CN107513037A - A kind of preparation method of 1 substituted pyrazole derivative - Google Patents
A kind of preparation method of 1 substituted pyrazole derivative Download PDFInfo
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- CN107513037A CN107513037A CN201610428141.2A CN201610428141A CN107513037A CN 107513037 A CN107513037 A CN 107513037A CN 201610428141 A CN201610428141 A CN 201610428141A CN 107513037 A CN107513037 A CN 107513037A
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- prepare compound
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- 0 CCC(C=C1OC)=**1c1cccc(*)c1 Chemical compound CCC(C=C1OC)=**1c1cccc(*)c1 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
- C07D231/22—One oxygen atom attached in position 3 or 5 with aryl radicals attached to ring nitrogen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a kind of preparation method of the alcohol of 1 substituted pyrazole derivative 1 (3 aminophenyl) 3 ethyl 1H pyrazoles 5, using Propionylacetic acid ethyl ester as initiation material, target product is obtained by cyclization, condensation, reduction, the compound is important medicine intermediate.
Description
Technical field
The present invention relates to a kind of novel processing step of medicine intermediate, more particularly to a kind of 1- substituted pyrazole derivatives 1-
The preparation method of (3- aminophenyls) -3- ethyl -1H- pyrazoles -5- alcohol.
Technical background
Compound 1- (3- aminophenyls) -3- ethyl -1H- pyrazoles -5- alcohol, structural formula are：
This compound 1- (3- aminophenyls) -3- ethyl -1H- pyrazoles -5- alcohol and the derivative of correlation in pharmaceutical chemistry and
There is extensive use in organic synthesis.The synthesis of 1- (3- aminophenyls) -3- ethyl -1H- pyrazoles -5- alcohol is more difficult at present.
Therefore it is easy to get, it is necessary to develop a raw material, it is easy to operate, react easily controllable, the suitable synthetic method of overall yield.
The content of the invention
The invention discloses the method that one kind prepares 1- (3- aminophenyls) -3- ethyl -1H- pyrazoles -5- alcohol, with propionyl second
Acetoacetic ester is initiation material, obtains target product 4 by cyclization, condensation, reduction, synthesis step is as follows：
(1) using Propionylacetic acid ethyl ester as initiation material, 2 are obtained by ring closure reaction；
(2) condensation reaction is carried out 2, obtains 3；
(3) 3 progress tertbutyloxycarbonyl protection reactions are obtained 4；
In a preferred embodiment, the reagent used in described ring closure reaction prepare compound 2 is selected from hydrazine hydrate；Institute
The alkali used in condensation reaction prepare compound 3 stated is selected from potassium carbonate；Reduction used in described reduction reaction prepare compound 4
Agent is selected from lithium aluminium hydride.
In a preferred embodiment, the solvent used in described ring closure reaction prepare compound 2 is selected from toluene；It is described
Condensation reaction prepare compound 3 used in solvent be selected from N,N-dimethylformamide；Described reduction reaction prepare compound 4
Solvent used is selected from tetrahydrofuran.
In a preferred embodiment, the reaction temperature used in described ring closure reaction prepare compound 2 is solvent
Reflux temperature；Temperature used in described reduction reaction prepare compound 3 is the reflux temperature of solvent；Described reduction reaction system
Used in standby compound 4 is 0 DEG C~room temperature.
The present invention relates to a kind of preparation method of 1- (3- aminophenyls) -3- ethyl -1H- pyrazoles -5- alcohol, currently without it
He reports Patents documents.
The present invention is further described by the following embodiment, and these descriptions are not present invention to be made into one
The restriction of step.It should be understood by those skilled in the art that the equivalent substitution made to the technical characteristic of the present invention, or change accordingly
Enter, still fall within protection scope of the present invention.
Specific embodiment mode
Embodiment 1
(1) synthesis of 3- methylpyrazoles -5- alcohol
20g Propionylacetic acid ethyl esters are added in 130ml toluene, add 26g hydrazine hydrates, return stirring is overnight, and concentration is again
Add ethyl acetate and water, liquid separation, drying, concentration, the isolated 17g 3- methylpyrazoles -5- alcohol of residue upper prop.
(2) synthesis of 3- methyl isophthalic acids-(3- nitrobenzophenones) -1H- pyrazoles -5- alcohol
16g 3- methylpyrazole -5- alcohol is added in 250ml DMFs, adds 9g Carbon Dioxides
Potassium and 24g3- Nitrobromobenzenes, stirring 2 hours is heated to reflux, is cooled to room temperature, be slowly added to ethyl acetate and water, extraction point
Liquid, drying, concentration, silica gel post separation obtains 19g 3- methyl isophthalic acids-(3- nitrobenzophenones) -1H- pyrazoles -5- alcohol on residue.
(3) synthesis of 1- (3- aminophenyls) -3- ethyl -1H- pyrazoles -5- alcohol
18g 3- methyl isophthalic acids-(3- nitrobenzophenones) -1H- pyrazoles -5- alcohol is added in 200ml anhydrous tetrahydro furans, it is cold
But 0 DEG C, then 6g Lithium Aluminium Hydrides are slowly added portionwise, it is stirred at room temperature 6 hours, adds sodium hydrate aqueous solution, filtering, collect female
Liquid, ethyl acetate is added, extract liquid separation, dried, concentration, silica gel post separation obtains 9g 1- (3- aminophenyls) -3- second on residue
Base -1H- pyrazoles -5- alcohol.
Claims (5)
1. the method that one kind prepares 1- substituted pyrazole derivatives 1- (3- aminophenyls) -3- ethyl -1H- pyrazoles -5- alcohol, with propionyl
Ethyl acetate is initiation material, and target product 4 is obtained by cyclization, condensation, reduction, and synthetic route is as follows,
2. method according to claim 1, it is characterised in that the reagent used in described ring closure reaction prepare compound 2 is selected from
Hydrazine hydrate；Alkali used in described condensation reaction prepare compound 3 is selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, carbonic acid
One or more of mixtures in sodium, potassium carbonate, triethylamine, sodium acid carbonate, pyridine, triisopropylamine, saleratus；It is described
Reduction reaction prepare compound 4 used in reducing agent be selected from sodium borohydride, potassium borohydride, lithium borohydride, sodium cyanoborohydride,
One or more of mixtures in lithium aluminium hydride, borine.
3. method according to claim 1, it is characterised in that the solvent used in described ring closure reaction prepare compound 2 is selected from
Methanol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene, meta-xylene, N,
One or more of mixtures in dinethylformamide, DMAC N,N' dimethyl acetamide；Described condensation reaction prepares chemical combination
Solvent used in thing 3 be selected from methanol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dichloromethane, toluene, ortho-xylene, to two
One or more of mixtures in toluene, meta-xylene, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, water；It is described
Reduction reaction prepare compound 4 used in solvent be selected from methanol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dichloromethane,
One kind or several in toluene, ortho-xylene, paraxylene, meta-xylene, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide
The mixture of kind.
4. method according to claim 1, it is characterised in that the reaction temperature used in described ring closure reaction prepare compound 2
It is the reflux temperature of 0 DEG C~solvent；Temperature used in described reduction reaction prepare compound 3 is the backflow temperature of 0 DEG C~solvent
Degree；Used in described reduction reaction prepare compound 4 is 0 DEG C~room temperature.
5. method according to claim 1, it is characterised in that the reaction temperature used in described ring closure reaction prepare compound 2
It is the reflux temperature of solvent；Temperature used in described reduction reaction prepare compound 3 is the reflux temperature of solvent；Described goes back
Used in original reaction prepare compound 4 is 0 DEG C~room temperature.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610428141.2A CN107513037A (en) | 2016-06-16 | 2016-06-16 | A kind of preparation method of 1 substituted pyrazole derivative |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610428141.2A CN107513037A (en) | 2016-06-16 | 2016-06-16 | A kind of preparation method of 1 substituted pyrazole derivative |
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| Publication Number | Publication Date |
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| CN107513037A true CN107513037A (en) | 2017-12-26 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201610428141.2A Withdrawn CN107513037A (en) | 2016-06-16 | 2016-06-16 | A kind of preparation method of 1 substituted pyrazole derivative |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104262257A (en) * | 2014-10-12 | 2015-01-07 | 湖南华腾制药有限公司 | Preparation method of pyrazole derivative |
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2016
- 2016-06-16 CN CN201610428141.2A patent/CN107513037A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104262257A (en) * | 2014-10-12 | 2015-01-07 | 湖南华腾制药有限公司 | Preparation method of pyrazole derivative |
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Application publication date: 20171226 |
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| WW01 | Invention patent application withdrawn after publication |