Method for producing 4-oxoquinoline compound

A compound and representative technology, applied in the field of preparation of anti-HIV drugs, can solve problems such as not providing compound descriptions

Active Publication Date: 2009-05-20
JAPAN TOBACCO INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it does not provide a description of the compound (2') of the present invention detailed below

Method used

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  • Method for producing 4-oxoquinoline compound
  • Method for producing 4-oxoquinoline compound
  • Method for producing 4-oxoquinoline compound

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[1095] One example of the production method of the present invention is explained below. However, the present invention is not limited thereto.

[1096] 【0443】

[1097] Even if there is no description of the preparation method, those of ordinary skill in the art can understand that effective preparation can be carried out by introducing protective groups into functional groups, removing protective groups during post-treatment, converting to desired functional groups at any stage, etc. as appropriate.

[1098] 【0444】

[1099] Post-treatment after the reaction of each step can be applied by a typical method in which isolation and purification are performed by selecting as appropriate or combining various conventional methods such as crystallization, recrystallization, distillation, partition, silica gel column chromatography, preparative HPLC, and the like.

[1100] In the following preparation methods and this specification, unless otherwise specified, "room temperature" gene...

Embodiment 1

[1682] step 1

[1683] Synthesis of 5-bromo-2,4-dimethoxybenzoic acid

[1684] 【0619】

[1685]

[1686] 【0620】

[1687] 2,4-Dimethoxybenzoic acid (30.0 g) was suspended in acetic acid (180 ml). A bromine (27.6 g) / acetic acid (60 ml) solution was slowly added dropwise to the suspension. After the dropwise addition, the mixture was stirred at 25° C. for 2 hours, and the reaction was confirmed to be terminated by HPLC. An aqueous solution of sodium sulfite (2.10 g) and water (360 ml) was added dropwise to the reaction mixture. After the dropwise addition was complete, the mixture was stirred at 25° C. for 1 hour. The precipitated crystals were filtered, washed with water (150ml) 4 times, and dried in vacuo to give 5-bromo-2,4-dimethoxybenzoic acid as white crystals (41.2g) (96%).

[1688] 【0621】

[1689] step 2

[1690] Synthesis of methyl 5-bromo-2,4-dimethoxybenzoate

[1691] 【0622】

[1692]

[1693] 【0623】

[1694] 5-Bromo-2,4-dimethoxybenzoic acid (10.0 g) and...

Embodiment 2

[1815] step 1

[1816] Synthesis of 3-chloro-2-fluorobenzylzinc bromide

[1817] 【0665】

[1818]

[1819] 【0666】

[1820] Under an argon atmosphere, suspend zinc powder (3.18g) in tetrahydrofuran (8ml), and add 1,2-dibromoethane (0.061g, 0.32mol) and trimethylsilyl chloride in sequence at 60°C (0.071 g, 0.65 mol), the mixture was stirred for 30 min. A solution of 3-chloro-2-fluorobenzyl bromide (7.48 g, 32.5 mol) in tetrahydrofuran (20 ml) was added dropwise to the above prepared solution at 60°C. With heating, the mixture was further stirred for 1 hour to obtain a solution of 3-chloro-2-fluorobenzylzinc bromide in tetrahydrofuran.

[1821] Step II

[1822] Synthesis of methyl 5-bromo-2-fluoro-4-methoxybenzoate

[1823] 【0667】

[1824]

[1825] 【0668】

[1826] With stirring under ice-cooling, concentrated sulfuric acid (14 ml) was added dropwise to methanol (840 ml). Then, 2-fluoro-4-methoxybenzoic acid (70.0 g) was added, and the mixture was stirred at 65° C. f...

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PUM

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Abstract

The present invention provides a compound useful as a synthetic intermediate for an anti-HIV agent having an integrase inhibitory activity, and a production method thereof, and a production method of an anti-HIV agent using the synthetic intermediate. Specifically, for example, a compound represented by the formula (2'): wherein R is a fluorine atom or a methoxy group, and R<400> is a hydrogen atomor a C1-C4 alkyl group, or a salt thereof, and a production method thereof, and a production method of an anti-HIV agent using the synthetic intermediate.

Description

[0001] invention technical field [0002] 【0001】 [0003] The present invention relates to compounds that can be used as synthetic intermediates of anti-HIV drugs having integrase inhibitory activity and their preparation methods. In addition, the present invention also relates to a preparation method of an anti-HIV drug, which uses the synthetic intermediate and the like. Background of the invention [0004] 【0002】 [0005] Patent Reference 1 discloses a process for preparing 4-oxoquinoline compounds represented by formula [III] [0006] 【0003】 [0007] [0008] 【0004】 [0009] wherein each symbol is the same as described in Patent Reference 1 (hereinafter sometimes abbreviated as compound [III]), especially, the following production methods are known. [0010] 【0005】 [0011] Production method 1-1 (see patent reference 1: page 67) [0012] 【0006】 [0013] [0014] 【0007】 [0015] Each symbol in this process is the same as that described in Patent Reference 1. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C65/24C07C51/353C07C67/32C07C67/343C07C69/738C07C69/92C07C69/94C07C229/34C07D215/56
Inventor 松田浩二安藤公司大木繁治星淳一山崎隆博
Owner JAPAN TOBACCO INC
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