CN104292157A - Preparation method of 1-(quinoline-4-yl) ethylamine - Google Patents
Preparation method of 1-(quinoline-4-yl) ethylamine Download PDFInfo
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- CN104292157A CN104292157A CN201410466495.7A CN201410466495A CN104292157A CN 104292157 A CN104292157 A CN 104292157A CN 201410466495 A CN201410466495 A CN 201410466495A CN 104292157 A CN104292157 A CN 104292157A
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- SUXIPCHEUMEUSV-UHFFFAOYSA-N Brc1c(cccc2)c2ncc1 Chemical compound Brc1c(cccc2)c2ncc1 SUXIPCHEUMEUSV-UHFFFAOYSA-N 0.000 description 1
- JBSAUEMFOKUWTP-UHFFFAOYSA-N N#Cc1c(cccc2)c2ncc1 Chemical compound N#Cc1c(cccc2)c2ncc1 JBSAUEMFOKUWTP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Quinoline Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method of 1-(quinoline-4-yl) ethylamine. A target product is obtained through bromination, cyaniding, grignard reaction and amination reduction by taking 4-hydroxyquinoline as an initial raw material, and the compound is an important medical intermediate.
Description
Technical field
The present invention relates to a kind of novel processing step of medicine intermediate, particularly a kind of preparation method of the preparation method of 1-(quinolyl-4) ethamine.
Technical background
Compound 1-(quinolyl-4) ethamine, structural formula is:
This compound 1-(quinolyl-4) ethamine and relevant derivative have widespread use in pharmaceutical chemistry and organic synthesis.The synthesis of current 1-(quinolyl-4) ethamine is comparatively difficult.Therefore, need exploitation raw material to be easy to get, easy to operate, reaction is easy to control, the synthetic method that overall yield is suitable.
Summary of the invention
The invention discloses the method that one prepares 1-(quinolyl-4) ethamine, with 4-hydroxyquinoline for starting raw material, obtain target product 5 through bromination, cyaniding, grignard reaction, amination reduction, synthetic route as shown in Figure 1.Synthesis step is as follows:
(1) 4-hydroxyquinoline is starting raw material, obtains 2 through bromination reaction;
(2) carry out cyanogenation 2, obtain 3;
(3) carry out grignard reaction 3 and obtain 4;
(4) carry out amination reduction reaction 4 and obtain target product 5,
One preferred embodiment in, the reagent that described bromination reaction prepares compound 2 used is selected from Hydrogen bromide; The alkali that described cyanogenation prepares compound 3 used is selected from salt of wormwood; Described grignard reaction is prepared compound 4 reagent used and is selected from methylpyridinium iodide magnesium; The reagent that described amination reduction reaction prepares compound 5 used is selected from sodium borohydride.
One preferred embodiment in, the solvent that described bromination reaction prepares compound 2 used is selected from toluene; The solvent that described cyanogenation prepares compound 3 used is selected from DMF; The solvent that described grignard reaction prepares compound 4 used is selected from tetrahydrofuran (THF); Described amination reduction reaction prepares compound 5 solvent selected from methanol used.
One preferred embodiment in, described bromination reaction prepares the reflux temperature that compound 2 temperature of reaction used is solvent; Described cyanogenation prepares the reflux temperature that compound 3 temperature used is solvent; It is 0 DEG C ~ room temperature that described grignard reaction prepares compound 4 temperature used; Described amination reduction reaction prepare compound 5 used be room temperature.
The present invention relates to the preparation method of a kind of 1-(quinolyl-4) ethamine, there is no other Patents bibliographical informations at present.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of compound 1-(quinolyl-4) ethamine.
The present invention is further described by the following embodiment, and these descriptions are not be further limited content of the present invention.One skilled in the art will understand that the equivalent replacement that technical characteristic of the present invention is done, or improve accordingly, still belong within protection scope of the present invention.
Specific embodiment mode
Embodiment 1
(1) synthesis of 4-bromoquinoline
25g4-hydroxyquinoline is joined in 150ml toluene, slowly adds 100ml Hydrogen bromide, return stirring 15 hours, concentrated, then add water and ethyl acetate, separatory, drying, concentrated, residuum upper prop is separated and obtains 29g4-bromoquinoline.
(2) synthesis of 4-cyano quinolines
28g4-bromoquinoline is joined 280ml N, in dinethylformamide, add 16g Anhydrous potassium carbonate, then add 21g cuprous cyanide, reheat backflow to spend the night, be cooled to room temperature, concentrated, then add water and methylene dichloride, extraction separatory, collect organic phase, separatory, drying, concentrated, on residuum, silicagel column is separated to obtain 21g4-cyano quinolines.
(3) synthesis of 4-acetoxyl group quinoline
20g4-cyano quinolines is joined in 160ml anhydrous tetrahydro furan, is cooled to 0 DEG C, drip 120ml methylpyridinium iodide magnesium (3M), naturally rise to room temperature, continue stirring 2 hours, then add water and ethyl acetate, filter, extraction separatory, concentrates and obtains 16g4-acetoxyl group quinoline.
(4) synthesis of 1-(quinolyl-4) ethamine
15g4-acetoxyl group quinoline is joined in 300ml methyl alcohol, add 120ml water, then add 18g oxammonium hydrochloride, then add 16g sodium hydroxide, stirring at room temperature 2 hours, add 9g sodium borohydride again, stirring at room temperature 3 hours, concentrated, add water and extraction into ethyl acetate, separatory, concentrated, on residuum, silicagel column is separated to obtain 11g1-(quinolyl-4) ethamine.
Claims (6)
1. prepare a preparation method for 1-(quinolyl-4) ethamine, with 4-hydroxyquinoline for starting raw material, obtain target product 5 through bromination, cyaniding, grignard reaction, amination reduction, synthetic route is as follows.
2. method according to claim 1, it is characterized by 4 described step reactions is,
(1) 4-hydroxyquinoline is starting raw material, obtains 2 through bromination reaction;
(2) carry out cyanogenation 2, obtain 3;
(3) carry out grignard reaction 3 and obtain 4;
(4) carry out amination reduction reaction 4 and obtain target product 5,
3. according to the method for claim 1-2, it is characterized in that, described bromination reaction is prepared compound 2 reagent used and is selected from the mixture of one or more in bromine, Hydrogen bromide, phosphorus tribromide, tribromo oxygen phosphorus; Described cyanogenation is prepared compound 3 alkali used and is selected from the mixture of one or more in sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, salt of wormwood, triethylamine, sodium bicarbonate, pyridine, triisopropylamine, saleratus; Described grignard reaction is prepared compound 4 reagent used and is selected from the mixture of one or more in methyl-magnesium-bromide, methylmagnesium-chloride, methylpyridinium iodide magnesium; Described amination reduction reaction is prepared compound 5 reagent used and is selected from the mixture of one or more in sodium borohydride, POTASSIUM BOROHYDRIDE, lithium borohydride, sodium cyanoborohydride, lithium aluminium hydride, borine.
4. according to the method for claim 1-2, it is characterized in that, described bromination reaction is prepared compound 2 solvent used and is selected from water, methyl alcohol, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene dichloride, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide; Described cyanogenation is prepared compound 3 solvent used and is selected from methylene dichloride, trichloromethane, ethyl acetate, tetrahydrofuran (THF), toluene, tetrahydrofuran (THF), toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, water; Described grignard reaction prepares compound 4 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene dichloride, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, water; Described amination reduction reaction prepares compound 5 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene dichloride, trichloromethane, ethyl acetate, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide.
5. according to the method for claim 1-2, it is characterized in that, described bromination reaction prepares the reflux temperature that compound 2 temperature of reaction used is 0 DEG C ~ solvent; Described cyanogenation prepares the reflux temperature that compound 3 temperature used is 0 DEG C ~ solvent; It is 0 DEG C ~ room temperature that described grignard reaction prepares compound 4 temperature used; Described amination reduction reaction prepare compound 5 used be 0 DEG C ~ room temperature.
6. according to the method for claim 1-2, it is characterized in that, described bromination reaction prepares the reflux temperature that compound 2 temperature of reaction used is solvent; Described cyanogenation prepares the reflux temperature that compound 3 temperature used is solvent; It is 0 DEG C ~ room temperature that described grignard reaction prepares compound 4 temperature used; Described amination reduction reaction prepare compound 5 used be 0 DEG C ~ room temperature.
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| CN201410466495.7A CN104292157A (en) | 2014-09-15 | 2014-09-15 | Preparation method of 1-(quinoline-4-yl) ethylamine |
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| CN201410466495.7A CN104292157A (en) | 2014-09-15 | 2014-09-15 | Preparation method of 1-(quinoline-4-yl) ethylamine |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104557868A (en) * | 2015-01-22 | 2015-04-29 | 湖南华腾制药有限公司 | Preparation method for quinoline derivatives |
| CN108285432A (en) * | 2017-01-10 | 2018-07-17 | 湖南华腾制药有限公司 | A kind of preparation method of quinoline |
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| WO2003099776A1 (en) * | 2002-05-23 | 2003-12-04 | Amgen Inc. | Calcium receptor modulating arylalkylamines |
| CN102898264A (en) * | 2012-09-12 | 2013-01-30 | 浙江大学 | Catalytic preparation process for aromatic nitrile or heteroaromatic nitrile |
| WO2014099837A1 (en) * | 2012-12-18 | 2014-06-26 | E. I. Du Pont De Nemours And Company | Sulfonamide anthelmintics |
| WO2014121883A1 (en) * | 2013-02-07 | 2014-08-14 | Merck Patent Gmbh | Substituted acetylene derivatives and their use as positive allosteric modulators of mglur4 |
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2014
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2003099776A1 (en) * | 2002-05-23 | 2003-12-04 | Amgen Inc. | Calcium receptor modulating arylalkylamines |
| CN102898264A (en) * | 2012-09-12 | 2013-01-30 | 浙江大学 | Catalytic preparation process for aromatic nitrile or heteroaromatic nitrile |
| WO2014099837A1 (en) * | 2012-12-18 | 2014-06-26 | E. I. Du Pont De Nemours And Company | Sulfonamide anthelmintics |
| WO2014121883A1 (en) * | 2013-02-07 | 2014-08-14 | Merck Patent Gmbh | Substituted acetylene derivatives and their use as positive allosteric modulators of mglur4 |
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| BRANDON J. MARGOLIS等: "Assembly of 4-Aminoquinolines via Palladium Catalysis: A Mild and Convenient Alternative to SNAr Methodology", 《J. ORG. CHEM.》, vol. 72, no. 6, 13 February 2007 (2007-02-13), pages 2232 - 2235 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104557868A (en) * | 2015-01-22 | 2015-04-29 | 湖南华腾制药有限公司 | Preparation method for quinoline derivatives |
| CN108285432A (en) * | 2017-01-10 | 2018-07-17 | 湖南华腾制药有限公司 | A kind of preparation method of quinoline |
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