Bixalomer intermediate

A technology of pisalom and intermediates, which is applied in the field of amine phosphate binding agent pisalom intermediates and their preparation, can solve the problems of difficult complete reaction, danger, low yield and the like, and achieves simple reaction operation, three wastes and the like. The effect of less and higher yield

Active Publication Date: 2015-12-02
NANJING HUAWE MEDICINE TECH DEV
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This synthesis method has a short route, but it needs to use Raney-Co to catalyze the hydrogenation, and the Raney-Co is very active, which makes the operation dangerous. At the same time, it is difficult to complete the hydrogenation reaction under this condition. The disadvantages such as low efficiency, its reaction equation is as follows:

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
  • Bixalomer intermediate
  • Bixalomer intermediate
  • Bixalomer intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1: Synthesis of 3,3'-dibenzyloxyamide dipropylamine (compound III)

[0029] Add 4g of 3,3'-diaminodipropylamine, 9.3g of triethylamine and 30mL of dichloromethane into a 100mL reaction flask, control the temperature at 0-10°C, mix 15.5g of benzyl chloroformate and 20mL of dichloromethane Afterwards, it was added dropwise into the reaction flask, and the reaction was monitored by TLC to be complete. Pour the reaction solution into a beaker, stir and wash with 3*200mL saturated aqueous sodium carbonate solution, then wash with 200mL saturated brine, separate the layers, dry with anhydrous sodium sulfate, filter and spin off the solvent to obtain 11.46g3,3' -dibenzyloxyamide dipropylamine, the productive rate is 97.1%, and the HPLC detection purity is 94.2%. 2 g was purified by column chromatography to obtain 1.4 g of pure product.

[0030] MS(ESI+,m / z)(M+H) + = 400.26.

[0031] 13 C-NMR (300MHz, CDCl 3 ):δ=28.2(-CH 2 CH 2 CH 2 -),39.2(-CONHCH 2 -),46.6(-...

Embodiment 2

[0033] Example 2: Synthesis of 3,3'-dibenzyloxyamide dipropylamine (compound III)

[0034] Add 4g of 3,3'-diaminodipropylamine, 9.3g of triethylamine and 30mL of dichloromethane into a 100mL reaction flask, control the temperature at 0-10°C, mix 10.3g of benzyl chloroformate and 20mL of dichloromethane Afterwards, it was added dropwise into the reaction flask, and the reaction was monitored by TLC to be complete. Pour the reaction liquid into a beaker, stir and wash with 3*200mL saturated aqueous sodium carbonate solution, then wash with 200mL saturated brine, separate the layers, dry with anhydrous sodium sulfate, filter and spin off the solvent to obtain 10.9g3,3' -dibenzyloxyamide dipropylamine, the productive rate is 89.5%, and the HPLC detection purity is 98.9%.

[0035] MS(ESI+,m / z)(M+H) + = 400.26.

Embodiment 3

[0036] Example 3: Synthesis of 3,3'-dibenzyloxyamide dipropylamine (compound III)

[0037] Add 4g of 3,3'-diaminodipropylamine, 9.3g of triethylamine and 30mL of dichloromethane into a 100mL reaction flask, control the temperature at 0-10°C, mix 13.0g of benzyl chloroformate and 20mL of dichloromethane Afterwards, it was added dropwise into the reaction flask, and the reaction was monitored by TLC to be complete. Pour the reaction solution into a beaker, stir and wash with 3*200mL saturated aqueous sodium carbonate solution, then wash with 200mL saturated brine, separate the layers, dry with anhydrous sodium sulfate, filter and spin off the solvent to obtain 11.6g3,3' -dibenzyloxyamide dipropylamine, the yield is 95.3%, and the HPLC detection purity is 97.6%.

[0038] MS(ESI+,m / z)(M+H) + = 400.26.

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 particularly relates to an amine phosphate binder bixalomer intermediate and a preparation method thereof. The preparation method comprises the following steps: reacting a raw material 3,3'-diamidodipropyl amine under the action of benzyl chloroformate to obtain 3,3'-dibenzyloxyamidodipropyl amine, carrying out substitution reaction on the 3,3'-dibenzyloxyamidodipropyl amine and 1,4-dibromobutane or 1,4-dichlorobutane to obtain N,N,N',N'-tetra(3-dibenzyloxyamido)-1,4-butanediamine, and carrying out deprotection by pressure hydrogenation under the action of Pd-C to obtain N,N,N',N'-tetra(3-aminopropyl)-1,4-butanediamine. The method has the advantages of cheap and accessible raw materials, operable reaction, high yield and fewer three wastes, and thus, has excellent industrial prospects.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to an amine phosphate binding agent pisalom intermediate and a preparation method thereof. Background technique [0002] Bixalomer is a drug for the treatment of hyperphosphatemia caused by chronic kidney disease dialysis. It was applied for marketing in Japan by Astellas Pharma in June 2012, and its trade name is Kiklin. Bisalom is an amine phosphate binder that is not absorbed after oral administration and inhibits phosphate absorption by reducing the serum phosphorus concentration in the gastrointestinal tract. [0003] E.M.M.deBrabander-vandenBerg et al. used 1,4-butanediamine and acrylonitrile as raw materials to obtain tetracyanopropyl-1,4-butanediamine through addition reaction, and then used Raney-Co for pressurized catalysis Reduction gives tetraaminopropyl-1,4-butanediamine. This synthesis method has a short route, but it needs to use Raney-Co to catalyze t...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07C211/14C07C209/62C07C271/20C07C269/04
Inventor 包金远徐峰蒋玉伟张孝清赵冬冬
Owner NANJING HUAWE MEDICINE TECH DEV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap