[[2′-(1-H-tetrazol-5-yl)[1,1′biphenyl]-4-yl]methyl-L-valine methyl ester (V) followed by treating with base in a solvent to produce Valsartan.

The invention relates to a synthetic method for a sartan drug intermediate. The method includes: dissolving N-[(2'-cyanobiphenyl-4-base) methyl]-N-amyl acyl-(L)-valine methyl ester and sodium azide in an organic solvent, reacting under the catalytic action of catalyst, and obtaining the drug intermediate N-[(2'-tetra-nitrogen imidazolyl biphenyl-4-base]-N-amyl acyl-(L)-valine methyl ester. Rare-earth metal organic chloride is applied to the preparation process of the sartan drug intermediate, the fact that tributyl tin chloride can be substituted, better effect is obtained, product yield and quality are improved to some extent, reaction time is short, toxicity does not exist, a new assistant catalyst which is economical and environment-friendly is provided for synthesis of the sartan drug intermediate, and the sartan drug intermediate has quite high application value and economic value.

The invention relates to a pH-responsive polyaspartic acid grafted with hydrophobic amino acids and a preparation method thereof, using polyaspartic acid and L-phenylalanine methyl ester hydrochloride as raw materials, through 1-(3- Dimethylaminopropyl)-3-ethyl carbodiimide coupling reaction and alkali washing, obtain polyaspartic acid-grafting-phenylalanine; use polyaspartic acid-grafting-phenylalanine Amino acid and hydrophobic amino acid hydrochloride are used as raw materials, and the product is obtained through coupling reaction and alkali washing. Hydrophobic amino acid hydrochloride including N ε ‑Benzyloxycarbonyllysine benzyl ester hydrochloride, tryptophan methyl ester hydrochloride, valine methyl ester hydrochloride and isoleucine methyl ester hydrochloride; The amino acid contains a pH-responsive anionic carboxyl group and has good biocompatibility. When the polymer concentration is less than 0.1 mg / mL, the survival rate of smooth muscle cells is above 80%. The operation is simple and the cost is low. It is suitable for the field of biomedical drug carrier materials.

The present invention relates to a process for the preparation of pure Valsartan (I) substantially free from impurities of formulae (Ia), (Ib), and (Ic), which comprises: (i) condensing 2-(4′-bromomethylphenyl)benzonitrile of formula (II) with L-valine methyl ester hydrochloride of formula (V) in the presence of a base in a solvent to produce N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester of formula (VI); (ii) treating the compound VI of step (i) with acid followed by treating with base to produce pure compound VI substantially free from dimeric impurity of formula (Via); (iii) reacting the pure compound of formula (VI) with n-valeryl chloride in the presence of a base to produce pure N-valeryl-N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VII) substantially free from alkene impurity of formula (Vila); (iv) reacting the compound of formula (VII) with trialkyltin chloride and a metal azide in a solvent at a reflux temperature to produce N-(1-oxopentyl)-N-[[2′-(2-tributyltintetrazol-5-yl)-(1,1′-biphenyl)-4-yl]methyl]-(L)-valine methyl ester of formula (VHIb) free from thermal degradation impurity (Villa); (v) hydrolyzing the compound of formula (VHIb) in the presence of alkaline conditions to produce Valsartan (I).