Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Preparation method of high-purity crystal

A technology of crystallization and concentration, applied in the field of preparation of high-purity crystallization, can solve problems such as unfavorable commercial production, cumbersome operation, generation of genotoxic impurities, etc., to avoid genotoxic impurities, simple operation, and reduce impurity A and impurity B. produced effect

Pending Publication Date: 2022-02-01
2Y CHEM
View PDF6 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0018] Due to the shortcomings of the above three methods, which are too cumbersome to operate, potentially produce genotoxic impurities and degrade impurities A and B, it is not conducive to commercial production

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
  • Preparation method of high-purity crystal
  • Preparation method of high-purity crystal
  • Preparation method of high-purity crystal

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Embodiment 1: the preparation of lenvatinib mesylate crude product

[0053]

[0054] Add lenvatinib free base (1 g, 2.34 mmol) to N,N-dimethylformamide (10 mL), and heat to 90° C. to dissolve. After cooling to -20°C, a solution of methanesulfonic acid (0.23 g, 2.34 mmol) in methyl tert-butyl ether (10 mL) was added dropwise. After the addition, keep stirring for 2 hours. Filtration, the filter cake was washed with methyl tert-butyl ether, dried to obtain lenvatinib mesylate crude product (1.16g), the yield was 94.6%, the purity was 99.8%, impurity A: 0.08%, impurity B: 0.05 %.

[0055] H-NMR (600MHz, DMSO-d6): δMSO-(d, 1H), 8.73(s, 1H), 8.38(d, 1H), 8.09(s, 1H), 7.96(d, 2H), 7.66(s ,1H), 7.65(d,1H), 7.37(dd,1H), 7.27(m,1H), 6.96(d,1H), 4.09(s,3H), 2.69(m,1H), 2.36(s, 3H), 0.68 (m, 2H), 0.44 (s, 2H).

Embodiment 2

[0056] Embodiment 2: the preparation of lenvatinib mesylate crude product

[0057] Add lenvatinib (1 g, 2.34 mmol) into dimethyl sulfoxide (10 mL), and heat to 70° C. to dissolve. After cooling to 20°C, a solution of methanesulfonic acid (0.21 g, 2.22 mmol) in ethyl acetate (10 mL) was added dropwise. After the addition, keep stirring for 2 hours. After filtering, the filter cake was washed with ethyl acetate and dried to obtain lenvatinib mesylate crude product (1.10 g), with a yield of 90.1%, a purity of 99.9%, impurity A: 0.05%, and impurity B: 0.05%.

Embodiment 3

[0058] Embodiment 3: the preparation of lenvatinib mesylate crude product

[0059] Add lenvatinib (1 g, 2.34 mmol) into N-methylpyrrolidone (10 mL), and heat to 80° C. to dissolve. After cooling to 0°C, a solution of methanesulfonic acid (0.21 g, 2.22 mmol) in n-butyl acetate (10 mL) was added dropwise. After the addition, keep stirring for 2 hours. After filtering, the filter cake was washed with ethyl acetate and dried to obtain the crude product of lenvatinib mesylate (1.14 g), with a yield of 93.0%, a purity of 99.8%, impurity A: 0.05%, and impurity B: 0.04%.

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 provides a preparation method of a high-purity crystal, and particularly relates to a preparation method of a mesylate lenvatinib crystal C. The preparation method comprises the following steps: 1) dissolving a lenvatinib free alkali in a good solvent to obtain a solution of the lenvatinib free alkali; 2) clarifying and filtering the solution obtained in the step 1), adding methanesulfonic acid and a poor solvent I or a solution of methanesulfonic acid in the poor solvent I, and carrying out a salt forming reaction to obtain a crude product of the mesylate lenvatinib; 3) putting the obtained crude product of the mesylate into a poor solvent II, and pulping to obtain a mesylate crystal C. The purity of the obtained mesylate crystal C is not lower than 99.5%, the purity of any single impurity is not higher than 0.10%, and the total impurity is not higher than 0.5%. The purity of the lenvatinib mesylate crystal C prepared by the preparation method of the lenvatinib mesylate crystal C is higher, wherein, the contents of an impurity A and an impurity B in the lenvatinib mesylate crystal C are greatly reduced.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a preparation method of high-purity crystals. Background technique [0002] Lenvatinib mesylate, the Chinese chemical name is 4-[3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy]-7-methoxy-6-quinoline carboxamide methanesulfonate , the English chemical name is: 4-(3-Chloro-4-(3-cyclopropylureido)phenoxy)-7-methoxyquinoline-6-carboxamid e Mesylate, the trade name is Lenvanix, and its structure is as follows: [0003] [0004] Lenvatinib mesylate is a receptor tyrosine kinase (RTK) inhibitor that inhibits VEGFR1, VEGFR2, and VEGFR3. Lenvatinib mesylate (Lenvatinib) can also inhibit other RTKs associated with pathological neovascularization, tumor growth and cancer progression, including fibroblast growth factor (FGF) receptors FGFR1,2,3,4; platelet derivation Growth factor receptor alpha (PDGFRα), KIT and RET. Lenvatinib combined with everolimus (everolimus) can inc...

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): C07D215/48C07C309/04C07C303/32C07C303/44
CPCC07D215/48C07C309/04C07C303/32C07C303/44C07B2200/13
Inventor 何训贵袁明勇张恒彬周岩锋王元
Owner 2Y CHEM
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
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