Preparation method for hydronidone

A hydroxyl and compound technology, which is applied in the field of medicine, can solve the problems of increasing the reaction process, cumbersome operation, and low yield

Inactive Publication Date: 2018-02-16
BEIJING CONTINENT PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] A kind of synthetic method of formula I compound is disclosed in the prior art, with 2-amino-5 picoline as starting raw material, this method uses Me as phenolic hydroxyl protecting group, and the used reagent price of its deprotection is expensive, and reaction process It is easy to form highly toxic gas in the medium, and the sewage waste treatment is cumbersome, the operation is cumbersome, and the yield is low (40%)
Moreover, most of the methods for preparing oxynidone in the prior art involve the protection of the hydroxyl group of p-bromophenol, and the industrial process needs to increase the complicated reaction process.

Method used

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  • Preparation method for hydronidone

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Experimental program
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preparation example Construction

[0039] (4) The preparation method of the present invention is simple and easy to operate, has mild reaction conditions, short reaction time, high yield, is safer and is suitable for large-scale production.

[0040] raw material

[0041] The raw material list that the present invention adopts is as shown in table 1 below:

[0042] Material name

Embodiment 1

[0045] Embodiment 1-production route 1:

[0046] 1. Formula II compound: the synthesis of N-(4-methoxyphenyl)-5-methyl-2-pyridone

[0047]

[0048]

[0049] The above-mentioned raw material feeding amount and feeding ratio are shown in Table 2:

[0050] Table 2

[0051] Material name

molar ratio

Molar weight (mol)

Feeding amount (kg)

2-Hydroxy-5-methylpyridine

1.00

390

35.0

p-Bromoanisole

1.20

468

74.0

Cuprous iodide

0.02

7.8

1.22

Anhydrous Potassium Carbonate

1.20

468

65.0

DMAC

-

-

190.0

[0052] (1) DMAC (190kg, concentration is 99wt%) is heated to 50 ℃, adds 2-hydroxyl-5-picoline 35kg, anhydrous potassium carbonate 65kg, p-bromoanisole 74.0kg and cuprous iodide 1.22 kg, heat up to reflux, react for 12-14h, and stop heating after using a spot plate (TCL) to control to the point where there is no raw material. Then the liquid temperature was lowered to 80°C and f...

Embodiment 2

[0064] Embodiment 2-production route 2

[0065] 1. Formula II compound: the synthesis of N-(4-methoxyphenyl)-5-methyl-2-pyridone

[0066]

[0067] The above-mentioned raw material feeding amount and feeding ratio are shown in Table 3:

[0068] table 3

[0069] Material name

molar ratio

Molar weight (mol)

Feeding amount (kg)

2-Hydroxy-5-methylpyridine

1.00

367

40.0

p-Bromoanisole

1.10

403.7

75.0

Copper Sulfate Pentahydrate

0.12

43.26

10.8

Anhydrous Potassium Carbonate

2.13

781.42

108.0

DMF

-

-

230.0

[0070] (1) As shown in Table 2, add p-bromoanisole, DMF, 2-hydroxy-5-picoline, anhydrous potassium carbonate and copper sulfate pentahydrate in sequence, heat up to reflux, react for 12-14h, and use point After the plate (TCL) is controlled to no raw material point, stop heating.

[0071] (2) The above-mentioned mixed solution is cooled to room temperature and filtered, ...

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Abstract

The invention provides a preparation method for hydronidone. The preparation method has the advantages of simple and convenient operation, mild reaction conditions, short reaction time, high yield, more safety, and applicability to mass production. The preparation method provided by the invention adopts ammonia water for treatment of a crude intermediate compound product, thereby facilitating removal of residual copper ions in a catalyst and extraction of a product.

Description

technical field [0001] The invention belongs to the field of medicine, in particular, the invention relates to copper-catalyzed carbon-heterocoupling reaction and its application, in particular to a preparation method of oxynidone. Background technique [0002] Liver fibrosis is the common pathological basis in the progress of chronic liver diseases. Various chronic injuries cause liver cell degeneration and necrosis, abnormal proliferation and excessive deposition of fibrous connective tissue, wrapping regenerated liver cells, forming "pseudolobules" and destroying the original liver tissue In the end, the liver will become nodular and harden, and the liver function will be damaged or even disappear completely, forming cirrhosis. [0003] A variety of chronic diseases can cause liver fibrosis, such as chronic viral hepatitis, chronic alcoholism, cholestasis, metabolic disorders caused by congenital enzyme defects, long-term exposure to poisons and drugs, etc. Liver fibrosi...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): C07D213/64
CPCC07D213/64
Inventor罗楹
OwnerBEIJING CONTINENT PHARM CO LTD