Preparation and purification method of valsartan

A technology for valsartan and valine, which is applied in the field of preparation and purification of valsartan, can solve the problems of difficult control of tin content, difficult operation, long reaction time, etc., and achieves the avoidance of tin metal residue, stable process, The effect of process optimization
CN107056720AInactive Publication Date: 2017-08-18湖南千金湘江药业股份有限公司
23 Cites 7 Cited by

Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
湖南千金湘江药业股份有限公司
Publication Date
2017-08-18
Estimated Expiration
Not applicable · inactive patent

Smart Images

  • Figure 1
    Figure 1
  • Figure 2
    Figure 2
  • Figure 3
    Figure 3
Patent Text Reader

Abstract

The invention relates to the field of medicinal chemistry and discloses a preparation and purification method of valsartan. The method comprises the steps of (S1) adding L-valine and alcohol to a reaction kettle, slowly dropwise adding thionyl chloride, carrying out heating reflux reaction, adding isopropyl acetate for pulping, carrying out suction filtration to obtain an intermediate 1; (S2) carrying out nucleophilic reaction on the intermediate 1 and a starting material 2 in a solvent under an alkaline condition to obtain an intermediate 2; (S3) carrying out nucleophilic reaction on the intermediate 2 and valeryl chloride in the solvent under the alkaline condition to obtain an intermediate 3; and (S4) carrying out cyclization reaction on the intermediate 3, sodium azide and a catalyst ((-)-sparteine-Cu (II) complex) in the solvent, washing, crystallizing and drying to obtain the valsartan. The sodium azide and the catalyst ((-)-sparteine-Cu (II) complex) are used in the cyclization reaction, and the cyclization yield can reach 90%. According to the purification method, the purity of the raw materials of the valsartan is greater than 99.99%, the content of a solvent residue (ethyl acetate) is smaller than 0.5%, the content of a specific impurity is smaller than 0.1%, other unknown individual impurities are avoided and an enantiomer impurity is not detected.
Need to check novelty before this filing date? Find Prior Art

Description

technical field

[0001] The invention relates to the field of medicinal chemistry, more specifically, to a method for preparing and purifying valsartan. Background technique

[0002] Valsartan (valsartan), chemical name N-(1-oxopentyl) N-[4-[2-(1H-tetrazol-5 base) phenyl] benzyl]-L-valine, is the following Another new type of antihypertensive drug after calcium ion channel blockers and angiotensin converting enzyme inhibitors (ACEI), it is an angiotensin II (angiotensin II) AT receptor antagonist, avoiding calcium antagonists and ACEI It has the advantages of significant curative effect and good tolerance.

[0003] There are many synthetic patent reports of existing valsartan, and the methods are different. The main synthetic methods are as follows:

[0004] Among them, US5399578 is the first to report the use of 2'-cyano-4-formyl biphenyl as a raw material, and the p-toluenesulfonate of protected L-valine benzyl ester through reductive amination reaction, n-valerylation R...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More