Preparation method for ceritinib

A technology of ceritinib and compound, applied in the field of ceritinib synthesis, can solve the problems of high time cost and raw material cost, difficult to show economic benefits, long operation cycle, etc., and achieves good application prospects, environmental friendliness, and operation. easy effect

Inactive Publication Date: 2018-10-23
SUZHOU BEC BIOLOGICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

It can be seen from the above that the reaction operation cycle of this step is long, the process is relatively complicated, the time cost and raw material cost are relatively high, and the economic benefits are difficult to show

Method used

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  • Preparation method for ceritinib
  • Preparation method for ceritinib
  • Preparation method for ceritinib

Examples

Experimental program
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Effect test

Embodiment 1

[0022] Under nitrogen protection, the compound (3.5g, 1eq) of formula (3), the compound (2.8g, 0.8eq) of formula (2) were added in diisopropylethylamine (16.8g), and the temperature was raised to 80 ℃ reaction, after the completion of the reaction, evaporate the organic base, add ethyl acetate to extract, wash with water, add hydrogen chloride in ethyl acetate solution, stir for 2 hours, filter to obtain a solid, adjust the base of the solid, and suction filter to obtain the compound of formula (1). Compound ceritinib (2.5 g).

Embodiment 2

[0024] Under the protection of nitrogen, the compound of formula (3) (3.5g, 1eq) and the compound of formula (2) (4.2g, 1.2eq) were added to 1,8-diazabicyclo[5.4.0]undeca- In 7-ene (50.4g), the temperature was raised to 120°C for reaction. After the reaction was completed, the organic base was evaporated, extracted with ethyl acetate, washed with water, added with ethyl acetate solution of hydrogen chloride, stirred for 2 hours, and filtered to obtain a solid. The solid was adjusted to base and suction filtered to obtain the compound ceritinib (3.2 g) of formula (1).

Embodiment 3

[0026] Under the protection of nitrogen, the compound of formula (3) (3.5g, 1eq) and the compound of formula (2) (3.5g, 1eq) were added to triethylenediamine (28g), and the temperature was raised to 90°C for reaction. After completion, evaporate the organic base, add ethyl acetate to extract, wash with water, add hydrogen chloride in ethyl acetate solution, stir for 2 hours, filter to obtain a solid, adjust the base of the solid, and suction filter to obtain the compound of formula (1) ceretyl Nil (1.8g).

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Abstract

The invention discloses a preparation method for ceritinib, which comprises the following steps: under nitrogen atmosphere, a compound shown as formula (2) and a compound shown as formula (3) are added into organic base, and temperature is increased to 80 DEG C to 120 DEG C for reaction. The organic base is diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undecy-7-ene, triethylene diamine or pyridine. The method disclosed by the invention is simple, environmentally friendly and easy to implement. (The reaction formula is 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 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 the structural formula of ceritinib. At present, the original research route is to generate Buchwald-Hartwig coupling between the compound of formula (2) and the compound of formula (3) under the action of palladium reagent and tetrahydrofuran as solvent. joint reaction. The reaction time of this step is very long. When the scale is enlarged to 10g, it basically needs to be refluxed in a tetrahydrofuran solvent for about a week. The p...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12
CPCC07D401/12
Inventor 李苏杨徐勤霞成清明
Owner SUZHOU BEC BIOLOGICAL TECH
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