Novel method for catalytically synthesizing osimertinib intermediate with a graphene/Pd catalyst

A palladium catalyst and graphene technology, applied in organic chemistry and other fields, can solve problems such as complex conditions, high prices, and inapplicability to industrial production

Inactive Publication Date: 2018-03-02
UNIV OF JINAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0011] The conditions of this method are complicated, and the amount of catalyst palladium used is large, because of its high price, and cannot be recycled and reused, resulting in increased production costs, and the reaction time is long, so it is not suitable for large-scale industrial production

Method used

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  • Novel method for catalytically synthesizing osimertinib intermediate with a graphene/Pd catalyst
  • Novel method for catalytically synthesizing osimertinib intermediate with a graphene/Pd catalyst
  • Novel method for catalytically synthesizing osimertinib intermediate with a graphene/Pd catalyst

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Example 1: Mix 6.25 mL of 8 mg / mL graphene oxide aqueous slurry with 3 mL of 1 mg / mL palladium chloride aqueous solution, the mass ratio of graphene oxide to palladium chloride is 50:3, ultrasonically disperse, add 15 mg of oil Amine, under stirring, dropwise the 5mg / mL sodium borohydride solution of 2.5mL, the mass ratio of graphene oxide and sodium borohydride is 10:2.5, and the resulting product is centrifuged, washed, dried to obtain the graphene catalyst of supported palladium .

Embodiment 2

[0019] Example 2: Add N-benzyloxycarbonyl-2-methoxy-4-[2-dimethylaminoethylmethylamine]- 5-Nitroaniline (3.2g, 10mmol), graphene palladium catalyst (0.22g, 1mmol), water (5mL), irradiated with 500nm LED light, reacted for 15min, filtered, extracted with 15mL dichloromethane, and saturated The organic layer was washed with salt water, dried over anhydrous sodium sulfate, filtered, and finally dichloromethane was removed by rotary evaporation to obtain 2.83 g of a foamy off-white solid, with a yield of 96.9%.

Embodiment 3

[0020] Example 3: N-benzyloxycarbonyl-2-methoxy-4-[2-dimethylaminoethylmethylamine]- 5-Nitroaniline (3.2g, 10mmol), graphene palladium catalyst (0.22g, 1mmol), water (5mL), irradiated with 400nm LED light, reacted for 15min, filtered, extracted with 15 mL of dichloromethane, and used The organic layer was washed with saturated brine, dried, filtered, and finally dichloromethane was removed by rotary evaporation to obtain a foamy off-white solid (2.80 g), with a yield of 95.9%.

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Abstract

The invention discloses a novel method for catalytically synthesizing an osimertinib intermediate, [2-[2-dimethylamineethylmethylamine]-4-methoxy-5-benzyloxyamide]phenylamine, with a graphene / Pd catalyst. In the method, an osimertinib intermediate, N-carbobenzoxy-2-methoxy-4-[2-dimethylamineethylmethylamine]-5-nitrophenylamine, is used as a raw material; the nitro group then is reduced into an amino group by hydrogen under light irradiation with the graphene / Pd catalyst, thereby producing the [2-[2-dimethylamineethylmethylamine]-4-methoxy-5-benzyloxyamide]phenylamine, yield being higher than 95% and purity being higher than 98%. Compared with other methods, the method has gentle reaction conditions and is more environment-friendly and has simple operations; the reaction is more high-effective and rapid, and the catalyst has high wear resistance and recycle rate. The intermediate and the final product have high quality; the method has advantages in industrial production.

Description

technical field [0001] The invention belongs to the technical field of preparation of raw materials and pharmaceutical intermediates, and in particular relates to a preparation method for an intermediate of a new anti-non-small cell lung cancer drug osimertinib (AZD9291). Background technique [0002] Osimertinib (AZD9291) is a third-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor developed by AstraZeneca (AstraZeneca) for the activation of resistance mutant EGFR. In April 2014, the U.S. Food and Drug Administration (FDA) awarded the title of "Breakthrough Therapy Drug" to AZD9291. Targeted drugs for side effects such as rashes. [0003] The chemical name of AZD9291 is: N-{2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1H-ind Indol-3-yl)-2-pyrimidinyl]amino]phenyl}-2-acrylamide, its structural formula is. [0004] [0005] Osimertinib intermediate N-benzyloxycarbonyl-2-methoxy-4-[2-dimethylaminoethylmethylamine]-5-n...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/04
CPCC07D403/04
Inventor 郑庚修崔召新高令峰谷海洋
Owner UNIV OF JINAN
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