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Method for preparing daclatasvir

A technology for finished products and compounds of viril, applied in the field of preparation of daclatasvir, which can solve the problem of low yield of daclatasvir

Inactive Publication Date: 2018-05-25
SUNSHINE LAKE PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The prior art shows that the yield of daclatasvir is not high, so the preparation process of daclatasvir needs to be further improved

Method used

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  • Method for preparing daclatasvir
  • Method for preparing daclatasvir
  • Method for preparing daclatasvir

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Feed intake 5g of the compound shown in formula II, 3.5g of the compound shown in formula III, add 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride of 2.5 times the molar amount of the compound shown in formula II Salt and dichloromethane 20ml, HPLC detection reaction. After the reaction (the compound shown in formula II≤0.5%), add 10ml of ammonia water, react at 30°C for 1h, and detect the reaction by thin-layer chromatography (developing solvent is dichloromethane:methanol=8:1), and wait for the reaction shown in formula 1 After the compound and the compound shown in formula 2 are completely converted (the compound shown in formula 1 and the compound shown in formula 2 are both ≤0.5%) into daclatasvir, add 30ml of dichloromethane and 25ml of water, extract and separate, and separate to obtain the organic phase After the organic layer was concentrated to dryness, the finished product of daclatasvir was obtained: 6.38g, the yield was 98.5%, and the HPLC purity...

Embodiment 2

[0049] Feeding 5g of the compound shown in the formula II, 3.5g of the compound I shown in the formula II, adding 2.5 times the molar amount of the compound shown in the formula II 1-ethyl-(3-dimethylaminopropyl) carbodiimide salt Acetate and methanol 20ml, HPLC detection reaction. After the reaction (the compound shown in formula II≤0.5%), add 10ml of diisopropylethylamine, react at 30°C for 3h, and detect the reaction by thin-layer chromatography (developing agent is dichloromethane:methanol=8:1), After compound formula 1 and compound formula 2 are completely converted (the compound shown in formula 1 and the compound shown in formula 2 are both ≤0.5%) into daclatasvir, add ethyl acetate 30mL and water 20mL, extract and separate liquid, and separate to obtain organic Phase, after the organic layer was concentrated to dryness, the finished product of daclatasvir was obtained: 6.32g, the yield was 97.5%, and the HPLC purity was 99.47%.

Embodiment 3

[0051]Feed intake 5g of compound shown in formula II, compound I shown in g formula II, add the 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride of 2.5 molar amounts of compound shown in formula II And acetone 20ml, HPLC detects reaction. After the reaction (the compound shown in formula II≤0.5%), add sodium hydroxide (2.1g, 6eq), react at 20°C for 1.5h, thin-layer chromatography (developing solvent is dichloromethane:methanol=8:1) Detection reaction, after compound formula 1 and compound formula 2 are completely converted (the compound shown in formula 1 and the compound shown in formula 2 are both ≤0.5%) into daclatasvir, add 30mL of isopropyl acetate and 25mL of water, extract and separate , separated to obtain the organic phase, and the organic layer was concentrated to dryness to obtain the finished product of daclatasvir: 6.41g, the yield was 99.0%, and the HPLC purity was 99.48%.

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Abstract

The invention provides a method for preparing daclatasvir and belongs to the field of pharmaceutical and chemical industry. According to the method, a compound shown in a formula II and a compound shown in a formula III are subjected to a condensation reaction, a mixture A is obtained, alkali is added, the mixture is stirred at a certain temperature, so that the mixture A reacts, an organic solvent is added for extraction and liquid separation after the reaction ends, an organic phase is concentrated and dried, and daclatasvir is obtained. The method has the characteristics that the product produced with the method has high purity, the method is high in yield, low in cost and simple to operate and the process is stable.

Description

technical field [0001] The invention relates to the field of medicine and chemical industry, in particular to a method for preparing daclatasvir. Background technique [0002] Daclatasvir, the chemical name is ((1S)-1-(((2S)-2-(5-(4'-(2-((2S)-1-((2S)-2-((A Oxycarbonyl)amino)-3-methylbutyryl)-2-pyrrolidinyl)-1H-imidazol-5-yl)-4-biphenyl)-1H-imidazol-2-yl)-1-pyrrolidinyl Base) carbonyl) -2-methylpropyl) methyl carbamate, its structural formula is as follows: [0003] [0004] Daclatasvir belongs to an NS5A inhibitor and can be used for the treatment of chronic hepatitis C with compensatory liver disease including genotypes 1, 2, 3 and 4. The prior art shows that the yield of daclatasvir is not high, so the preparation process of daclatasvir needs to be further improved. Contents of the invention [0005] The present invention aims to solve one of the technical problems in the related art at least to a certain extent. For this reason, an object of the present invention...

Claims

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Application Information

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IPC IPC(8): C07D403/14
CPCC07D403/14
Inventor 陈辉林碧悦寇景平
Owner SUNSHINE LAKE PHARM CO LTD
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