Larotrectinib hydrochloride, and preparation method and application thereof

A technology for larotrectinib hydrochloride and larotrectinib hydrochloride, which is applied in the field of medicinal chemistry, can solve the problems of inability to form a good solid powder crystal form, and achieves the effects of good stability and simple preparation method

Inactive Publication Date: 2020-10-13
安庆多辉生物科技有限公司
View PDF7 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is that the free base of larotretinib in the prior art can not form better solid powder crystal form in conventional solvents, and a kind of larotretinib hydrochloride is provided

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
  • Larotrectinib hydrochloride, and preparation method and application thereof
  • Larotrectinib hydrochloride, and preparation method and application thereof
  • Larotrectinib hydrochloride, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] 500g of (3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-A]pyrimidine-3- Base]-3-hydroxyl-1-pyrrolidinecarboxamide was dissolved in 3000ml of ethanol, cooled to 5°C with stirring, and 120ml of concentrated hydrochloric acid (mass fraction was 36%) was added dropwise. 5h, suction filtration to obtain (3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-A]pyrimidine- I-HC crystal form of 3-yl]-3-hydroxy-1-pyrrolidinecarboxamide hydrochloride 520g yellow solid powder.

Embodiment 2

[0047] 5g of (3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-A]pyrimidine-3- Base]-3-hydroxy-1-pyrrolidinecarboxamide was dissolved in 20ml of ethanol, stirred and cooled down to -5°C, added 1.5ml of concentrated hydrochloric acid, kept stirring at 20°C for 4h, and obtained (3S)-N-[ 5-[(2R)-2-(2,5-Difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-A]pyrimidin-3-yl]-3-hydroxy-1-pyrrole I-HC crystal form of alkanecarboxamide hydrochloride 5.1g yellow solid powder.

Embodiment 3

[0049]50g of (3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-A]pyrimidine-3- Base]-3-hydroxy-1-pyrrolidinecarboxamide was dissolved in 250ml of isopropanol, stirred and cooled down to 0°C, added 20ml of concentrated hydrochloric acid, kept stirring at 18°C ​​for 2h, and obtained (3S)-N-[ 5-[(2R)-2-(2,5-Difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-A]pyrimidin-3-yl]-3-hydroxy-1-pyrrole I-HC crystal form of alkanecarboxamide hydrochloride 45g yellow solid powder.

[0050] (1) Characterization:

[0051] figure 2 (3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-A]pyrimidin-3-yl] -XRPD pattern of 3-hydroxy-1-pyrrolidinecarboxamide hydrochloride (larotrenib hydrochloride) (I-HC crystal form). PeakSearch Report(37Peaks, Max P / N=16.4)[H371.raw]a PEAK: 19-pts / Parabolic Filter, Threshold=9.0, Cutoff=2.0%, BG=7 / 1.0, Peak-Top=Summit.

[0052] Table 1 is the X-ray diffraction chart of the crystal form of larotrectinib hydrochloride. image 3 (3S)-N...

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

PropertyMeasurementUnit
quality scoreaaaaaaaaaa
Login to view more

Abstract

The invention discloses larotrectinib hydrochloride, belonging to the technical field of medicinal chemistry. The structural formula of the larotrectinib hydrochloride is as shown in the specification. The invention also discloses a preparation method of the larotrectinib hydrochloride. The preparation method comprises the following steps: dissolving (3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-A]pyrimidin-3-yl]-3-hydroxyl-1-pyrrolidinecarboxamide in an alcohol solvent, adding hydrochloric acid, carrying out cooling, conducting stirring to separate out a solid, and performing filtering to obtain the larotrectinib hydrochloride. The preparation method disclosed by the invention has the beneficial effects that the preparation method is simple, the larotrectinib hydrochloride is prepared on the basis of conventional larotrectinib, and the larotrectinib hydrochloride is good in stability and applicable as a bulk drug form for research, development and production of preparations.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a larotrectinib hydrochloride, a crystal form of larotrectinib hydrochloride and a preparation method thereof. Background technique [0002] (3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-A]pyrimidin-3-yl]- 3-Hydroxy-1-pyrrolidine carboxamide, English name Larotrectinib, Chinese name Larotrectinib, is an anticancer drug approved by the US FDA in November 2018. The trade name is Vitrakvi. It is a powerful, oral, Selective inhibitor of tropomyosin receptor kinases (TRKs), effective against up to 17 types of cancer. It can be used to treat adults and children with locally advanced or metastatic solid tumors carrying NTRK gene fusions. Larotrectinib can be used for treatment as long as there are NTRK gene fusions, regardless of the region where the cancer occurs. [0003] The drug was jointly developed and marketed by Loxo Oncology of the United Stat...

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): C07D487/04A61K31/519A61P35/00
CPCA61P35/00C07B2200/13C07D487/04
Inventor 赵跃陈晨陈力万新锋王杰明周深程壮壮
Owner 安庆多辉生物科技有限公司
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