2-phenyl propionic ester derivative and preparation method and application thereof

The technology of a drug and an alkyl group, which is applied in the field of new intermediates and their preparation, can solve the problems of many side reactions, difficult to obtain, etc., and achieves the effects of simple preparation and difficult to obtain raw materials.

Inactive Publication Date: 2015-11-04
CHONGQING HUAPONT PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, the raw material benzene derivative formula C of this method needs to be dimethylated in advance, is not easy to obtain, and has many side reactions

Method used

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  • 2-phenyl propionic ester derivative and preparation method and application thereof
  • 2-phenyl propionic ester derivative and preparation method and application thereof
  • 2-phenyl propionic ester derivative and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1 2-[4-[2-[4-[1-(2-ethoxyethyl)benzimidazol-2-yl]-1-piperidinyl]ethyl]phenyl]-propionic acid methyl Synthesis of esters

[0045] Add 8.24g of 4-[2-[4-[1-(2-ethoxyethyl)benzimidazol-2-yl]-1-piperidinyl]ethyl]chlorobenzene to 200ml N,N-di Add 2.12g of bipyridine nickel bromide and 0.09g of manganese dioxide (activated) to methylformamide, add 4.18g of methyl 2-bromopropionate in N,N-dimethyl Base formamide solution, after the dropwise addition was completed, the reaction was incubated at 100°C, and the reaction was stopped after the disappearance of one of the raw materials was detected by HPLC.

[0046] The reaction solution was filtered, 300ml of water and 200ml of ethyl acetate were added to the filtrate, the layers were separated, the organic layer was collected, concentrated, and passed through a silica gel chromatography column (gradient elution with dichloromethane:methanol=100:1 to 5:1), The product 2-[4-[2-[4-[1-(2-ethoxyethyl)benzimidazol-2-yl]-1-piper...

Embodiment 2

[0049] Example 2 2-[4-[2-[4-[1-(2-ethoxyethyl)benzimidazol-2-yl]-1-piperidinyl]ethyl]phenyl]-propionic acid ethyl Synthesis of esters

[0050] 9.13g of 4-[2-[4-[1-(2-ethoxyethyl)benzimidazol-2-yl]-1-piperidinyl]ethyl]bromobenzene was added to 400ml of acetonitrile, and 0.11 g bipyridine nickel bromide and 0.87g manganese dioxide (activated), add dropwise an acetonitrile solution containing 1.37g ethyl 2-chloropropionate at 50°C, and react at 50°C after the dropwise addition, HPLC method The reaction was stopped when the disappearance of one of the starting materials was detected.

[0051] The reaction solution was filtered, 400ml of water and 400ml of ethyl acetate were added to the filtrate, the layers were separated, the organic layer was collected, concentrated, and passed through a silica gel chromatography column (eluted with dichloromethane:methanol=100:1 to 5:1 gradient), The product 2-[4-[2-[4-[1-(2-ethoxyethyl)benzimidazol-2-yl]-1-piperidinyl]ethyl]phenyl]-propionic...

Embodiment 3

[0054] Example 3 2-[4-[2-[4-[1-(2-ethoxyethyl)benzimidazol-2-yl]-1-piperidinyl]ethyl]phenyl]-propionic acid iso Synthesis of Propyl Ester

[0055] Add 10.07g of 4-[2-[4-[1-(2-ethoxyethyl)benzimidazol-2-yl]-1-piperidinyl]ethyl]iodobenzene to 300ml ethylene glycol dimethyl In the ether, add 0.53g bipyridyl nickel bromide and 0.17g manganese dioxide (activated), add dropwise the ethylene glycol dimethyl ether solution containing 12.35g isopropyl 2-chloropropionate at 20°C, drop After the addition was completed, the reaction was incubated at 20°C, and the reaction was stopped after the disappearance of one of the raw materials was detected by HPLC.

[0056] The reaction solution was filtered, 200ml of water and 300ml of ethyl acetate were added to the filtrate, the layers were separated, the organic layer was collected, concentrated, and passed through a silica gel chromatography column (eluted with dichloromethane:methanol=100:1 to 5:1 gradient), The product 2-[4-[2-[4-[1-(2-etho...

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Abstract

The invention provides a preparation method of antihistamine medicine A. A new intermediate compound shown in a formula I is prepared and can serve as a raw material for the medicine A. A preparation method of the compound in the formula I is shown as follows: a compound in a formula II and a compound in a formula III react under the catalysis of manganese dioxide and dipyridyl nickel bromide. See the formulas in the specification.

Description

technical field [0001] The invention relates to a method for synthesizing antihistamines, a new intermediate in the synthesis method and a preparation method thereof. Background technique [0002] In the preparation of antihistamine drug A, dimethylated benzene derivatives (formula C) and benzimidazole derivatives (formula B) are traditionally used as raw materials for coupling followed by hydrolysis. [0003] Adopt this method exactly as CN1176964: [0004] [0005] However, the raw material benzene derivative formula C of this method needs to be dimethylated in advance, is not easy to obtain, and has many side reactions. Therefore, it is necessary to study a new preparation method. Contents of the invention [0006] The ultimate purpose of the present invention is to overcome the defects of the existing method for preparing antihistamine drug A, and adopt a completely different route from the traditional method. The direct purpose of the present invention is to syn...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/04
CPCC07D401/04
Inventor 罗炼杨华占肖
Owner CHONGQING HUAPONT PHARMA
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