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Method for preparing fosamprenavir intermediate

A technology of fusarnavir and intermediates, applied in the field of heterocyclic chemistry, can solve the problems of low activity of tetrahydrofuran-3-chloroformate, low yield of active esters, expensive active reagents, etc., and achieve simple reaction types , easy operation, high industrial application and economic value

Active Publication Date: 2012-07-18
ZHEJIANG JIUZHOU PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0025] The purpose of the present invention is to overcome in above-mentioned prior art, and transesterification reaction yield is low, and (S)-tetrahydrofuran-3-chloroformate activity is low, and used N, N '-disuccinimidyl carbonate The active reagent is expensive, and the disadvantages such as the low yield of active ester provide a new preparation method of fusarnavir intermediate

Method used

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  • Method for preparing fosamprenavir intermediate
  • Method for preparing fosamprenavir intermediate
  • Method for preparing fosamprenavir intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Embodiment 1: the preparation of formula 4-1 compound

[0059]

[0060] (S)-tetrahydrofuran-3-ol (3.52g, 0.04mol) and triethylamine (5.05g, 0.05mol) were mixed and dissolved in 30ml of dichloromethane, and methyl chloroformate (4.25g, 0.045mol) was added dropwise to In the reactor, after the dropwise addition is completed, the reaction is continued at 30-50° C. for 3-10 hours. TLC detects that the raw material disappears, and a quantitative crude compound of formula 4-1 is obtained.

Embodiment 2

[0061] Embodiment 2: the preparation of formula 4-2 compound

[0062]

[0063] According to the method of Example 1, phenyl chloroformate (6.24g, 0.04mol) and sodium carbonate (8.48g, 0.08mol) were operated in the same way to obtain a quantitative compound of formula 4-2.

Embodiment 3

[0064] Embodiment 3: the preparation of formula 4-3 compound

[0065]

[0066] According to the method of Example 1, benzyl chloroformate (6.8 g, 0.04 mol) and pyridine (4.74 g, 0.06 mol) were operated in the same way to obtain a quantitative compound of formula 4-2.

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Abstract

The invention relates to the technical field of heterocyclic chemistry, in particular to the technical field of heterocyclic chemistry which contains an oxygen atom that is taken as the only heterocyclic atom. The invention specifically discloses a method for preparing a fosamprenavir intermediate. The method for preparing the fosamprenavir intermediate comprises the steps: (S)-terahydrofuran-3-alcohol is taken as a raw material to react with chloro-carbonic ester under the alkaline condition, the obtained compound in an active ester formula (4) can directly react with the compound in the following formula (7) to prepare the compound in the following formula (8), and the compound in the formula (8) is used as a key intermediate for preparing the fosamprenavir. Catalyst can also be added when the compound in the formula (4) is used for preparing the compound in the formula (8), so the reaction yield is improved. Meanwhile, all the intermediate compounds which are obtained from the reaction of all the steps during the preparation process of the compound in the formula (8) can be free from separation from each other and directly enter the subsequent reaction, i.e. one-pot reaction can be carried out, wherein R1 is alkyl or aryl.

Description

technical field [0001] The present invention relates to the technical field of heterocyclic chemistry, in particular to the technical field of heterocyclic chemistry containing an oxygen atom as the only heterocyclic atom. Background technique [0002] The compound of formula 8 is 1S-benzyl-2R-hydroxyl-3-[isobutyl-(4-nitrobenzenesulfonyl)amino]propyl-carbamic acid tetrahydrofuran-3Syl ester, CAS number is 160231-69-6 , the structural formula is as follows: [0003] [0004] It is the key intermediate of synthetic Fusamprenavir (Fosamprenavir): [0005] [0006] The trade name of Fusarnavir is Lexiva, which is a high-efficiency protease inhibitor (PI) for the treatment of AIDS jointly developed by GSK of the United Kingdom and Vertex of the United States. Fusarnavir is a highly water-soluble low-activity phosphate ester, which is convenient to use and has a good development prospect. The drug was officially approved by the FDA on June 14, 2007 to be marketed in the U...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/20
Inventor 姚庆旦高红军车大庆
Owner ZHEJIANG JIUZHOU PHARM CO LTD
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