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Preparation method of cinacalcet impurity

A technology of cinacalcet and impurities, applied in the field of compound preparation, to achieve the effect of simple operation method, high purity and reasonable process design

Active Publication Date: 2019-07-23
TLC NANJING PHARMA RANDD CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The synthetic method of cinacalcet impurity provided by the present invention has not been reported yet, in order to cinacalcet clinical, pharmacology, pharmacokinetics, toxicology is carried out comprehensive analysis, research, it is very necessary on the basis of prior art , designed and developed the preparation method of cinacalcet impurity, and provided the reference material for the comprehensive analysis of cinacalcet's clinical, pharmacology, pharmacokinetics and toxicology

Method used

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  • Preparation method of cinacalcet impurity
  • Preparation method of cinacalcet impurity
  • Preparation method of cinacalcet impurity

Examples

Experimental program
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Effect test

Embodiment 1

[0028] Preparation of Compound II: Dissolve 50g of m-trifluoromethylphenylacetic acid in dichloromethane, add 58.28g of thionyl chloride, and react at 60°C for 2 hours. When the reaction is complete, take it with 200mL of tetrahydrofuran for later use. Dissolve 31.63g of (R)-(+)-4-isopropyl-2-oxazolinone in 474mL of tetrahydrofuran, add 5g of sodium hydride, stir at 20°C for 20 minutes, dissolve the prepared acid chloride in 50mL of tetrahydrofuran, Add it dropwise to the reaction solution, stir at room temperature for 1.5 hours, after the reaction is over, add 100mL of water under ice bath, spin off most of the tetrahydrofuran, extract three times with 100mL of ethyl acetate, combine the organic layers, dry with anhydrous sodium sulfate, and filter , spin-dried to obtain 79g of crude product, separated by column chromatography to obtain 72g of yellow oil II, the yield was 93.2%.

[0029]

[0030] Preparation of Compound III: Dissolve 31g of Compound II in 620mL of tetrahyd...

Embodiment 2

[0039] Preparation of Compound II: Dissolve 40 g of m-trifluoromethylphenylacetic acid in dichloromethane, add 93.24 g of thionyl chloride, and react at 60°C for 2 hours. When the reaction is complete, take it with 200 mL of tetrahydrofuran for later use. Dissolve 25.31g of (R)-(+)-4-isopropyl-2-oxazolinone in 430mL of tetrahydrofuran, add 4g of sodium hydride, stir at 20°C for 20 minutes, dissolve the prepared acid chloride in 40mL of tetrahydrofuran, Add it dropwise into the reaction solution, stir at room temperature for 10 hours, after the reaction is over, add 100mL of water under ice bath, spin off most of the tetrahydrofuran, extract three times with 100mL of ethyl acetate, combine the organic layers, dry with anhydrous sodium sulfate, and filter , spin-dried to obtain 56g of crude product, separated by column chromatography to obtain 45g of yellow oil II, and the yield was 72.84%.

[0040]

[0041] Preparation of compound III: Dissolve 40 g of compound II in 800 mL ...

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Abstract

The invention discloses a preparation method of a cinacalcet impurity and belongs to the field of medicine synthesis. A whole technology is reasonable in design, strong in operability and convenient for purification. The method takes m-(trifluoromethyl)phenylacetic acid as a starting raw material to synthesize the cinacalcet impurity through five-step reaction. According to the preparation methoddisclosed by the invention, optimal preparation steps and reaction conditions are screened through an experiment; the purity of the cinacalcet impurity prepared by the preparation method reaches 98.8percent or more and a test sample is provided for researching cinacalcet; the cinacalcet impurity has important research value in clinical pharmacokinetic researches.

Description

technical field [0001] The invention relates to a preparation method of a compound, in particular to a preparation method of cinacalcet impurities. [0002] technical background [0003] Cinacalcet is a calcimimetic agent developed by NPS Pharmaceuticals in the United States. It was approved by the FDA in 2004 for the treatment of secondary hyperparathyroidism in patients with kidney disease and dialysis, and hypercalcemia caused by thyroid cancer. . The drug can bind to the calcium-sensing receptor of the parathyroid gland, reduce the secretion of parathyroid hormone, and then lead to a decrease in the level of serum calcium and calcium phosphate products. [0004] With the progress of the times and the improvement of the level of science and technology, people have a fuller understanding of the importance of scientific evaluation of the quality, safety and efficacy of drugs before they are marketed. Among them, the quality of drugs is closely related to the quality of drug...

Claims

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Application Information

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IPC IPC(8): C07C209/58C07C211/29
CPCC07C51/00C07C209/58C07C231/02C07D263/22C07C57/30C07C233/11C07C211/29
Inventor 丁铜锁肖恒胡永铸刘春徐一鸣
Owner TLC NANJING PHARMA RANDD CO LTD
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