Supercharge Your Innovation With Domain-Expert AI Agents!

Ammonium carboxylate salt compound and crystal forms and amorphous substance thereof and preparation methods of compound, crystal forms and amorphous substance

A technology of compounds and crystal forms, applied in the preparation of organic compounds, the preparation of carboxylic acid amides, the preparation of cyanide reactions, etc., can solve problems such as difficulty in operation

Active Publication Date: 2018-11-13
WUHAN LL SCI & TECH DEV
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The inventor summed up the prior art and found that AHU-377 exists in the form of a thick substance at room temperature. During the industrial production of LCZ696, the transfer and quantification of the raw material of the thick substance AHU-377 have insurmountable operational difficulties

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
  • Ammonium carboxylate salt compound and crystal forms and amorphous substance thereof and preparation methods of compound, crystal forms and amorphous substance
  • Ammonium carboxylate salt compound and crystal forms and amorphous substance thereof and preparation methods of compound, crystal forms and amorphous substance
  • Ammonium carboxylate salt compound and crystal forms and amorphous substance thereof and preparation methods of compound, crystal forms and amorphous substance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0175] Synthesis of embodiment 1 formula (A) compound

[0176] 1.1 Synthesis of (2R,4S)-5-([1,1-biphenyl)-4-amino-2-methylpentanoic acid ethyl ester hydrochloride:

[0177]

[0178] Add (2R,4S)-5-(biphenyl-4-yl)-4-[(tert-butoxycarbonyl)amino]-2-methylpentanoic acid ( 50g, 0.13mol) and absolute ethanol (500ml), stirred and dissolved at room temperature, and thionyl chloride (23.3g, 0.195mol) was added dropwise. After the addition, the temperature was raised to 50-60°C for 3-3.5h. Cool and concentrate to dryness under reduced pressure. The residue was washed with ethyl acetate, and the ethanol residue in the concentrate was monitored by GC to be no more than 15%, then ethyl acetate (500ml) was added, stirred at room temperature, and beaten for 3h; filtered and dried to obtain (2R,4S)-5-([1 , 1-biphenyl)-4-amino-2-methylpentanoic acid ethyl ester hydrochloride, the yield ranges from 88% to 96%, and the purity is greater than 98.5%.

[0179] 1.2 Synthesis of (2R,4S)-5-(biph...

Embodiment 2

[0185] Example 2 4(((2S,4R)-1-([1,1'-biphenyl]-4-yl)-5-ethoxy-4-methyl-5-oxopentane-2- Base) amino)-4-oxobutanoic acid ammonium synthesis:

[0186]

[0187] Add (2R,4S)-5-(biphenyl-4-yl)-4-[(3-carboxypropionyl)amino prepared according to the method of step 1.2 of Example 1 into a 1L three-necked flask equipped with mechanical stirring ]-2-methylpentanoic acid ethyl ester crude product (60.0g, 0.145mol) and acetone (720ml), stirring and dissolving at room temperature; cooling to 0-10°C for 5-10min, dropwise adding concentrated ammonia water (24.4g, 0.358mol), dropwise After the addition, continue to stir for 4h, filter, wash the filter cake with acetone (72ml), 10-30°C, -0.09~-0.1MPa, and vacuum-dry for 4-6h; 46.86g of solid 4-(((2S,4R)- Ammonium 1-([1,1'-biphenyl]-4-yl)-5-ethoxy-4-methyl-5-oxopentan-2-yl)amino)-4-oxobutanoate , that is, the compound of formula (A), the yield ranges from 70% to 75%, the purity is greater than 99.5%, the process repeatability is higher than...

Embodiment 3

[0188] The preparation of embodiment 3 formula (A) compound crystal form I

[0189]3.1 Weigh 20mg of the compound of formula (A) into a glass bottle, add acetonitrile (1ml), tetrahydrofuran (1ml), nitromethane (1ml), ethyl acetate (1ml), methyl tert-butyl ether (1ml) respectively , methyl isobutyl ketone (1ml), n-heptane (1ml), diethyl ether (1ml), dichloromethane (1ml), chloroform (1ml), isopropyl acetate (1ml), chloroform / methyl tert-butyl Ether (500μl / 500μl), isopropyl acetate / methyl tert-butyl ether (500μl / 500μl), dichloromethane / toluene (500μl / 500μl), acetonitrile / n-hexane (500μl / 500μl), nitromethane / n-hexane Alkane (500μl / 500μl), ethyl acetate / n-heptane (500μl / 500μl), methyl isobutyl ketone / n-heptane (500μl / 500μl), ethyl acetate / ether (500μl / 500μl), ethyl acetate / petroleum ether (500 μl / 500 μl), dichloromethane / petroleum ether (500 μl / 500 μl), stirred and equilibrated at 25°C for at least 24 hours, filtered, and the solid was dried in air for 10 minutes.

[0190] 3.2 ...

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 belongs to the field of chemical synthesis, and particularly relates to an ammonium carboxylate compound and crystal forms and amorphous substance thereof and preparation methods of thecompound, the crystal forms and the amorphous substance. The compound, the crystal form I of the compound, a single crystal, the amorphous substance and the crystal form II are prepared. The compound,the crystal forms, the single crystal and the amorphous substance can exist stably and present good solid forms and are applicable to medicine forming, and a product has high purity and contains fewsingle impurities. The preparation method adopts a concise process and is easy to implement, the reaction conditions are mild, and the product yield is high. A product does not need to be purified repeatedly, has high purity, is safe and environmentally friendly, and can be easily prepared by industrial production.

Description

[0001] This application claims the priority of the earlier application submitted to the State Intellectual Property Office of China on April 28, 2017, with the patent application number 201710300300.5, and the title of the invention being "Crystal form of compound, amorphous substance and its preparation method". The entirety of this application is incorporated by reference into this application. technical field [0002] The invention belongs to the field of chemical synthesis, and in particular relates to a carboxylate ammonium salt compound, its crystal form, an amorphous substance and a preparation method thereof. Background technique [0003] LCZ696, as the first dual-action angiotensin receptor-neprilysin inhibitor, has a new and unique mode of action, which can enhance the function of the cardioprotective neuroendocrine system (natriuretic peptide system) while inhibiting the harmful system (renin - the action of the angiotensin-aldosterone system), which is thought to...

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): C07C233/47C07C231/12A61P9/12A61P9/04
CPCA61P9/04A61P9/12C07C227/20C07C231/02C07C231/12C07C233/47C07B2200/13C07C229/34C07C231/24C07C235/74
Inventor 张波丁肖华戴冬成雷四军刘学明段盼盼陈永凯王朝东
Owner WUHAN LL SCI & TECH DEV
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com