CN107663168A - The synthetic method of pirfenidone - Google Patents
The synthetic method of pirfenidone Download PDFInfo
- Publication number
- CN107663168A CN107663168A CN201711189776.2A CN201711189776A CN107663168A CN 107663168 A CN107663168 A CN 107663168A CN 201711189776 A CN201711189776 A CN 201711189776A CN 107663168 A CN107663168 A CN 107663168A
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- CN
- China
- Prior art keywords
- pirfenidone
- synthetic method
- white crystal
- catalyst
- dosage
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
Abstract
The synthetic method of pirfenidone of the present invention is related to chemical field, and in particular to the synthetic method of pirfenidone, comprises the following steps：The aminopyridine 20g of 5 methyl 2,50% sulfuric acid solution 66mL are added in 500mL three-necked bottles, ice salt bath is cooled to less than 5 DEG C, the lower natrium nitrosum 34.5g for adding people to be dissolved in 50mL water of stirring, finish, continue stirring reaction ebuillition of heated after 3 hours under 0~5 degree, to stopping heating when being generated without gas, obtained settled solution natrium carbonicum calcinatum, is adjusted to neutrality, concentrate as, obtain brown solid, extracted, extract solution activated carbon decolorizing, be concentrated to dryness with 400mL methanol eddies, yellow solid is obtained, white crystal 16.2g is recrystallized to obtain with absolute ethyl alcohol；Present invention process is simple, and reaction safety, reaction temperature is low, and the dosage of reagent iodobenzene is few, and the dosage of catalyst is also greatly reduced, and more conforms to the actual demand of pharmaceutical production, has good industry prospect.
Description
Technical field
The present invention relates to chemical field, and in particular to the synthetic method of pirfenidone.
Background technology
Pirfenidone, the entitled 5- methyl isophthalic acids-phenyl -2 (1H)-of chemistry adjoin pyridine ketone, and this product has wide spectrum anti-fibrosis effect,
At present in the medicine listing of Japan and Europe as treatment pulmonary fibrosis.
The technique reported at present is to obtain 5- methyl -2 (1H)-pyridine through diazotising, hydrolysis with 2- amino -5- picolines
Ketone, then react with iodobenzene to obtain pirfenidone.This method is produced for 3 hours using the iodobenzene of excess as solvent in 1 80% reaction
Product.It is big to consume the iodobenzene amount of severe toxicity, reaction temperature is high, and two step yields are 50% or so.
The content of the invention
In order to solve the above problems, a kind of technique of present invention offer is simple, and reaction safety, reaction temperature is low, reagent iodobenzene
Dosage it is few, the dosage of catalyst is also greatly reduced, and more conforms to the actual demand of pharmaceutical production, has fine industry prospect
The synthetic method of pirfenidone.
The synthetic method of pirfenidone of the present invention, comprises the following steps：
The first step, 5- methyl-2-amino pyridines 20g, 50% sulfuric acid solution 66mL are added in 500mL three-necked bottles, ice salt bath
Less than 5 DEG C are cooled to, the lower natrium nitrosum 34.5g for adding people to be dissolved in 50mL water of stirring, finishes, it is anti-to continue stirring under 0~5 degree
Ebuillition of heated after answering 3 hours, to heating is stopped when being generated without gas, obtained settled solution natrium carbonicum calcinatum, neutrality is adjusted to,
Concentration as, obtain brown solid, with 400mL methanol eddies extract, extract solution activated carbon decolorizing, be concentrated to dryness, obtain yellow
Solid, white crystal 16.2g is recrystallized to obtain with absolute ethyl alcohol；
Second step, by the white crystal 10.9g obtained in the first step, Anhydrous potassium carbonate 16.51g, bromobenzene 18.84g, catalyst,
1,10- coffee sieve quinoline 0.5mmol and 50mL DMF reacts 2 hours at 90 DEG C, and display reaction is complete, cooling
To room temperature, add 200mL water and stir, filter, obtain white depositions, 5% acetic acid 150mL heating is added in sediment
To 90%, filtering, filtrate adjusts pH to 13 with 20% sodium hydroxide, and -10 DEG C of people's refrigerator is put after cooling overnight, there is white crystal analysis
Go out, mistake, filter, dry, obtain pirfenidone.
Preferably, catalyst is cuprous bromide.
Present invention process is simple, and reaction safety, reaction temperature is low, and the dosage of reagent iodobenzene is few, and the dosage of catalyst is also big
To reduce, the actual demand of pharmaceutical production is more conformed to, there is good industry prospect.
Embodiment
Embodiment one：
The synthetic method of pirfenidone of the present invention, comprises the following steps：
The first step, 5- methyl-2-amino pyridines 20g, 50% sulfuric acid solution 66mL are added in 500mL three-necked bottles, ice salt bath
Less than 5 DEG C are cooled to, the lower natrium nitrosum 34.5g for adding people to be dissolved in 50mL water of stirring, finishes, it is anti-to continue stirring under 0~5 degree
Ebuillition of heated after answering 3 hours, to heating is stopped when being generated without gas, obtained settled solution natrium carbonicum calcinatum, neutrality is adjusted to,
Concentration as, obtain brown solid, with 400mL methanol eddies extract, extract solution activated carbon decolorizing, be concentrated to dryness, obtain yellow
Solid, white crystal 16.2g is recrystallized to obtain with absolute ethyl alcohol；
Second step, by the white crystal 10.9g obtained in the first step, Anhydrous potassium carbonate 16.51g, bromobenzene 18.84g, catalyst,
1,10- coffee sieve quinoline 0.5mmol and 50mL DMF reacts 2 hours at 90 DEG C, and display reaction is complete, cooling
To room temperature, add 200mL water and stir, filter, obtain white depositions, 5% acetic acid 150mL heating is added in sediment
To 90%, filtering, filtrate adjusts pH to 13 with 20% sodium hydroxide, and -10 DEG C of people's refrigerator is put after cooling overnight, there is white crystal analysis
Go out, mistake, filter, dry, obtain pirfenidone.
Embodiment two：
The synthetic method of pirfenidone of the present invention, comprises the following steps：
The first step, 5- methyl-2-amino pyridines 20g, 50% sulfuric acid solution 66mL are added in 500mL three-necked bottles, ice salt bath
Less than 5 DEG C are cooled to, the lower natrium nitrosum 34.5g for adding people to be dissolved in 50mL water of stirring, finishes, it is anti-to continue stirring under 0~5 degree
Ebuillition of heated after answering 3 hours, to heating is stopped when being generated without gas, obtained settled solution natrium carbonicum calcinatum, neutrality is adjusted to,
Concentration as, obtain brown solid, with 400mL methanol eddies extract, extract solution activated carbon decolorizing, be concentrated to dryness, obtain yellow
Solid, white crystal 16.2g is recrystallized to obtain with absolute ethyl alcohol；
Second step, by the white crystal 10.9g obtained in the first step, Anhydrous potassium carbonate 16.51g, bromobenzene 18.84g, catalyst,
1,10- coffee sieve quinoline 0.5mmol and 50mL DMF reacts 2 hours at 90 DEG C, and display reaction is complete, cooling
To room temperature, add 200mL water and stir, filter, obtain white depositions, 5% acetic acid 150mL heating is added in sediment
To 90%, filtering, filtrate adjusts pH to 13 with 20% sodium hydroxide, and -10 DEG C of people's refrigerator is put after cooling overnight, there is white crystal analysis
Go out, mistake, filter, dry, obtain pirfenidone.Catalyst is cuprous bromide.Present invention process is simple, and reaction safety, reaction temperature is low,
The dosage of reagent iodobenzene is few, and the dosage of catalyst is also greatly reduced, and more conforms to the actual demand of pharmaceutical production, has good
Industry prospect.
Claims (2)
1. a kind of synthetic method of pirfenidone, it is characterised in that comprise the following steps：
The first step, 5- methyl-2-amino pyridines 20g, 50% sulfuric acid solution 66mL are added in 500mL three-necked bottles, ice salt bath
Less than 5 DEG C are cooled to, the lower natrium nitrosum 34.5g for adding people to be dissolved in 50mL water of stirring, finishes, it is anti-to continue stirring under 0~5 degree
Ebuillition of heated after answering 3 hours, to heating is stopped when being generated without gas, obtained settled solution natrium carbonicum calcinatum, neutrality is adjusted to,
Concentration as, obtain brown solid, with 400mL methanol eddies extract, extract solution activated carbon decolorizing, be concentrated to dryness, obtain yellow
Solid, white crystal 16.2g is recrystallized to obtain with absolute ethyl alcohol；
Second step, by the white crystal 10.9g obtained in the first step, Anhydrous potassium carbonate 16.51g, bromobenzene 18.84g, catalyst,
1,10- coffee sieve quinoline 0.5mmol and 50mL DMF reacts 2 hours at 90 DEG C, and display reaction is complete, cooling
To room temperature, add 200mL water and stir, filter, obtain white depositions, 5% acetic acid 150mL heating is added in sediment
To 90%, filtering, filtrate adjusts pH to 13 with 20% sodium hydroxide, and -10 DEG C of people's refrigerator is put after cooling overnight, there is white crystal analysis
Go out, mistake, filter, dry, obtain pirfenidone.
2. the synthetic method of pirfenidone as claimed in claim 1, it is characterised in that the catalyst is cuprous bromide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711189776.2A CN107663168A (en) | 2017-11-24 | 2017-11-24 | The synthetic method of pirfenidone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711189776.2A CN107663168A (en) | 2017-11-24 | 2017-11-24 | The synthetic method of pirfenidone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107663168A true CN107663168A (en) | 2018-02-06 |
Family
ID=61145189
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711189776.2A Withdrawn CN107663168A (en) | 2017-11-24 | 2017-11-24 | The synthetic method of pirfenidone |
Country Status (1)
| Country | Link |
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| CN (1) | CN107663168A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111039857A (en) * | 2019-12-25 | 2020-04-21 | 苏州雅尼生物科技有限公司 | Preparation method of high-purity pirfenidone |
-
2017
- 2017-11-24 CN CN201711189776.2A patent/CN107663168A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111039857A (en) * | 2019-12-25 | 2020-04-21 | 苏州雅尼生物科技有限公司 | Preparation method of high-purity pirfenidone |
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| Date | Code | Title | Description |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20180206 |