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 discloses a novel method for preparing valsartan, which comprises the steps: taking L-valine methyl ester or L-valine methyl ester hydrochloride and p-bromobenzaldehyde as raw materials, carrying out reductive amination and acidylation reaction to obtain an intermediate, and performing SUZUKI reaction on the intermediate so as to obtain the valsartan. The method is safely operated, and avoids a step of tetrazole synthesis, and azide and other explosible hazardous compounds are not necessarily used; and the used raw materials can be easily obtained, and most of the raw materials are conventional chemical raw materials. In the method, biphenyl derivatives are not required for preparing the valsartan, and biphenyl products are obtained mainly through the suzuki reaction.

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.

A preparation method of 2-bromothiophene relates to a method for improving the 2-position substitution selectivity of thiophene and reducing the production amount of 3-bromothiophene, and belongs to the technical field of preparation of fine chemical products such as medicine. It is characterized in that thiophene is converted into 2-bromothiophene in the presence of L-valine methyl ester. It comprises the following steps: adding sodium bromide and L-valine methyl ester and water, adding sulfuric acid, adding thiophene, and adding hydrogen peroxide. The reaction formula is shown in the accompanying drawing. The invention has the advantages of high thiophene 2-position substitution selectivity, less 3-bromothiophene generation, environmental friendliness and low cost.

The present invention relates to a kind of synthetic method of valsartan intermediate, comprises the following steps: (1) first dissolving following formula II compound in organic solvent, adding acid-binding agent, sodium chloride or potassium chloride and water, stirring evenly , after adding n-valeryl chloride dropwise, carry out insulation reaction; (2) add water to quench after completion of the reaction, carry out alkali washing, pickling, and alkali washing successively, and finally obtain the following formula I compound of the target product by distillation under reduced pressure, i.e. N-[( 2'-cyanobiphenyl-4-yl)methyl]-N-(1-oxopentyl)-L-valine methyl ester. In the present invention, by adding an appropriate amount of sodium chloride or potassium chloride to the reaction system, the occurrence of the hydrolysis reaction of n-valeryl chloride is suppressed by using the same ion effect, thereby reducing the amount of n-valeryl chloride, which is beneficial to improving the purity and yield of the product , reduces production cost, reduces environmental pollution, and is more suitable for industrial production.

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).