Method for producing phenoxypyridine derivative

A technology of piperidine and methyl, which is applied in the directions of medical preparations, drug combinations, and pharmaceutical formulations containing active ingredients, can solve the problems such as preparation of intermediates that are not disclosed.

Inactive Publication Date: 2009-06-10
EISIA R&D MANAGEMENT CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] However, Patent Document 1 discloses a compound similar in structure to the present compound and its preparation method, but the pr

Method used

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  • Method for producing phenoxypyridine derivative
  • Method for producing phenoxypyridine derivative
  • Method for producing phenoxypyridine derivative

Examples

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preparation example Construction

[0148] The preparation method of the present invention is described in detail below.

[0149]

[0150] [In the formula, each symbol has the same meaning as defined above. 〕

[0151] [step 1]

[0152] This step is a step of preparing compound (VIII) by reacting compound (IX) and compound (X) in the presence of a halogenating agent or a condensing agent.

[0153] As the compound (IX), there can be used compounds described in the following Examples, known compounds, commercially available compounds, or compounds that can be easily prepared from commercially available compounds by methods generally performed by those skilled in the art.

[0154] As the compound (X), there can be used compounds described in the following Examples, known compounds, commercially available compounds, or compounds that can be easily prepared from commercially available compounds by methods generally performed by those skilled in the art.

[0155] The solvent used in this step is not particularly ...

preparation example 1

[0222] (Preparation Example 1) [1-(2-Dimethylaminoacetyl)piperidin-4-yl]amino tert-butyl formate

[0223]

[0224] Add N,N-dimethylglycine (2.97g), 1-hydroxybenzene Triazole (3.89g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (5.27g) were stirred at room temperature for 46 hours under a nitrogen atmosphere. Ethyl acetate (400 ml), saturated brine (200 ml), and 1N aqueous sodium hydroxide solution (50 ml) were added to the reaction solution, stirred at room temperature for 30 minutes, and then partitioned. The aqueous layer was extracted with ethyl acetate. The organic layer was collected, washed successively with 1N aqueous sodium hydroxide solution and saturated brine, and dried over anhydrous sodium sulfate. The dried organic layer was concentrated under reduced pressure to obtain the title compound (8.03 g, quantitative) as colorless crystals.

[0225] ESI-MS(m / z): 286[M+H] + .

preparation example 2

[0226] (Preparation Example 2) N-[1-(2-Dimethylaminoethyl)piperidin-4-yl] -N-Methylamine

[0227]

[0228] A solution of tert-butyl [1-(2-dimethylaminoacetyl)piperidin-4-yl]carbamate (7.07 g) in tetrahydrofuran (100 ml) was stirred with ice-cooling under a nitrogen atmosphere. Lithium aluminum hydride (280 mg) was added thereto, followed by stirring on an ice bath for 15 minutes and at room temperature for 15 minutes. Under a nitrogen atmosphere, the reaction solution was heated to reflux at 100° C. for 11 hours. Ice cold reaction solution. Water (2.8 ml), 5N aqueous sodium hydroxide solution (2.8 ml), and water (14.0 ml) were successively added thereto, and it was stirred for 2 hours. Insolubles were filtered. The filtrate was concentrated to give the title compound (4.65 g, quantitative) as a yellow oil.

[0229] 1 H-NMR spectrum (CDCl 3 )δ (ppm): 1.34-1.43 (2H, m), 1.87-1.90 (2H, m), 2.02-2.08 (2H, m), 2.25 (6H, s), 2.31-2.50 (7H, m), 2.90 (2H, m), 3.14-3.27 (...

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Abstract

A process for preparing a compound represented by the formula (I): comprising reacting a compound represented by the formula (II) or salt thereof: with a compound represented by the formula (III): in the presence of a condensation reagent, wherein R 1 represents 1) optionally substituted azetidin-1-yl, 2) optionally substituted pyrrolidin-1-yl, 3) optionally substituted piperidin-1-yl, etc, R2, R3, R4 and R5 may be the same or different and each represents hydrogen or fluorine; and R6 represents hydrogen or fluorine.

Description

technical field [0001] The present invention relates to an antitumor agent, a cancer metastasis inhibitor, etc., which have hepatocyte growth factor receptor (Hepatocyte growth factor receptor; hereinafter abbreviated as "HGFR") inhibitory action, antitumor action, angiogenesis inhibitory action, cancer metastasis inhibitory action, etc. A method for producing a phenoxypyridine derivative useful as an agent (hereinafter referred to as "the present compound") and a production intermediate of the production method. Background technique [0002] It has been reported that HGFR is overexpressed in various tumors such as pancreatic cancer, gastric cancer, colorectal cancer, breast cancer, prostate cancer, lung cancer, kidney cancer, brain tumor, and ovarian cancer (Non-Patent Document 1). It is considered that HGFR expressed in the above tumor cells is constantly or stimulated by hepatocyte growth factor (hepatocyte growth factor; hereinafter referred to as "HGF"), which causes au...

Claims

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Application Information

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IPC IPC(8): C07D213/73C07D213/75C07D213/81C07D401/12A61K31/4427A61K31/4439A61K31/4545A61K31/496A61P9/00A61P35/00A61P35/04A61P43/00
CPCC07D213/73C07D213/75C07D213/81C07D401/12A61P35/00A61P35/04A61P43/00A61P9/00
Inventor 永井光雄松岛知广镰田厚若杉和纪白鸟修司阿部信也奈良一诚坂口贵久
Owner EISIA R&D MANAGEMENT CO LTD
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