CN105622578A - Preparation method of indole amide compound - Google Patents
Preparation method of indole amide compound Download PDFInfo
- Publication number
- CN105622578A CN105622578A CN201610114918.8A CN201610114918A CN105622578A CN 105622578 A CN105622578 A CN 105622578A CN 201610114918 A CN201610114918 A CN 201610114918A CN 105622578 A CN105622578 A CN 105622578A
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- CN
- China
- Prior art keywords
- preparation
- compound according
- indole amides
- amides compound
- indole
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- KRTLKPFLTASKCG-UHFFFAOYSA-N NNc1ccncc1 Chemical compound NNc1ccncc1 KRTLKPFLTASKCG-UHFFFAOYSA-N 0.000 description 1
- XEEANGGQJOWRTG-UHFFFAOYSA-N OCc1cc2ccccc2[nH]1 Chemical compound OCc1cc2ccccc2[nH]1 XEEANGGQJOWRTG-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method of an indole amide compound. The method is characterized in that according to the reaction mechanism, a compound I (please see the formula in the description) and a compound II (please see the formula in the description) react to generate a compound III (please see the formula in the description) after being catalyzed through a catalyst, wherein R represents an alky group of C1-C6, an aryl group or a heteroaryl group. The efficient multi-component catalyst system is adopted, and the yield of the prepared target product is high. In addition, the preparation method is easy to operate and high in production efficiency, the conditions of the environment required for reaction are mild, and the method is quite suitable for large-scale industrialized production.
Description
Technical field:
The present invention relates to organic chemical synthesis field, specifically relate to the preparation method of a kind of indole amides compound.
Background technology:
Indole amides compounds all plays important effect in medical chemistry, agrochemistry and biochemical field, and especially it is as acceptor in inhibitory enzyme activity or metal ion detection etc., and indole amides compounds is effect all significantly. And indole amides compounds is easily absorbed metabolism by human body, human body can not be damaged while playing drug effect. Therefore, how to prepare the focus that indole amides compounds becomes research at present efficiently.
Chinese patent 201510246077.1 describes a kind of two indole amides acceptor and its preparation method and application, by indoles is dissolved in anhydrous diethyl ether, ice-water bath slowly adds under violent stirring oxalyl chloride, react after 1 hour, reaction solution is taken out filter, throw out after taking out filter is washed, obtains intermediate indole acyl chlorides; By intermediate indole acid chloride dissolves in ethyl acetate, add hydrazine hydrate, dropwise add phase-transfer catalyst PEG-400 again, after stirred at ambient temperature reacts 10 minutes, adding the NaOH solution of mass concentration 5% again, stirred at ambient temperature reacts 1 hour, and reaction solution is taken out filter, the washing of the throw out after filter, dry will be taken out, obtain two indole amides acceptor crude product. This pair of indole amides by physical efficiency efficiently, detection and Identification lead ion fast, in fields such as biological, medicine and environment, there is important effect. But, in current prior art, the preparation method of indole amides compound is still quick not, efficiently.
Summary of the invention:
The present invention relates to the preparation method of a kind of indole amides compound, have employed efficient multi-component catalyst systems, obtained target product yield height. Further, this preparation method is simple to operate, production efficiency height, and the required envrionment conditions of reaction is gentle, and very applicable large-scale industrial production uses.
For achieving the above object, the present invention is by the following technical solutions:
The preparation method of a kind of indole amides compound, it is characterised in that, reaction mechanism is as follows: in acid condition, by chemical compounds I and compound ii after catalyst, reacts, and generates compound III.
Wherein R is C1-C6Alkyl, aryl or heteroaryl.
Preferred as technique scheme, wherein said aryl is benzene, toluene or naphthalene.
Preferred as technique scheme, wherein said heteroaryl is pyridine or pyrans.
Preferred as technique scheme, the concrete operation steps of wherein said preparation method is: be dissolved in dimethyl sulfoxide (DMSO) by chemical compounds I and compound ii, add organic acid, adjustment pH is 3-4, add catalyzer and clorox more wherein, increase the temperature to 70-90 DEG C, add with 70-90 turn/rotating speed of min stirs, after sustained reaction 18h, reaction terminates; Filter, filtrate is adjusted to neutrality, after adding acetone extract, dry concentrated, cross silica gel column chromatography, obtain compound III with the methylene dichloride of equal-volume ratio-sherwood oil mixed solution after rinsing.
Preferred as technique scheme, wherein said organic acid is the one in oxalic acid, citric acid or Whitfield's ointment.
Preferred as technique scheme, wherein said catalyzer is that two (triphenylphosphine) nitric acid is cuprous, the mixture of trifluoromethanesulfonic acid nickel and phthalocyanine.
Preferred as technique scheme, in wherein said catalyzer, two (triphenylphosphine) nitric acid is cuprous, the mol ratio of trifluoromethanesulfonic acid nickel and phthalocyanine is 1:2:3.
Preferred as technique scheme, the mol ratio of wherein said chemical compounds I and compound ii is 1:1.4-1.8.
Preferred as technique scheme, the mol ratio of wherein said chemical compounds I and catalyzer is 1:0.09-0.15.
Preferred as technique scheme, the mol ratio of wherein said chemical compounds I and clorox is 1:1.5-2.
The present invention has following useful effect:
The preparation method of indole amides compound of the present invention, have employed novel three components catalyzer, reacts under sour environment, improve the output efficiency of object product, and improve speed of response, the required envrionment conditions of reaction is gentle, very applicable large-scale industrial production.
Embodiment:
For a better understanding of the present invention, below by embodiment, the present invention is further described, and the present invention, only for explaining the present invention, can not be formed any restriction by embodiment.
Embodiment 1
By formula chemical compounds I on 100mmol and on 150mmol formula compound ii be dissolved in dimethyl sulfoxide (DMSO), add citric acid, adjustment pH is 3-4, add 13mmol catalyzer and 150mmol clorox more wherein, increase the temperature to 80 DEG C, adding and stir with the rotating speed of 90 turns/min, after sustained reaction 18h, reaction terminates; Filter, filtrate is adjusted to neutrality, after adding acetone extract, dry concentrated, cross silica gel column chromatography, obtain upper formula compound III after rinsing with the methylene dichloride of equal-volume ratio-sherwood oil mixed solution. The product rate of target product is 97.5%
Embodiment 2
By formula chemical compounds I on 100mmol and on 180mmol formula compound ii be dissolved in dimethyl sulfoxide (DMSO), add Whitfield's ointment, adjustment pH is 3-4, add 11mmol catalyzer and 160mmol clorox more wherein, increase the temperature to 80 DEG C, adding and stir with the rotating speed of 70 turns/min, after sustained reaction 18h, reaction terminates; Filter, filtrate is adjusted to neutrality, after adding acetone extract, dry concentrated, cross silica gel column chromatography, obtain upper formula compound III after rinsing with the methylene dichloride of equal-volume ratio-sherwood oil mixed solution. The product rate of target product is 96.7%.
Embodiment 3
By formula chemical compounds I on 100mmol and on 140mmol formula compound ii be dissolved in dimethyl sulfoxide (DMSO), add oxalic acid, adjustment pH is 3-4, add 10mmol catalyzer and 150mmol clorox more wherein, increase the temperature to 90 DEG C, adding and stir with the rotating speed of 70 turns/min, after sustained reaction 18h, reaction terminates; Filter, filtrate is adjusted to neutrality, after adding acetone extract, dry concentrated, cross silica gel column chromatography, obtain upper formula compound III after rinsing with the methylene dichloride of equal-volume ratio-sherwood oil mixed solution. The product rate of target product is 98.1%.
Embodiment 4
By formula chemical compounds I on 100mmol and on 150mmol formula compound ii be dissolved in dimethyl sulfoxide (DMSO), add oxalic acid, adjustment pH is 3-4, add 10mmol catalyzer and 170mmol clorox more wherein, increase the temperature to 80 DEG C, adding and stir with the rotating speed of 80 turns/min, after sustained reaction 18h, reaction terminates; Filter, filtrate is adjusted to neutrality, after adding acetone extract, dry concentrated, cross silica gel column chromatography, obtain upper formula compound III after rinsing with the methylene dichloride of equal-volume ratio-sherwood oil mixed solution. The product rate of target product is 96.2%.
Embodiment 5
By formula chemical compounds I on 100mmol and on 160mmol formula compound ii be dissolved in dimethyl sulfoxide (DMSO), add Whitfield's ointment, adjustment pH is 3-4, add 12mmol catalyzer and 200mmol clorox more wherein, increase the temperature to 90 DEG C, adding and stir with the rotating speed of 90 turns/min, after sustained reaction 18h, reaction terminates; Filter, filtrate is adjusted to neutrality, after adding acetone extract, dry concentrated, cross silica gel column chromatography, obtain upper formula compound III after rinsing with the methylene dichloride of equal-volume ratio-sherwood oil mixed solution. The product rate of target product is 97.9%.
Embodiment 6
By formula chemical compounds I on 100mmol and on 170mmol formula compound ii be dissolved in dimethyl sulfoxide (DMSO), add Whitfield's ointment, adjustment pH is 3-4, add 14mmol catalyzer and 150mmol clorox more wherein, increase the temperature to 80 DEG C, adding and stir with the rotating speed of 80 turns/min, after sustained reaction 18h, reaction terminates; Filter, filtrate is adjusted to neutrality, after adding acetone extract, dry concentrated, cross silica gel column chromatography, obtain upper formula compound III after rinsing with the methylene dichloride of equal-volume ratio-sherwood oil mixed solution. The product rate of target product is 98.2%.
Claims (10)
1. the preparation method of an indole amides compound, it is characterised in that, reaction mechanism is as follows: in acid condition, by chemical compounds I and compound ii after catalyst, reacts, and generates compound III.
Wherein R is C1-C6Alkyl, aryl or heteroaryl.
2. the preparation method of indole amides compound according to claim 1, it is characterised in that, wherein said aryl is benzene, toluene or naphthalene.
3. the preparation method of indole amides compound according to claim 1, it is characterised in that, wherein said heteroaryl is pyridine or pyrans.
4. the preparation method of indole amides compound according to claim 1, it is characterized in that, the concrete operation steps of wherein said preparation method is: be dissolved in dimethyl sulfoxide (DMSO) by chemical compounds I and compound ii, adding organic acid, adjustment pH is 3-4, then adds catalyzer and clorox wherein, increase the temperature to 70-90 DEG C, add with 70-90 turn/rotating speed of min stirs, after sustained reaction 18h, reaction terminates; Filter, filtrate is adjusted to neutrality, after adding acetone extract, dry concentrated, cross silica gel column chromatography, obtain compound III with the methylene dichloride of equal-volume ratio-sherwood oil mixed solution after rinsing.
5. the preparation method of indole amides compound according to claim 4, it is characterised in that, wherein said organic acid is the one in oxalic acid, citric acid or Whitfield's ointment.
6. the preparation method of indole amides compound according to claim 4, it is characterised in that, wherein said catalyzer is that two (triphenylphosphine) nitric acid is cuprous, the mixture of trifluoromethanesulfonic acid nickel and phthalocyanine.
7. the preparation method of indole amides compound according to claim 4, it is characterised in that, in wherein said catalyzer, two (triphenylphosphine) nitric acid is cuprous, the mol ratio of trifluoromethanesulfonic acid nickel and phthalocyanine is 1:2:3.
8. the preparation method of indole amides compound according to claim 4, it is characterised in that, the mol ratio of wherein said chemical compounds I and compound ii is 1:1.4-1.8.
9. the preparation method of indole amides compound according to claim 4, it is characterised in that, the mol ratio of wherein said chemical compounds I and catalyzer is 1:0.09-0.15.
10. the preparation method of indole amides compound according to claim 4, it is characterised in that, the mol ratio of wherein said chemical compounds I and clorox is 1:1.5-2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610114918.8A CN105622578A (en) | 2016-03-01 | 2016-03-01 | Preparation method of indole amide compound |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610114918.8A CN105622578A (en) | 2016-03-01 | 2016-03-01 | Preparation method of indole amide compound |
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| CN105622578A true CN105622578A (en) | 2016-06-01 |
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| CN201610114918.8A Pending CN105622578A (en) | 2016-03-01 | 2016-03-01 | Preparation method of indole amide compound |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101624323A (en) * | 2009-07-29 | 2010-01-13 | 四川大学 | Preparation method of primary amine and secondary amine compound |
| CN104926708A (en) * | 2015-05-15 | 2015-09-23 | 四川理工学院 | Bisindole amide receptor, preparation method therefor and application thereof |
-
2016
- 2016-03-01 CN CN201610114918.8A patent/CN105622578A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101624323A (en) * | 2009-07-29 | 2010-01-13 | 四川大学 | Preparation method of primary amine and secondary amine compound |
| CN104926708A (en) * | 2015-05-15 | 2015-09-23 | 四川理工学院 | Bisindole amide receptor, preparation method therefor and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| MATTHIAS MENTEL ET AL.: "An Environmentally Benign Electrochemical Process for the Reduction of Carboxylic Acid Hydrazides to Amides", 《SYNTHESIS》 * |
| MINGZHAO ZHU ET AL.: "Photoinduced Cleavage of N–N Bonds of Aromatic Hydrazines and Hydrazides by Visible Light", 《SYNTHESIS》 * |
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Application publication date: 20160601 |