Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Method for preparing cinacalcet hydrochloride

A technology of cinacalcet hydrochloride and ethyl acetate, which is applied in the field of drug synthesis, can solve the problems of high price and high production cost, and achieve the effects of less impurities, high economic value and high product yield

Active Publication Date: 2017-06-13
JIANGSU SUZHONG PHARM GRP CO LTD +1
View PDF19 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But the starting material 3-(3-(trifluoromethyl)phenyl) propan-1-amine price of this method is higher; First obtain the racemate and then split, half of the optical isomers are discarded, and the production cost higher

Method used

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
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for preparing cinacalcet hydrochloride
  • Method for preparing cinacalcet hydrochloride
  • Method for preparing cinacalcet hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The preparation method of cinacalcet hydrochloride in the present embodiment comprises the following steps

[0037] (1) Add 450 ml ethyl acetate, 0.20 mol (about 45.0 g) m-bromotrifluoromethylbenzene (II), 0.20 mol (about 4.8 g) magnesium powder, 0.002 mol (about 0.5 g) iodine to a 1000 ml reaction bottle granules, slowly heated to 55°C, kept stirring for 8 hours, stopped heating, slowly cooled to 0-10°C, slowly added 0.20mol (about 18.2g) of acryloyl chloride (Ⅲ) dropwise, and the dropwise addition was completed in 60 minutes.

[0038] After the dropwise addition, stir overnight at 0~10°C, slowly add 180ml of ice-water mixture, stir for 30 minutes, transfer the reaction solution into a 1000ml separatory funnel, discard the incompletely dissolved solids, let the mixture stand for 15 minutes, and separate the liquids. The lower aqueous phase was discarded.

[0039] Add 180ml of purified water into the separatory funnel, oscillate, shake well, let stand for 15 minutes, s...

Embodiment 2

[0051] The preparation method of cinacalcet hydrochloride in the present embodiment comprises the following steps

[0052] (1) Add 450 ml tetrahydrofuran to a 1000ml reaction bottle, add 0.20mol (about 45.0g) m-bromotrifluoromethylbenzene (II), 0.213mol (about 5.1g) magnesium powder, 0.00236mol (about 0.6g) iodine particles , slowly heated to 50~60°C, kept warm and stirred for 8h to generate Grignard's reagent, then stopped heating, slowly cooled to 0~10°C, slowly added 0.212mol (about 19.2g) of acryloyl chloride (Ⅲ) dropwise, and the dropwise addition was completed in 60 minutes .

[0053] After the dropwise addition, stir overnight at 0~10°C. The next day, slowly add 180ml of ice-water mixture, stir for 30 minutes, transfer the reaction solution into a 1000ml separatory funnel, discard the incompletely dissolved solids, let the mixture stand for 15 minutes, separate the liquids, and discard the lower aqueous phase.

[0054] Add 180ml of purified water into the separatory f...

Embodiment 3

[0061] The preparation method of cinacalcet hydrochloride in the present embodiment comprises the following steps

[0062] (1) Add 450 ml of diethyl ether, 0.20 mol (about 45.0 g) of m-bromotrifluoromethylbenzene (II), 0.242 mol (about 5.8 g) of magnesium powder, and 0.00256 mol (about 0.65 g) of iodine particles into a 1000 ml reaction bottle, Slowly heat to 55°C, keep stirring for 8 hours, stop heating, slowly cool down to 0-10°C, slowly add 0.23mol (about 20.9g, 18.8ml) of acryloyl chloride (Ⅲ) dropwise, and dropwise complete in 60 minutes.

[0063] After the dropwise addition, stir overnight at 0~10°C. The next day, slowly add 180ml of ice-water mixture, stir for 30 minutes, transfer the reaction solution into a 1000ml separatory funnel, discard the incompletely dissolved solids, let the mixture stand for 15 minutes, separate the liquids, and discard the lower aqueous phase.

[0064] Add 180ml of purified water into the separatory funnel, oscillate, shake well, let stand ...

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

PUM

No PUM Login to View More

Abstract

The invention discloses a method for preparing cinacalcet hydrochloride and belongs to the field of synthesis and preparation of chemical drugs. The method disclosed by the invention comprises the following steps: taking bromo-alpha,alpha,alpha-trifluorotoluene (II) and acryloyl chloride (III) as raw materials, and preparing m-trifluoromethyl acrylketone (IV) through a coupled reaction; carrying out an addition reaction between (IV) and (R)-1-(1-naphthyl) ethamine (V) so as to generate (R)-3-(1-(1-naphthyl)ethylamino)-1-(3-trifluoromethyl)phenyl)-1-acetone (VI); reducing (VI) to prepare N-((1R)-1-(1-naphthyl)ethyl)-3-(3-trifluoromethyl)phenyl)-1-propylamine (cinacalcet) (VII); carrying out a salt forming reaction on cinacalcet, thereby obtaining N-((1R)-1-(1-naphthyl)ethyl)-3-(3-trifluoromethyl)phenyl)-1-propylamine hydrochloride, namely the cinacalcet hydrochloride (I). According to the route, the cheap and readily available bromo-alpha,alpha,alpha-trifluorotoluene (II) and acryloyl chloride (III) are taken as the raw materials, a few steps are needed, usage of compounds of a heavy metal Pd and metal reducing agents LiAlH4, NaBH4 and the like is avoided, and the method is safe, environmentally friendly and economic and is suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a method for synthesizing cinacalcet hydrochloride. Background technique [0002] Cinacalcet hydrochloride (I), its structural formula is , is a calcimimetic agent developed by NPS Pharmaceuticals of 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. [0003] The synthetic method of cinacalcet hydrochloride mainly contains following three kinds at present: [0004] One is to use 3-(3-(trifluoromethyl)phenyl) propionic acid and its derivatives as starting materials, such as patent documents US2007259964A1, WO2008058235A2, CN102718662A, CN103739500A reported 3-(3-(trifluoromethyl) ) phenyl) propionic acid and its derivatives (mixed acid anhydride, acid halide or alkoxy ester) and (R)-1-(1-naphthyl) ethylamine are condensed to obtain amide a...

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

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07C209/00C07C209/68C07C211/30
CPCC07C45/46C07C209/00C07C209/68C07C221/00C07C211/30C07C225/10C07C49/235
Inventor 唐海涛岳永力何达赵耕先葛海涛王坤姜龙戴德玲
Owner JIANGSU SUZHONG PHARM GRP CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com