A kind of method for preparing gliquidone intermediate

A technology of gliquidone and intermediates, which is applied in the field of pharmaceutical chemical synthesis, and can solve problems such as safety, hidden dangers in operation, high reaction temperature, and harsh heating conditions

Active Publication Date: 2019-06-25
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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  • A kind of method for preparing gliquidone intermediate
  • A kind of method for preparing gliquidone intermediate
  • A kind of method for preparing gliquidone intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] S1: Add 50.00g of 2-carboxymethyl-5-methoxybenzoic 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 2h ; After reflux for 2 hours, cool down slightly until no more reflux, install a distillation device, heat up and steam to remove the remaining thionyl chloride, and after 30 minutes, remove the distillation device and use reduced pressure distillation to remove the remaining traces of dichloride in the three-necked flask. sulfoxide, until a small amount of white flocculent solids appear on the condenser, stop heating, wait for the temperature to drop to room temperature, add 200.0mL dichloromethane solution in the reaction flask, fully stir until the solid dissolves, and obtain the dichloromethane of intermediate (II). Chloromethane solution;

[0035] S2: Add 42.86 g of p-aminoethylbenzenesulfonamide to the intermediate (...

Embodiment 2

[0039] S1: Add 50.00g of 2-carboxymethyl-5-methoxybenzoic acid and 70.21g of thionyl chloride to a 500mL three-necked flask in sequence, start stirring, turn on heating, raise the temperature to reflux temperature of 79±1°C, and continue the reflux reaction 1h; after reflux for 1h, lower the temperature slightly until no more reflux, install a distillation device, raise the temperature and heat to evaporate the remaining thionyl chloride, and after 30 minutes, remove the distillation device and use reduced pressure distillation to remove the remaining trace dichloride in the three-necked flask. Thionyl chloride, until a small amount of white flocculent solids appear on the condenser, stop heating, wait for the temperature to drop to room temperature, add 200.0mL dichloromethane solution in the reaction flask, fully stir until the solid dissolves, and obtain the intermediate (II) Dichloromethane solution;

[0040] S2: Add 45.27 g of p-aminoethylbenzenesulfonamide to the interme...

Embodiment 3

[0042]S1: Add 50.00g of 2-carboxymethyl-5-methoxybenzoic acid and 64.90g of thionyl chloride to a 500mL three-necked flask in sequence, start stirring, turn on heating, raise the temperature to reflux temperature of 79±1°C, and continue the reflux reaction 10h; after reflux for 10h, lower the temperature slightly until no more reflux, install a distillation device, heat up and heat to evaporate the remaining thionyl chloride, and after 30 minutes, remove the distillation device, and use reduced pressure distillation to remove the remaining trace dichloride in the three-necked bottle. Thionyl chloride, until a small amount of white flocculent solids appear on the condenser, stop heating, wait for the temperature to drop to room temperature, add 200.0mL dichloromethane solution in the reaction flask, fully stir until the solid dissolves, and obtain the intermediate (II) Dichloromethane solution;

[0043] S2: Add 44.07 g of p-aminoethylbenzenesulfonamide to the intermediate (II) ...

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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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Patent Type & Authority Patents(China)
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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