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Novel crystal form of osimertinib monohydrate

A technology of monohydrate and crystal form, which is applied in the field of osimertinib monohydrate crystal form, which can solve the problems of high humidity, easy deliquescence, high toxicity, and unsuitability for drug synthesis

Active Publication Date: 2021-09-10
LUNAN PHARMA GROUP CORPORATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, mesylate has the problems of high toxicity, high hygroscopicity and high humidity and is easy to deliquesce, so it is not suitable for use in pharmaceuticals under selective conditions.

Method used

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  • Novel crystal form of osimertinib monohydrate
  • Novel crystal form of osimertinib monohydrate
  • Novel crystal form of osimertinib monohydrate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] (1) 10.0 g of N-[2-[[2-(dimethylamino)ethyl](methyl)amino]-4-methoxy-5-[[4-(1-methyl-1H -Indol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide was added to 70mL of acetonitrile, slowly heated to 50°C until the solution was dissolved;

[0056] (2) Add the dissolved clear solution dropwise to 14 mL of purified water, stirring while adding;

[0057] (3) Slowly lower the temperature to 25°C, and control the temperature for crystallization for 5 hours;

[0058] (4) Vacuum drying was carried out for 5 hours after the crystallization was completed, the drying temperature was 35°C, the yield was 97.23%, HPLC: 99.98%.

Embodiment 2

[0060] (1) 10.0 g of N-[2-[[2-(dimethylamino)ethyl](methyl)amino]-4-methoxy-5-[[4-(1-methyl-1H Add -indol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide into 80mL of ethanol, slowly heat to 55°C, and wait for the solution to dissolve;

[0061] (2) Add the dissolved clear solution dropwise to 12 mL of purified water, stirring while adding;

[0062] (3) Slowly lower the temperature to 30°C, and control the temperature for crystallization for 6 hours;

[0063] (4) Vacuum drying was carried out for 7 hours after the crystallization was completed, the drying temperature was 35°C, the yield was 96.57%, HPLC: 99.98%.

Embodiment 3

[0065] (1) 10.0 g of N-[2-[[2-(dimethylamino)ethyl](methyl)amino]-4-methoxy-5-[[4-(1-methyl-1H -Indol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide was added to 50mL methanol, slowly heated to 45°C until the solution was dissolved;

[0066] (2) Add the dissolved clear solution dropwise to 17mL of purified water, stirring while adding;

[0067] (3) Slowly lower the temperature to 15°C, and control the temperature for crystallization for 4 hours;

[0068] (4) Vacuum drying was carried out for 5 hours after the crystallization was completed, the drying temperature was 30°C, the yield was 95.84%, HPLC: 99.97%.

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Abstract

The invention belongs to the technical field of crystal forms of organic medicines, and discloses a novel crystal form of osimertinib monohydrate. According to the novel crystal form of the osimertinib monohydrate, Cu-K alpha radiation is used, and an X-ray diffraction spectrum represented by 2[theta] has characteristic diffraction peaks at the positions of 5.9 + / -0.2 degrees, 7.3 + / -0.2 degrees, 9.1 + / -0.2 degrees, 11.2 + / -0.2 degrees, 25.2 + / -0.2 degrees and 25.41 + / -0.2 degrees. Compared with the prior art, the crystal form provided by the invention is simple in preparation method and low in cost, and has important value for optimization and development of the medicine in the future. The novel crystal form prepared by the invention of the osimertinib monohydrate has the advantages of high yield, high purity, good stability and good dissolution rate.

Description

technical field [0001] The invention belongs to the technical field of crystal forms of organic medicines, in particular to a crystal form of osimertinib monohydrate. Background technique [0002] Osimertinib, its chemical name is: N-[2-[[2-(dimethylamino)ethyl](methyl)amino]-4-methoxy-5-[[4-(1-methyl Base-1H-indol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide, its molecular formula is: C 28 h 33 N 7 o 2 , Molecular weight: 499.61. The structure is shown in Formula 1: [0003] [0004] Osimertinib is the third-generation oral, irreversible and selective EGFR mutation inhibitor developed by AstraZeneca. On November 13, 2015, the U.S. FDA approved its marketing in advance in the form of accelerated approval. Osimertinib is also the first in China. The first approved tumor drug for EGFR T790M mutation-positive locally advanced or metastatic non-small cell lung cancer. [0005] Targeted therapy for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/04
CPCC07D403/04C07B2200/13
Inventor 翟立海黄超张纪云郭立红刘忠
Owner LUNAN PHARMA GROUP CORPORATION