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

Novel crystal form of neratinib maleate and preparation method thereof

A technology of maleate salt and maleic acid, which is applied in the field of chemical medicine, can solve the problems of unfavorable long-term storage, etc., and achieve the effects of increasing the dissolution rate, avoiding crystal transformation, and avoiding solubility

Inactive Publication Date: 2016-03-02
CRYSTAL PHARMATECH CO LTD
View PDF2 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But patent CN101918390B only discloses three crystal forms of maleate, wherein crystal form III is a partial hydrate (including mixed crystals of crystal form I and crystal form II); crystal form I is an anhydrate, but it is in the air It is easy to absorb water and convert to crystal form II, which is not conducive to long-term storage

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
  • Novel crystal form of neratinib maleate and preparation method thereof
  • Novel crystal form of neratinib maleate and preparation method thereof
  • Novel crystal form of neratinib maleate and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] The preparation method of formula (I) compound maleate crystal form A:

[0080] 101.2 mg of the compound of formula (I) was dissolved in 4 mL of dichloromethane, 73.3 mg of maleic acid was added, and the reaction was stirred at room temperature for 12 hours. The solid was collected by centrifugation and obtained.

[0081] The maleate product prepared by the above-mentioned method, its 1 The HNMR identification data are as follows, and the data show that the molar ratio of the compound of formula (I) to maleic acid is 1:3.

[0082] 1 HNMR(400MHz,DMSO-d6)δ9.81(s,1H),9.76(s,1H),8.95(s,1H),8.60(d,J=4.1Hz,1H),8.54(s,1H), 7.88(td, J1=7.7Hz, J2=1.7Hz, 1H), 7.59(d, J=7.8Hz, 1H), 7.37-7.42(m, 3H), 7.21-7.26(m, 2H), 6.82–6.70 (m,2H),6.20(s,6H),5.29(s,2H),4.33(q,J=6.9Hz,2H),3.96(d,J=5.4Hz,2H),2.81(s,6H) , 1.47 (t, J=6.9Hz, 3H).

[0083] After testing, the solid obtained in this example is crystal form A, and its X-ray powder diffraction data are shown in Table 1. Its XRPD p...

Embodiment 2

[0088] The preparation method of formula (I) compound maleate crystal form A:

[0089] 19.8 mg of the compound of formula (I) was added to 1 mL of acetone to prepare a suspension, 13.0 mg of maleic acid was added, and the reaction was stirred for 12 hours at room temperature. The solid was collected by centrifugation and obtained.

[0090] After testing, the solid obtained in this example is crystal form A, and its X-ray powder diffraction data are shown in Table 2.

[0091] Table 2

[0092] 2theta

[0093] 13.94

Embodiment 3

[0095] The preparation method of formula (I) compound maleate crystal form A:

[0096] Add 10.0 mg of the compound of formula (I) to 0.5 mL of isopropanol to make a suspension, add 6.0 mg of maleic acid, add n-hexane dropwise to 0.6 mL while stirring, after the dropwise addition is complete, stir the reaction at room temperature 12 hours. The solid was collected by centrifugation and obtained.

[0097] After testing, the solid obtained in this example is crystal form A, and its X-ray powder diffraction data are shown in Table 3.

[0098] table 3

[0099] 2theta

[0100] 12.25

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 relates to a novel crystal form of (2E)-N-{4-[3-chrolo-4-(2-methoxypyridine)aniline]-3-cyano-7-ethyoxyl-6-quinolyl}-4-(dimethylamino)-2-butene amide maleate and a preparation method thereof. The novel crystal form of the maleate of a compound with a formula (I) has the beneficial advantages of being high in dissolvability, good in stability, developable in technology, easy to process and the like; in addition, the preparation method is simple and low in cost and has the important value on optimization and development of the medicine in future.

Description

technical field [0001] The present invention relates to the field of chemical medicine, in particular to (2E)-N-{4-[3-chloro-4-(2-pyridylmethoxy)anilino]-3-cyano-7-ethoxy- A new crystal form of maleate salt of 6-quinolyl}-4-(dimethylamino)-2-butenamide and a preparation method thereof. Background technique [0002] Neratinib is an anti-breast cancer drug developed by Wyeth Pharmaceuticals, a subsidiary of Pfizer Pharmaceuticals in the United States, and then Puma Biotechnology Company (Puma) obtained a development license from Pfizer. It is an oral, irreversible, pan-ErbB receptor tyrosine kinase inhibitor, which can effectively inhibit the activity of ErbB1 and ErbB2 tyrosine kinases. The chemical name of neratinib is (2E)-N-{4-[3-chloro-4-(2-pyridylmethoxy)anilino]-3-cyano-7-ethoxy-6- Quinolinyl}-4-(dimethylamino)-2-butenamide, its structure is as shown in formula (I): [0003] [0004] At present, the patent CN101918390B discloses various salts of the compound of fo...

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): C07D401/12A61K31/4709A61P35/00
CPCA61K31/4709C07D401/12A61P35/00C07B2200/13C07C51/412C07C51/43C07C57/145
Inventor 陈敏华张炎锋刁小娟张晓宇
Owner CRYSTAL PHARMATECH 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