Unlock instant, AI-driven research and patent intelligence for your innovation.

Synthesis method of ceritinib intermediate

A technology of ceritinib and its synthetic method, which is applied in the field of synthesis of ceritinib intermediates, can solve problems such as difficult confirmation of effective dose, flammability of sodium and hydrogen, complex reactions, etc., and achieve good application prospects, environmental friendliness, and easy operation easy effect

Inactive Publication Date: 2018-10-26
SUZHOU BEC BIOLOGICAL TECH
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The compound of formula (1) is an important intermediate for the synthesis of ceritinib. At present, the original research route is to use sodium hydrogen as the base, dimethylformamide and dimethyl sulfoxide as the solvent, react at 0°C, and pass through the column after the reaction is completed. Purification obtains the compound of formula (1), and this method has following disadvantages, the first is that sodium hydrogen is very flammable when meeting water, brings considerable difficulty to amplification, and effective amount is difficult to confirm; The second is to use hydrophilic dihydrogen Methylformamide and dimethyl sulfoxide are used as solvents, which bring a lot of repetitive work during extraction; the third is that the reaction is relatively complicated and it is difficult to complete the reaction. Recrystallization can only be performed after column purification

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
  • Synthesis method of ceritinib intermediate
  • Synthesis method of ceritinib intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Under the protection of nitrogen, the compound of formula (3) (1.9g, 1eq), the compound of formula (2) (1.8g, 1eq) and 1,8-diazabicyclo[5.4.0]undeca-7- Alkene (0.38g, 0.25eq) was added to acetonitrile (1.9g), and the temperature was raised to 50°C for reaction. After the reaction was completed, it was naturally cooled to 35°C, added methanol (1.9g) and stirred for 5 hours, cooled to room temperature, and pumped The ceritinib intermediate compound (0.58 g) of formula (1) was obtained by filtration.

Embodiment 2

[0031] Under nitrogen protection, the compound of formula (3) (1.9g, 1eq), the compound of formula (2) (7.2g, 4eq) and diisopropylethylamine (0.32g, 0.75eq) were added to tetrahydrofuran (5.7g ), the temperature was raised to 100°C for reaction, after the reaction was completed, naturally cooled to 45°C, added ethanol (16.1g) and stirred for 24 hours, cooled to room temperature, and suction filtered to obtain the ceritinib intermediate compound of formula (1) (0.48g).

Embodiment 3

[0033] Under the protection of nitrogen, the compound of formula (3) (1.9g, 1eq), the compound of formula (2) (3.8g, 2eq) and 1,8-diazabicyclo[5.4.0]undeca-7- Alkene (0.76g, 0.5eq) was added to tetrahydrofuran (3.8g), and the temperature was raised to 70°C for reaction. After the reaction was completed, it was naturally cooled to 40°C, added with isopropanol (7.6g) and stirred for 12 hours, then cooled to room temperature , suction filtration to obtain the ceritinib intermediate compound (0.73g) of formula (1).

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 discloses a synthesis method of a ceritinib intermediate. The synthesis method comprises the following steps: under an inert gas atmosphere, adding a compound shown as a formula (3), a compound shown as a formula (2) and organic alkali into an organic solvent; raising the temperature to 100 DEG C from 50 DEG C and reacting to obtain a compound shown as a formula (1). The mol ratio ofthe compound shown as the formula (2) to the compound shown as the formula (3) ranges from (1 to 1) to (1 to 4); the organic alkali is diisopropylethylamine or 1,8-diazabicyclo[5.4.0]undecarbone-7-ene; the mol ratio of the organic alkali to the compound shown as the formula (3) ranges from (0.25 to 1) to (1 to 1); the organic solvent is tetrahydrofuran or acetonitrile; the mass of the organic solvent is 1 to 3 times as much as the mass of the compound shown as the formula (3). The formula (1), the formula (2) and the formula (3) are shown in the description.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to the field of organic drug synthesis, in particular to a synthesis method of an intermediate of ceritinib. Background technique [0002] Ceritinib was first approved as a second-line treatment for patients with ALK-positive NSCLC in 2015. Previously, these patients would first receive Pfizer / Merck's ALK inhibitor crizotinib. Therefore, once successfully approved, Novartis' drug can directly treat newly diagnosed NSCLC patients. [0003] The compound of formula (1) is an important intermediate for the synthesis of ceritinib. At present, the original research route is to use sodium hydrogen as the base, dimethylformamide and dimethyl sulfoxide as the solvent, react at 0°C, and pass through the column after the reaction is completed. Purification obtains the compound of formula (1), and this method has following disadvantages, the first is that sodium hydrogen is very flammable when...

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): C07D239/42
CPCC07D239/42
Inventor 李苏杨徐勤霞成清明
Owner SUZHOU BEC BIOLOGICAL TECH