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Clean production method of medicine ponatinib intermediate for treating leukemia

A technology of precursor and modified water, applied in chemical instruments and methods, preparation of organic compounds, preparation of amino compounds, etc., can solve the problems of low product yield and large environmental pollution, and achieve high product selectivity and enhanced conversion. rate, mild conditions

Inactive Publication Date: 2018-09-04
商立华
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The object of the invention is to overcome the problems of large environmental pollution and low product yield in the production process of 3-trifluoromethyl-4-[(4-methylpiperazin-1-yl) methyl]aniline in the prior art, Provided is a cerium-modified hectorite-supported Pd catalyst for catalyzing 4-(4-methylpiperazine-1-methylene)-3-trifluoromethyl-1-nitrobenzene to 3-trifluoro The process of methyl-4-[(4-methylpiperazin-1-yl)methyl]aniline, the catalytic process of the present invention is green, pollution-free, and the yield is high, suitable for industrial production, and meets the requirements of modern green chemical industry

Method used

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  • Clean production method of medicine ponatinib intermediate for treating leukemia
  • Clean production method of medicine ponatinib intermediate for treating leukemia
  • Clean production method of medicine ponatinib intermediate for treating leukemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Preparation of cerium-modified hectorite supported Pd catalyst:

[0043] 1) Preparation of cerium-modified hectorite material:

[0044] 1-1) Add 90mmol ethyl orthosilicate to 200ml ethanol, stir at room temperature for 15min; add dropwise 100ml MgCl with a concentration of 0.5mol / L 2 .6H 2 0 aqueous solution, stir at room temperature for 1-2 hours after the dropwise addition to form a uniform silicon-magnesium mixture; add 1mol / L ammonia solution to the silicon-magnesium mixture dropwise, adjust the pH to 11, and stir at 70°C for 1-2 days Si-Mg precipitates are formed;

[0045] 1-2) Cool down to room temperature, centrifuge at 1000rpm to obtain particles, disperse the particles into 300ml purified water, then add 10mmol LiOH and 5mmol Ce(NO 3 ) 3 .6H 2 O Stir evenly, add 1mol / L ammonia solution to adjust the pH to 11.0, stir evenly to obtain a solid dispersion, and then transfer the solid dispersion to a hydrothermal reaction kettle at 130-140 After hydrothermal r...

Embodiment 1-A

[0051] The hectorite-supported Pd catalyst was prepared by a single factor method, that is, no Ce(NO 3 ) 3 .6H 2 O, the rest are exactly the same as in Example 1, and the prepared catalyst is abbreviated as Pd / H.

Embodiment 2

[0053] The cerium-modified hectorite loaded Pd catalyst (abbreviated as Pd / Ce-H) prepared in Example 1, the cerium-modified hectorite material (abbreviated as Ce-H) and the Pd prepared in Example 1-A thereof / H and commercially available 10.0%wt Pd / C as catalysts (abbreviated as Pd / C), catalyzed 4-(4-methylpiperazine-1-methylene)-3-trifluoromethyl-1-nitro Benzene prepares 3-trifluoromethyl-4-[(4-methylpiperazin-1-yl) methyl] aniline, and the reaction conditions are as follows:

[0054] Catalytic hydrogen transfer: add substrate 4-(4-methylpiperazine-1-methylene)-3-trifluoromethyl-1-nitrobenzene (10mmol, 3.03g), 40ml of ethanol, formic acid into the reactor Ammonium (80mmol, 5.04g), catalyzer (181mg, 6.0%wt), be warming up to 60-70 ℃ of reaction, HPLC detects each catalyst reaction system reaction liquid situation, treats that when reaction reaches equilibrium, counts each catalytic system substrate 4-(4 - Conversion rate of methylpiperazine-1-methylene)-3-trifluoromethyl-1-ni...

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Abstract

The invention belongs to the technical field of organic catalysis and in particular relates to a clean production method of a medicine ponatinib intermediate for treating leukemia. According to the clean production method provided by the invention, cerium nitrate is used as a modifying agent and hectorite is modified through a co-precipitation method to obtain modified hectorite; then noble metalPd is loaded to obtain a cerium modified hectorite supported Pd catalyst. The catalyst prepared by the clean production method can be used for catalyzing 4-(4-methylpiperazine-1-methylene)-3-trifluoromethyl-1-nitrobenzene to prepare the medicine ponatinib intermediate for treating the leukemia, i.e., 3-trifluoromethyl-4-[(4-methylpiperazine-1-yl)methyl]aniline. The clean production method has theadvantages of green and pollution-free catalysis system and relatively high yield and has an industrialized production prospect.

Description

technical field [0001] The invention belongs to the technical field of organic catalysis, and in particular relates to a clean production method for an intermediate of ponatinib, a medicine for treating leukemia. Background technique [0002] Ponatinib is an oral multi-target tyrosine kinase inhibitor developed by Ariad Company of the United States, which can effectively inhibit the activities of Bcr-Abl (including T315I mutation), Flt-3 and Src kinases. It is currently the only marketed drug that is effective against the BCR-ABL kinase T315I mutant strain, and is used to treat adult T315I-positive chronic myeloid leukemia (CML), or T315I-positive Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL); also for the treatment of CML and Ph in adults who have not been treated with other tyrosine kinase inhibitors + ALL. Ponatinib was approved for marketing in the United States on December 14, 2012, in Europe on July 1, 2013, and in Japan on September 28, 20...

Claims

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Application Information

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IPC IPC(8): B01J23/63B01J37/03B01J37/10B01J37/02B01J37/16C07C209/32C07C211/52
CPCB01J23/63B01J37/0201B01J37/031B01J37/10B01J37/16C07C209/325C07C211/52
Inventor 商立华文向东王骏陈阿亮张建帅
Owner 商立华
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