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Synthesis technology for ledipasvir intermediate

A synthesis process and intermediate technology, which is applied in the field of synthesis process of ledipasvir intermediates, can solve problems such as unfavorable reactions and reduced synthesis yield of ledipasvir, and achieve the goals of reducing impurity content, facilitating promotion and reducing costs Effect

Pending Publication Date: 2018-11-06
慎终(上海)生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, in the conventional synthesis of ledipasvir intermediates, more impurities are produced, which leads to a decrease in the yield of ledipasvir synthesis and is not conducive to the subsequent reactions

Method used

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  • Synthesis technology for ledipasvir intermediate

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0013] The synthetic technique of this ledipasvir intermediate comprises the following steps:

[0014] The first step is raw material selection, and methyl glyoxylate is selected as the raw material for the synthesis of ledipasvir intermediate;

[0015] In the second step, the synthesis of ledipasvir intermediate, add 22g of methyl glyoxylate in a four-neck flask with a thermometer, agitator, and reflux condenser, and then add 12g of R(+)-α- Methylbenzylamine, 200mL of acetic acid, then heated to 58 ° C for 1.5h to obtain a Schiff base compound after the reaction, and then add the Schiff base compound in a four-necked flask with a thermometer, a stirrer, and a reflux condenser, Then add 30mL of cyclopentadiene, 220mL of DMF solvent, 18g of cellulase, and 12g of pectinase, then react at 42°C for 1.2h, and then purify to obtain the intermediate of ledipasvir .

Embodiment 2

[0017] The synthetic technique of this ledipasvir intermediate comprises the following steps:

[0018] The first step is raw material selection, and methyl glyoxylate is selected as the raw material for the synthesis of ledipasvir intermediate;

[0019] In the second step, the synthesis of ledipasvir intermediate, add 24g of methyl glyoxylate in a four-necked flask with a thermometer, agitator, and reflux condenser, and then add 13g of R(+)-α- Methylbenzylamine, 210mL of acetic acid, then heated to 58 ° C for 2h to obtain a Schiff base compound after the reaction, then add the Schiff base compound in a four-necked flask with a thermometer, a stirrer, and a reflux condenser, and then Add 30mL of cyclopentadiene, 220mL of DMF solvent, 18g of cellulase, and 12g of pectinase, and then react at 42°C for 1.6h, and then purify to obtain the intermediate of ledipasvir.

Embodiment 3

[0021] The synthetic technique of this ledipasvir intermediate comprises the following steps:

[0022] The first step is raw material selection, and methyl glyoxylate is selected as the raw material for the synthesis of ledipasvir intermediate;

[0023] In the second step, the synthesis of ledipasvir intermediate, add 28g of methyl glyoxylate in a four-necked flask with a thermometer, agitator, and reflux condenser, and then add 14g of R(+)-α- Methylbenzylamine, 220mL of acetic acid, then heated to 58 ° C for 2.5h to obtain a Schiff base compound after the reaction, then add the Schiff base compound in a four-necked flask with a thermometer, a stirrer, and a reflux condenser, Then add 30mL of cyclopentadiene, 220mL of DMF solvent, 18g of cellulase, 12g of pectinase, and then react at 42°C for 1.8h, and then purify to obtain the intermediate of ledipasvir .

[0024] The intermediates of ledipasvir synthesized in Example 1, Example 2, and Example 3 of the present invention wer...

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Abstract

The invention discloses a synthesis technology for a ledipasvir intermediate. The synthesis technology is carried out through the steps of raw material selection and ledipasvir intermediate synthesis.The synthesis technology has the beneficial effects that synthesis steps are simple, impurity contents generated during the ledipasvir intermediate synthesis can be reduced so as to bring conveniencefor subsequent reaction, the synthesis efficiency of a ledipasvir finished product is improved, the yield of ledipasvir is improved, and therefore, the synthesis technology is favorable for realizingmass production and is also favorable for promotion, has a good use effect, and cost is lowered.

Description

technical field [0001] The invention relates to the technical field of synthesis of ledipasvir, in particular to a synthesis process of a ledipasvir intermediate. Background technique [0002] Ledipasvir (ledipasvir), chemical name: N-[(2S)-1-[(6S)-6-[5-[9,9-difluoro-7-[2-[(1S,2S,4R )-3-[(2S)-2-(Methoxycarbonylamino)-3-methylbutyryl]-3-azabicyclo[2.2.1]-2-heptyl]-3H-benzimidazole- 5-yl]-2-fluorenyl]-1H-2-imidazolyl]-5-azaspirane[2.4]-5-heptyl]-3-methyl-1-oxo-2-butyl]amino Methyl formate, was developed by Gilead Sciences. [0003] At present, in the conventional synthesis of ledipasvir intermediates, there are more impurities produced, which leads to a decrease in the yield of ledipasvir synthesis and is not conducive to the subsequent reactions. Contents of the invention [0004] The present invention aims to solve the problems existing in the above-mentioned prior art, and provides a synthesis process of a ledipasvir intermediate, which reduces impurities generated dur...

Claims

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Application Information

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IPC IPC(8): C12P17/16
CPCC12P17/165
Inventor 刘如成张军王爱荣
Owner 慎终(上海)生物科技有限公司
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