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Method for preparing gliquidone intermediate

A technology of glipaquinone and intermediates, applied in the field of medicinal chemistry synthesis, can solve the problems of safety, hidden dangers of operation, high reaction temperature, harsh heating conditions and the like

Active Publication Date: 2017-05-24
天津药物研究院药业有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Its existing problems are, one: the reaction temperature is too high (T=200 ℃), only limited to heating in the laboratory by a high-temperature cycler, and the heating conditions are harsh; The requirements for the equipment itself are very high, and electric heating must be used in production at a temperature of 200°C, which has high requirements for the structure of the reactor itself, and because it is a high-temperature reaction, there are great hidden dangers in terms of safety and operation.

Method used

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  • Method for preparing gliquidone intermediate
  • Method for preparing gliquidone intermediate
  • Method for preparing gliquidone intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] S1: Add 50.00g of acrylic acid and 58.88g of thionyl chloride to a 500mL three-necked flask in turn, start stirring, turn on heating, raise the temperature to reflux temperature of 79±1°C, and continue the reflux reaction for 2 hours; after reflux for 2 hours, cool down slightly until no more reflux , install the distillation device, heat up and evaporate the remaining thionyl chloride, and after 30 minutes, remove the distillation device and change to vacuum distillation to distill the remaining traces of thionyl chloride in the three-necked flask until a small amount of white flocs appear on the condenser. until the solid is formed, stop heating, wait for the temperature to drop to room temperature, add 200.0mL dichloromethane solution to the reaction flask, stir well until the solid dissolves, and obtain the dichloromethane solution of intermediate (II);

[0035] S2: Add 42.86 g of p-aminoethylbenzenesulfonamide to the intermediate (II) dichloromethane solution obtain...

Embodiment 2

[0039] S1: Add 50.00g of acrylic acid and 70.21g of thionyl chloride to a 500mL three-necked flask in turn, start stirring, turn on heating, raise the temperature to reflux temperature of 79±1°C, and continue reflux reaction for 1h; after reflux for 1h, cool down slightly until no more reflux , install the distillation device, heat up and evaporate the remaining thionyl chloride, and after 30 minutes, remove the distillation device and change to vacuum distillation to distill the remaining traces of thionyl chloride in the three-necked flask until a small amount of white flocs appear on the condenser. until the solid is formed, stop heating, and when the temperature drops to room temperature, add 200.0mL of dichloromethane solution to the reaction flask, fully stir until the solid dissolves, and obtain the dichloromethane solution of intermediate (II);

[0040] S2: Add 45.27 g of p-aminoethylbenzenesulfonamide to the intermediate (II) dichloromethane solution obtained in step S...

Embodiment 3

[0042]S1: Add 50.00g of acrylic acid and 64.90g of thionyl chloride to a 500mL three-necked flask in turn, start stirring, turn on heating, raise the temperature to reflux temperature of 79±1°C, and continue the reflux reaction for 10h; after reflux for 10h, cool down slightly until no more reflux , install the distillation device, heat up and steam the remaining thionyl chloride, and after 30 minutes, remove the distillation device and use reduced pressure distillation to distill the remaining traces of thionyl chloride in the three-necked bottle until a small amount of white flocs appear on the condenser. until the solid is formed, stop heating, and when the temperature drops to room temperature, add 200.0mL dichloromethane solution in the reaction flask, fully stir until the solid dissolves, and obtain the dichloromethane solution of intermediate (II);

[0043] S2: Add 44.07 g of p-aminoethylbenzenesulfonamide to the intermediate (II) dichloromethane solution obtained in ste...

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Abstract

The invention belongs to the technical field of chemical synthesis of medicaments, and particularly relates to a method for preparing a gliquidone intermediate shown as a formula (I). The method comprises the following steps: S1, making 2-carboxymethyl-5-methoxy-benzoic acid react in the presence of thionyl chloride to generate an intermediate shown as a formula (II); S2, making the intermediate shown as the formula (II) react with p-amino ethyl benzene sulfonamide in the presence of triethylamine in a dichloromethane solvent to generate the gliquidone intermediate shown as the formula (I): 4-[2-(3,4-dihydro-7- methoxy-1,3-dioxo-2(1H)-isoquinolyl)ethyl]benzene sulfonamide. All the steps in the method are performed at the temperature of 100 DEG C or lower, so that industrial expanded production is facilitated.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and in particular relates to a method for preparing a gliquidone intermediate. Background technique [0002] Existing preparation structural formula is that the preparation method of the gliquidone intermediate of formula (I) mostly adopts the synthetic route that two compounds carry out melting reaction under high temperature environment (T=200 ℃), as follows: [0003] [0004] The characteristic of this synthesis method is that no solvent is used, the two substrates are directly transformed from solid to molten state at high temperature (200°C), and then react with each other, and finally the product is obtained by dissolving and extracting with an organic solvent. Its existing problems are, one: the reaction temperature is too high (T=200 ℃), only limited to heating in the laboratory by a high-temperature cycler, and the heating conditions are harsh; The requireme...

Claims

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Application Information

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IPC IPC(8): C07D217/24
CPCC07D217/24
Inventor 许海涛王凯任晓峰岳金龙李果赵钊张宁赵欣李惠龙
Owner 天津药物研究院药业有限责任公司
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