Synthetic method of 4-fluoroisoquinoline-5-amine

A technique for the synthesis of fluoroisoquinoline, which is applied in organic chemistry and other fields, can solve the problems of lack of suppliers and high price of 4-fluoroisoquinoline, and achieve simple and easy-to-obtain raw materials, convenient operation and post-treatment, and process selection reasonable effect

Inactive Publication Date: 2018-09-21
SUZHOU KANGRUN PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the raw material 4-fluoroisoquinoline is ...

Method used

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  • Synthetic method of 4-fluoroisoquinoline-5-amine

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Embodiment

[0049] The first step: the synthesis of 4-fluoro-3-methoxyisoquinolin-1-ol

[0050] Add isoquinolin-1-ol (14.5g, 0.1mol) to MeCN (100ml), MeOH (100ml), Selectfluor (1.3eq), and then heat up and reflux for 3h. Vote for the next step.

[0051] The second step: the synthesis of 4-fluoroisoquinolin-1-ol

[0052] 4-fluoro-3-methoxyisoquinolin-1-ol (0.1mol) was dissolved in 0.5NHCl.aq (100ml), EA (100ml), stirred overnight at 40°C, extracted with EA, and the product was obtained by column chromatography ( 13 g, 80%).

[0053] The third step: the synthesis of 1-chloro-4-fluoroisoquinoline

[0054] 4-Fluoroisoquinolin-1-ol (33g, 0.2mol) was added to POCl3 (150ml) in batches, and the temperature was raised to reflux for 3h. After the reaction was completed, the excess POCl 3 , Na 2 CO 3 aq. Adjust the pH, extract with EA and spin dry column chromatography to obtain the product (25 g, 70%).

[0055] The fourth step: the synthesis of 4-fluoroisoquinoline

[0056] 1-Chloro-4-fluor...

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Abstract

The invention provides a synthetic method of 4-fluoroisoquinoline-5-amine. The synthetic method comprises the following steps: taking isoquinoline-1-ol as a raw material and reacting the isoquinoline-1-ol with Selectfluor to obtain 4-fluoro-3-methoxylisoquinoline-1-ol; dissolving the 4-fluoro-3-methoxylisoquinoline-1-ol in HCl and reacting to obtain 4-fluoroisoquinoline-1-ol and reacting the 4-fluoroisoquinoline-1-ol with phosphorus oxychloride to obtain 1-chloro-4-fluoroisoquinoline; obtaining 4-fluoroisoquinoline under the catalysis of a catalyst; reacting the 4-fluoroisoquinoline with concentrated nitric acid to obtain 4-fluoro-5-nitroisoquinoline; finally, under the acid condition, carrying out iron powder reduction to obtain the 4-fluoroisoquinoline-5-amine. The synthetic method of the 4-fluoroisoquinoline-5-amine, disclosed by the invention, has the advantages of concise route, reasonable technology, low cost of raw materials, simplicity and easiness in obtaining, convenience inoperation and post treatment, high total yield, no use of a poisonous reagent, easiness in enlargement and capability of producing the 4-fluoroisoquinoline-5-amine on a large scale.

Description

technical field [0001] The invention belongs to the technical field of synthesis of isoquinoline compounds, and relates to a synthesis method of 4-fluoroisoquinolin-5-amine. Background technique [0002] Isoquinoline compounds are a very important class of azacyclic alkaloids, which have remarkable physiological activities and broad application prospects. Studies have found that isoquinoline alkaloids can exert anti-tumor effects through different mechanisms such as alkylation, receptor regulation, inhibition of anti-apoptotic genes, and inhibition of angiogenesis. At present, isoquinoline has played a huge role in drugs, such as anesthetics (dimethylisoquinoline), antihypertensive drugs (quinapril hydrochloride), antifungal drugs (1,2,3,4- Hydroquinazoline), vasodilators (papaverine), etc. At the same time, isoquinoline compounds can also be used in the manufacture of dyes, paints, pesticides, preservatives and disinfectants. In the process of drug design, fluorine atoms...

Claims

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Application Information

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IPC IPC(8): C07D217/22
CPCC07D217/22
Inventor 赵啸颖徐卫良徐炜政
Owner SUZHOU KANGRUN PHARMA
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