CN104341344A - Preparation method of 3-(2-methylquinoline-6-yl) propionamide - Google Patents
Preparation method of 3-(2-methylquinoline-6-yl) propionamide Download PDFInfo
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- CN104341344A CN104341344A CN201410545179.9A CN201410545179A CN104341344A CN 104341344 A CN104341344 A CN 104341344A CN 201410545179 A CN201410545179 A CN 201410545179A CN 104341344 A CN104341344 A CN 104341344A
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- Prior art keywords
- compound
- temperature
- xylol
- mixture
- ring closure
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- 0 Cc1nc2ccc(CC*)cc2cc1 Chemical compound Cc1nc2ccc(CC*)cc2cc1 0.000 description 1
Classifications
-
- 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
Abstract
The invention discloses a preparation method of 3-(2-methylquinoline-6-yl) propionamide. A target product is obtained by taking ethyl 4-aminocinnamate as a starting raw material and performing reduction, cyclization and amidation, and the compound is an important pharmaceutical intermediate.
Description
Technical field
The present invention relates to a kind of novel processing step of medicine intermediate, particularly the preparation method of a kind of 3-(2-toluquinoline-6-base) propionic acid amide.
Technical background
Compound 3-(2-toluquinoline-6-base) propionic acid amide, structural formula is:
This compound 3-(2-toluquinoline-6-base) propionic acid amide and relevant derivative have widespread use in pharmaceutical chemistry and organic synthesis.The synthesis of current 3-(2-toluquinoline-6-base) propionic acid amide 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 3-(2-toluquinoline-6-base) propionic acid amide, with 4-amino cinnamate for starting raw material, obtain target product 4 through reduction, Guan Huan, amidation, synthetic route as shown in Figure 1.Synthesis step is as follows:
(1) with 4-amino cinnamate for starting raw material, obtain 2 through reduction reaction;
(2) carry out ring closure reaction 2, obtain 3;
(3) carry out amidate action 3 and obtain 4;
One preferred embodiment in, described reduction reaction is prepared compound 2 reductive agent used and is selected from palladium carbon-hydrogen; The reagent that described ring closure reaction prepares compound 3 used is selected from p-methyl benzenesulfonic acid; The reagent that described amidate action prepares compound 4 used is selected from ammoniacal liquor.
One preferred embodiment in, described reduction reaction prepares compound 2 solvent selected from methanol used; The solvent that described ring closure reaction prepares compound 3 used is selected from acetic acid; The solvent that described amidate action prepares compound 4 used is selected from ammoniacal liquor.
One preferred embodiment in, it is room temperature that described reduction reaction prepares compound 2 temperature of reaction used; Described ring closure reaction prepares the reflux temperature that compound 3 temperature used is solvent; Described amidate action prepare compound 4 used be 150 DEG C.
The present invention relates to the preparation method of a kind of 3-(2-toluquinoline-6-base) propionic acid amide, there is no other Patents bibliographical informations at present.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of compound 3-(2-toluquinoline-6-base) propionic acid amide.
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 3-(4-aminophenyl) methyl propionate
5g 4-amino cinnamate is joined in 110ml methyl alcohol, adds 0.2g palladium carbon, pass into hydrogen, stirred overnight at room temperature, filter, filtrate concentrates, and obtains 4.8g 3-(4-aminophenyl) methyl propionate.
(2) synthesis of 3-(2-toluquinoline-6-base) methyl propionate
4.5g 3-(4-aminophenyl) methyl propionate is joined in 90ml acetic acid, add 7g iron trichloride and 3.8g crotonic aldehyde again, reflux stirs 2 hours, cooling, add 10% aqueous sodium hydroxide solution and adjust pH to 10, add dichloromethane extraction, concentrated, residuum upper prop is separated to obtain 2.7g 3-(2-toluquinoline-6-base) methyl propionate.
(3) synthesis of 3-(2-toluquinoline-6-base) propionic acid amide
2.5g3-(2-toluquinoline-6-base) methyl propionate is joined in 30ml ammoniacal liquor, be heated to 150 DEG C stir 6 hours, be cooled to room temperature, concentrated, add ethyl acetate and the aqueous solution, extraction separatory, dry, concentrated, on residuum, silicagel column is separated to obtain 1.7g 3-(2-toluquinoline-6-base) propionic acid amide.
Claims (6)
1. a preparation method for 3-(2-toluquinoline-6-base) propionic acid amide, with 4-amino cinnamate for starting raw material, obtain target product 4 through reduction, Guan Huan, amidation, synthetic route is as follows.
2. method according to claim 1, it is characterized by 3 described step reactions is,
(1) with 4-amino cinnamate for starting raw material, obtain 2 through reduction reaction;
(2) carry out ring closure reaction 2, obtain 3;
(3) carry out amidate action 3 and obtain 4;
3. according to the method for claim 1-2, it is characterized in that, described reduction reaction is prepared compound 2 reductive agent used and is selected from one or both mixture in sodium borohydride, POTASSIUM BOROHYDRIDE, lithium borohydride, sodium cyanoborohydride, lithium aluminium hydride, borine, iron powder, zinc powder, palladium carbon-hydrogen, nickel-hydrogen; Described ring closure reaction is prepared compound 3 Lewis acid used and is selected from the mixture of one or more in iron trichloride, tin chloride, zinc chloride; Described amidate action is prepared compound 4 reagent used and is selected from the mixture of one or more in ammoniacal liquor, ammonia, ammonium chloride.
4. according to the method for claim 1-2, it is characterized in that, described reduction reaction prepares compound 2 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, acetic acid, chloroform; Described ring closure reaction prepares compound 3 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, acetic acid, formic acid; Described amidate action 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, ammoniacal liquor.
5. according to the method for claim 1-2, it is characterized in that, described reduction reaction prepares the reflux temperature that compound 2 temperature of reaction used is 0 DEG C ~ solvent; Described ring closure reaction prepares the reflux temperature that compound 3 temperature used is 0 DEG C ~ solvent; It is room temperature ~ 200 DEG C that described amidate action prepares compound 4 temperature used.
6. according to the method for claim 1-2, it is characterized in that, it is room temperature that described reduction reaction prepares compound 2 temperature of reaction used; It is room temperature that described ring closure reaction prepares compound 3 temperature used; Described amidate action prepare compound 4 used be 150 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410545179.9A CN104341344A (en) | 2014-10-16 | 2014-10-16 | Preparation method of 3-(2-methylquinoline-6-yl) propionamide |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410545179.9A CN104341344A (en) | 2014-10-16 | 2014-10-16 | Preparation method of 3-(2-methylquinoline-6-yl) propionamide |
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| CN104341344A true CN104341344A (en) | 2015-02-11 |
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| CN201410545179.9A Pending CN104341344A (en) | 2014-10-16 | 2014-10-16 | Preparation method of 3-(2-methylquinoline-6-yl) propionamide |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107176922A (en) * | 2016-03-09 | 2017-09-19 | 湖南华腾制药有限公司 | A kind of synthetic method of quinoline |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007092364A2 (en) * | 2006-02-07 | 2007-08-16 | Merck & Co., Inc. | Niacin receptor agonists, compositions containing such compounds and methods of treatment |
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2014
- 2014-10-16 CN CN201410545179.9A patent/CN104341344A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007092364A2 (en) * | 2006-02-07 | 2007-08-16 | Merck & Co., Inc. | Niacin receptor agonists, compositions containing such compounds and methods of treatment |
Non-Patent Citations (2)
| Title |
|---|
| B. BOHMAN 等: "Structure–Activity Relationships of Phenylpropanoids as Antifeedants for the Pine Weevil Hylobius abietis", 《J CHEM ECOL》 * |
| 王振宇 等: "基于喹啉与苯胺衍生物不对称方酸菁染料的合成与光谱性质", 《有机化学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107176922A (en) * | 2016-03-09 | 2017-09-19 | 湖南华腾制药有限公司 | A kind of synthetic method of quinoline |
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Application publication date: 20150211 |