Method for detecting enantiomer in Avapritinib intermediate

A technology for enantiomers and intermediates, which is applied in the field of detection of enantiomers in Avapritinib intermediates, achieving strong practicability, no tailing, and good detection results

Active Publication Date: 2021-11-23
HAINAN MEDICAL COLLEGE
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] There is no effective ((S)-1-(4-fluorophenyl)-1-[2-(piperazin-1-yl)pyrimidin-5-yl]ethylamine chiral effective control detection method in the prior art , Therefore, in order to continuously improve the safety and effectiveness of Avapritinib, it is urgent to establish a key intermediate (S)-1-(4-fluorophenyl)-1 in Avapritinib that is easy to operate, high in sensitivity and good in reproducibility. Quantitative detection method of enantiomers of -[2-(piperazin-1-yl)pyrimidin-5-yl]ethylamine

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
  • Method for detecting enantiomer in Avapritinib intermediate
  • Method for detecting enantiomer in Avapritinib intermediate
  • Method for detecting enantiomer in Avapritinib intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Select the content of (S)-1-(4-fluorophenyl)-1-[2-(piperazin-1-yl)pyrimidin-5-yl]ethylamine whose batch number is 20210421 for detection, including the following steps:

[0049] S1. Preparation of (S)-1-(4-fluorophenyl)-1-[2-(piperazin-1-yl)pyrimidin-5-yl]ethylamine test solution:

[0050] Weigh 10mg of (S)-1-(4-fluorophenyl)-1-[2-(piperazin-1-yl)pyrimidin-5-yl]ethanamine sample and add 10mL n-hexane-absolute ethanol solution, by It is prepared by mixing n-hexane and absolute ethanol with a volume ratio of 1:1. After mixing evenly, it is prepared to contain (S)-1-(4-fluorophenyl)-1-[2-(piperazine-1 -yl) pyrimidin-5-yl] ethylamine 1.0mg solution, as need testing solution, stand-by.

[0051] S2. Preparation of (R)-1-(4-fluorophenyl)-1-[2-(piperazin-1-yl)pyrimidin-5-yl]ethylamine reference substance stock solution:

[0052] Weigh (R)-1-(4-fluorophenyl)-1-[2-(piperazin-1-yl)pyrimidin-5-yl]ethylamine, accurately weigh 100mg, n-hexane-absolute ethanol solution Dissolve and...

Embodiment 2

[0065] Choose the (S)-1-(4-fluorophenyl)-1-[2-(piperazin-1-yl) pyrimidin-5-yl] ethylamine sample of the same batch as Example 1, to (R )-1-(4-fluorophenyl)-1-[2-(piperazin-1-yl)pyrimidin-5-yl]ethanamine peak purity is detected, the difference between the present embodiment and embodiment 1 is only : different detectors are used in the chromatographic conditions, and other detection conditions are consistent with embodiment 1. In this embodiment, the assay conditions of high performance liquid chromatography include:

[0066] Chromatographic column: CHIRALCEL*OD-H (model: length 250mm, inner diameter 4.6mm, cellulose surface covalently bonded silica gel filler, filler particle size 5μm);

[0067] Detector: DAD detector;

[0068] Detection wavelength: 220nm;

[0069] Column temperature: 30°C;

[0070] Flow rate: 1.0mL / min;

[0071] Mobile phase: Calculated by volume ratio, n-hexane:ethanol:isopropanol=99:0.5:0.5. It can be seen from the test that the peak purity of (S)-1-(...

Embodiment 3

[0073] Select (R)-1-(4-fluorophenyl)-1-[2-(piperazin-1-yl)pyrimidin-5-yl]ethanamine reference substance solution for detection limit and quantification limit detection, signal-to-noise ratio 10:1 is the quantification limit, and the signal-to-noise ratio is 3:1 is the detection limit. The detection conditions of this embodiment are consistent with those of Embodiment 1. In this embodiment, the assay conditions of high performance liquid chromatography include:

[0074] Chromatographic column: CHIRALCEL*OD-H (model: length 250mm, inner diameter 4.6mm, cellulose surface covalently bonded silica gel filler, filler particle size 5μm);

[0075] Detector: UV detector;

[0076] Detection wavelength: 220nm;

[0077] Column temperature: 30°C;

[0078] Flow rate: 1.0mL / min;

[0079] Mobile phase: Calculated by volume ratio, n-hexane:isopropanol:triethylamine=80:20:0.05.

[0080] After testing, it can be seen that the detection limit of (R)-1-(4-fluorophenyl)-1-[2-(piperazin-1-yl)py...

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
particle diameteraaaaaaaaaa
wavelengthaaaaaaaaaa
separationaaaaaaaaaa
Login to view more

Abstract

The invention provides a method for detecting an enantiomer of an Avapritinib key intermediate. The adopted chromatographic conditions are as follows: the chromatographic column is CHIRALCEL*OD-H 4.6*250 mm, 5 [mu]m, the column temperature is 30 DEG C, the detection wavelength is 220 nm, the mobile phase is normal hexane, ethanol and isopropanol in a ratio of (99-102):(0.1-1):0.5, and the flow velocity is 0.8-1.0 mL / min. By adopting the method, quantitative analysis of the enantiomer (R)-1-(4-fluorophenyl)-1-[2-(piperazine-1-yl)pyrimidine-5-yl]ethylamine in (S)-1-(4-fluorophenyl)-1-[2-(piperazine-1-yl)pyrimidine-5-yl]ethylamine can be accurately carried out, the enantiomer can be effectively separated and detected, the peak pattern is symmetrical, the tailing phenomenon is avoided, the separation degree, the specificity, the quantitation limit, the detection limit, the linearity, the repeatability, the accuracy degree, the precision, the solution stability and the durability all meet the requirements, and the detection effect is good.

Description

technical field [0001] The invention relates to the technical field of Avapritinib, in particular to a method for detecting enantiomers in Avapritinib intermediates. Background technique [0002] Avapritinib (Ava) is an oral, potent and highly selective tyrosine kinase inhibitor (tyrosinekinase inhibitors, TKI), developed by Blueprint Medicines, on January 9, 2020, the US Food and Drug Administration (FDA) ) is approved for listing. [0003] In the latest study of GIST patients with KIT / PDGFRα mutation, Ava has shown preliminary efficacy including patients with PDGFRα D842V mutation, and may become the first-line treatment drug for this mutation subgroup. The conventional dosage regimen of Ava is to take orally once a day on an empty stomach, 300 mg each time, until the patient’s disease progresses or unacceptable adverse reactions occur. The structural formula is shown in figure 1 . [0004] [0005] Its structural formula see figure 1 . [0006] Ava is a type I TKI...

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): G01N30/02G01N30/06G01N30/74
CPCG01N30/02G01N30/06G01N30/74
Inventor 陈年根
Owner HAINAN MEDICAL COLLEGE
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