CN107400127A - A kind of preparation method of fluorine-containing imidazopyridine derivatives - Google Patents
A kind of preparation method of fluorine-containing imidazopyridine derivatives Download PDFInfo
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- CN107400127A CN107400127A CN201610341530.1A CN201610341530A CN107400127A CN 107400127 A CN107400127 A CN 107400127A CN 201610341530 A CN201610341530 A CN 201610341530A CN 107400127 A CN107400127 A CN 107400127A
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- prepare compound
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- xylene
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- JSAPJXGLIRVDFJ-UHFFFAOYSA-N CCOC(c1c[n](ccc(F)c2)c2n1)=O Chemical compound CCOC(c1c[n](ccc(F)c2)c2n1)=O JSAPJXGLIRVDFJ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
The invention discloses a kind of fluorine-containing flumizole of imidazopyridine derivatives 2 (chloromethyl) 7 simultaneously [1,2 a] pyridine preparation method, using the fluorine pyridine of 2 amino 4 as initiation material, target product is obtained by cyclization, reduction, chlorination, 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 fluorine-containing imidazopyridine derivatives
The preparation method of 2- (chloromethyl) -7- fluoro- imidazo [1,2-a] pyridine.
Technical background
Compound 2- (chloromethyl) -7- fluoro- imidazo [1,2-a] pyridine, structural formula are：
The fluoro- imidazos of this compound 2- (chloromethyl) -7- [1,2-a] pyridine and the derivative of correlation are in pharmaceutical chemistry and organic synthesis
With extensive use.The synthesis of 2- (chloromethyl) -7- fluoro- imidazo [1,2-a] pyridine is more difficult at present.Therefore, it is necessary to develop one
Individual raw material is easy to get, easy to operate, reacts easily controllable, the suitable synthetic method of overall yield.
The content of the invention
The invention discloses the method that one kind prepares 2- (chloromethyl) -7- fluoro- imidazo [1,2-a] pyridine, 2- amino -4- fluorine pyridines are
Beginning raw material, target product 4 is obtained by cyclization, reduction, chlorination, synthesis step is as follows：
(1) using 2- amino -4- fluorine pyridines as initiation material, 2 are obtained by ring closure reaction；
(2) reduction reaction is carried out 2, obtains 3；
(3) 3 progress chlorination reactions are obtained 4；
In a preferred embodiment, the reagent used in described ring closure reaction prepare compound 2 is selected from 3-BrPA second
Ester；Reducing agent used in described reduction reaction prepare compound 3 is selected from sodium borohydride；Described chlorination reaction prepare compound
Chlorinating agent used in 4 is selected from thionyl chloride.
In a preferred embodiment, the solvent used in described ring closure reaction prepare compound 2 is selected from glycol dimethyl ether；
Solvent used in described reduction reaction prepare compound 3 is selected from methanol；It is molten used in described chlorination reaction prepare compound 4
Agent is selected from toluene.
In a preferred embodiment, the reaction temperature used in described ring closure reaction prepare compound 2 is the room temperature of solvent；
Temperature used in described reduction reaction prepare compound 3 is room temperature；Used in described chlorination reaction prepare compound 4 is molten
The reflux temperature of agent.
The present invention relates to the preparation method of a kind of 2- (chloromethyl) -7- fluoro- imidazo [1,2-a] pyridine, currently without other Patents
Document report.
The present invention is further described by the following embodiment, and these descriptions are not to make further limit to present invention
It is fixed.It should be understood by those skilled in the art that the equivalent substitution made to the technical characteristic of the present invention, or be correspondingly improved, still belong to
Within protection scope of the present invention.
Specific embodiment mode
Embodiment 1
(1) synthesis of the fluoro- imidazos of 7- [1,2-a] pyridine -2- Ethyl formates
25g 2- amino -4- fluorine pyridines are added in 200ml glycol dimethyl ethers, add 54g3- ethyl bromide acetones, room
Temperature is stirred overnight, and concentration adds ethyl acetate and water, liquid separation, drying, concentration, the isolated 28g 7- of residue upper prop
Fluoro- imidazo [1,2-a] pyridine -2- Ethyl formates.
(2) synthesis of (the fluoro- imidazos of 7- [1,2-a] pyridine -2- bases) methanol
The fluoro- imidazos of 26g 7- [1,2-a] pyridine -2- Ethyl formates are added in 280ml absolute methanols, add 17g boron hydrogen
Change sodium, be stirred at room temperature 2 hours, add saturated ammonium chloride, add ethyl acetate and water, extract liquid separation, drying, concentration,
Silica gel post separation obtains 18g (the fluoro- imidazos of 7- [1,2-a] pyridine -2- bases) methanol on residue.
(3) synthesis of 2- (chloromethyl) -7- fluoro- imidazo [1,2-a] pyridine
16g (the fluoro- imidazos of 7- [1,2-a] pyridine -2- bases) methanol is added in 190ml toluene, adds 52g thionyl chlorides,
Stirring 3 hours is heated to reflux, concentration, adds ethyl acetate and saturated sodium bicarbonate aqueous solution, extracts liquid separation, is dried, concentration,
Silica gel post separation obtains 12g 2- (chloromethyl) -7- fluoro- imidazo [1,2-a] pyridine on residue.
Claims (5)
- A kind of 1. preparation method of fluorine-containing imidazopyridine derivatives 2- (chloromethyl) -7- fluoro- imidazo [1,2-a] pyridine, with 2- amino -4- Fluorine pyridine is initiation material, obtains target product 4 by cyclization, reduction, chlorination, 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 3- Ethyl bromide acetone；Reducing agent used in described reduction reaction prepare compound 3 be selected from sodium borohydride, potassium borohydride, One or more of mixtures in lithium borohydride, sodium cyanoborohydride, lithium aluminium hydride, borine；Described chlorination reaction Chlorinating agent used in prepare compound 4 in chlorine, hydrogen chloride, thionyl chloride, phosphorus trichloride, POCl3 one Kind or several mixtures.
- 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 first Alcohol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene, two One or more of mixtures in toluene, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, glycol dimethyl ether； Solvent used in described reduction reaction prepare compound 3 be selected from methanol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, Dichloromethane, toluene, ortho-xylene, paraxylene, meta-xylene, N,N-dimethylformamide, N, N- dimethyl second One or more of mixtures in acid amides, water；Solvent used in described chlorination reaction prepare compound 4 be selected from methanol, Ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene, meta-xylene, One or more of mixtures in N,N-dimethylformamide, DMAC N,N' dimethyl acetamide.
- 4. method according to claim 1, it is characterised in that the reaction temperature used in described ring closure reaction prepare compound 2 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 chlorination reaction prepare compound 4 is the reflux temperature of 0 DEG C~solvent.
- 5. method according to claim 1, it is characterised in that the reaction temperature used in described ring closure reaction prepare compound 2 is Room temperature；Temperature used in described reduction reaction prepare compound 3 is room temperature；Described chlorination reaction prepare compound 4 Used is the reflux temperature of solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610341530.1A CN107400127A (en) | 2016-05-20 | 2016-05-20 | A kind of preparation method of fluorine-containing imidazopyridine derivatives |
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| CN201610341530.1A CN107400127A (en) | 2016-05-20 | 2016-05-20 | A kind of preparation method of fluorine-containing imidazopyridine derivatives |
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| CN107400127A true CN107400127A (en) | 2017-11-28 |
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| CN201610341530.1A Withdrawn CN107400127A (en) | 2016-05-20 | 2016-05-20 | A kind of preparation method of fluorine-containing imidazopyridine derivatives |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104277042A (en) * | 2014-10-15 | 2015-01-14 | 湖南华腾制药有限公司 | Preparation method of imidazopyridine derivative |
| CN104628721A (en) * | 2015-01-22 | 2015-05-20 | 湖南华腾制药有限公司 | Preparation method of imidazo [1, 2-a] pyridine derivative |
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2016
- 2016-05-20 CN CN201610341530.1A patent/CN107400127A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104277042A (en) * | 2014-10-15 | 2015-01-14 | 湖南华腾制药有限公司 | Preparation method of imidazopyridine derivative |
| CN104628721A (en) * | 2015-01-22 | 2015-05-20 | 湖南华腾制药有限公司 | Preparation method of imidazo [1, 2-a] pyridine derivative |
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Application publication date: 20171128 |
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| WW01 | Invention patent application withdrawn after publication |