CN105001118A - Method for preparing iodine-containing azido compound - Google Patents
Method for preparing iodine-containing azido compound Download PDFInfo
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- CN105001118A CN105001118A CN201510427724.9A CN201510427724A CN105001118A CN 105001118 A CN105001118 A CN 105001118A CN 201510427724 A CN201510427724 A CN 201510427724A CN 105001118 A CN105001118 A CN 105001118A
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Abstract
The invention discloses a method for preparing 3-iodophenyl azido compound, namely 1-(3-azido propyl group)-3-iodine-4-ethoxy benzene, wherein 3-(3- iodine-4-ethoxy phenyl)acrylic acid is adopted as the initial raw material and a target product 5 is obtained through the steps of reduction, hydrogenation, mass spectrometry and azido reaction. According to the technical scheme of the invention, the product of the method is adopted as a low-molecular template for the synthesis of a wide variety of compound libraries.
Description
Technical field
The present invention relates to a kind of novel processing step of medicine intermediate, particularly the preparation method of the iodo-4-phenetole of a kind of 3-iodophenyl triazo-compound 1-(3-Azidopropyl)-3-.
Technical background
The iodo-4-phenetole of compound 1-(3-Azidopropyl)-3-, structural formula is:
This compound 3-iodophenyl triazo-compound 1-(3-Azidopropyl)-3-iodo-4-phenetole and relevant derivative have widespread use in pharmaceutical chemistry and organic synthesis.The synthesis of current 3-iodophenyl triazo-compound 1-(3-Azidopropyl)-3-iodo-4-phenetole 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 preparation method of the iodo-4-phenetole of a kind of 3-iodophenyl triazo-compound 1-(3-Azidopropyl)-3-, with 3-(the iodo-4-ethoxyl phenenyl of 3-) vinylformic acid for starting raw material, obtain target product 5 through reduction, hydrogenation, upper Ms, azido reaction, synthetic route as shown in Figure 1.Synthesis step is as follows:
(1) 3-(the iodo-4-ethoxyl phenenyl of 3-) vinylformic acid is starting raw material, obtains 2 through reduction reaction,
(2) carry out hydrogenation reaction 2, obtain 3,
(3) carry out upper Ms 3 and be obtained by reacting 4,
(4) carry out azido reaction 4 and obtain 5,
One preferred embodiment in, described reduction reaction is prepared compound 2 reagent used and is selected from Lithium Aluminium Hydride; Described hydrogenation reaction is prepared compound 3 reagent used and is selected from palladium carbon; Described upper Ms reacts the reagent preparing compound 4 used and is selected from triethylamine; The reagent that described azido reaction prepares compound 5 used is selected from sodiumazide.
One preferred embodiment in, the solvent that described reduction reaction prepares compound 2 used is selected from tetrahydrofuran (THF); Described hydrogenation reaction prepares compound 3 solvent selected from methanol used; Described upper Ms reacts the solvent preparing compound 4 used and is selected from methylene iodide; The solvent that described azido reaction prepares compound 5 used is selected from DMF.
One preferred embodiment in, described reduction reaction prepare compound 2 temperature of reaction used be 0 DEG C to room temperature; It is room temperature that described hydrogenation reaction prepares compound 3 temperature used; Described upper Ms reaction prepare compound 4 temperature used be 0 DEG C to room temperature; It is room temperature that described azido reaction prepares compound 5 temperature used.
The present invention relates to the preparation method of the iodo-4-phenetole of a kind of 3-iodophenyl triazo-compound 1-(3-Azidopropyl)-3-, there is no other Patents bibliographical informations at present.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of the iodo-4-phenetole of compound 1-(3-Azidopropyl)-3-.
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-(the iodo-4-ethoxyl phenenyl of 3-) third-2-alkene-1-alcohol
16g 3-(the iodo-4-ethoxyl phenenyl of 3-) vinylformic acid is joined in 200ml tetrahydrofuran (THF), be cooled to 0 DEG C, slowly add 6g Lithium Aluminium Hydride in batches, stirred overnight at room temperature, adds water and ethyl acetate, extraction separatory, collect organic phase, drying, concentrated, obtain 7g 3-(the iodo-4-ethoxyl phenenyl of 3-) third-2-alkene-1-alcohol.
(2) synthesis of 3-(the iodo-4-ethoxyl phenenyl of 3-) the third-1-alcohol
7g 3-(the iodo-4-ethoxyl phenenyl of 3-) third-2-alkene-1-alcohol is joined in 40ml methyl alcohol, adds 0.5g 10% palladium carbon, pass into hydrogen, stirred overnight at room temperature, filters, and collects filtrate, concentrated, obtain 5g 3-(the iodo-4-ethoxyl phenenyl of 3-) the third-1-alcohol.
(3) synthesis of 3-(the iodo-4-ethoxyl phenenyl of 3-) propyl Methanesulfonate
5g 3-(the iodo-4-ethoxyl phenenyl of 3-) the third-1-alcohol is joined in 50ml methylene iodide, add 3g triethylamine, be cooled to 0 DEG C, add 2.9g MsCl, stirring at room temperature 2 hours, add water again, extraction separatory, collects organic phase, dry, concentrated, on residuum, silicagel column is separated to obtain 3.4g 3-(the iodo-4-ethoxyl phenenyl of 3-) propyl Methanesulfonate.
(4) synthesis of the iodo-4-phenetole of 1-(3-Azidopropyl)-3-
3g 3-(the iodo-4-ethoxyl phenenyl of 3-) propyl Methanesulfonate is joined 30ml N, in dinethylformamide, add 4g sodiumazide, stirring at room temperature 6 hours, adds water and ethyl acetate, extraction separatory, collect organic phase, drying, concentrated, on residuum, silicagel column is separated to obtain the iodo-4-phenetole of 2.5g 1-(3-Azidopropyl)-3-.
Claims (5)
1. the preparation method of the iodo-4-phenetole of a kind of 3-iodophenyl triazo-compound 1-(3-Azidopropyl)-3-, with 3-(the iodo-4-ethoxyl phenenyl of 3-) vinylformic acid for starting raw material, obtain target product 5 through reduction, hydrogenation, upper Ms, azido reaction, synthetic route is as follows:
2. method according to claim 1, it is characterized by 4 described step reactions is,
(1) 3-(the iodo-4-ethoxyl phenenyl of 3-) vinylformic acid is starting raw material, obtains 2 through reduction reaction,
(2) carry out hydrogenation reaction 2, obtain 3,
(3) carry out upper Ms 3 and be obtained by reacting 4,
(4) carry out azido reaction 4 and obtain 5,
3. according to the method for claim 1-2, it is characterized in that, described reduction reaction is prepared compound 2 reagent used and is selected from one or both mixture in borine, Lithium Aluminium Hydride; Described hydrogenation reaction is prepared compound 3 reagent used and is selected from the mixture of one or more in palladium carbon, palladium hydroxide, Raney's nickel; Described upper Ms reaction is prepared compound 4 reagent used and is selected from the mixture of one or more in triethylamine, pyridine, salt of wormwood, sodium hydroxide; The reagent that described azido reaction prepares compound 5 used is selected from sodiumazide.
4. according to the method for claim 1-2, it is characterized in that, described reduction reaction is prepared compound 2 solvent used and is selected from tetrahydrofuran (THF), methylene iodide, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, acetonitrile; Described hydrogenation reaction prepares compound 3 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene iodide, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, acetonitrile; Compound 4 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, acetonitrile, tetrahydrofuran (THF), dioxane, methylene iodide, triiodomethane, toluene, o-Xylol, p-Xylol, m-xylene, N are prepared in described upper Ms reaction, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide; Described azido reaction prepares compound 5 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene iodide, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, acetonitrile.
5. according to the method for claim 1-2, it is characterized in that, it is 0 DEG C of reflux temperature to solvent that described reduction reaction prepares compound 2 temperature of reaction used; It is room temperature that described hydrogenation reaction prepares compound 3 temperature used; It is 0 DEG C of reflux temperature to solvent that compound 4 temperature used is prepared in described upper Ms reaction; It is room temperature that described azido reaction prepares compound 5 temperature used.
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| CN201510427724.9A CN105001118A (en) | 2015-07-20 | 2015-07-20 | Method for preparing iodine-containing azido compound |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106883140A (en) * | 2017-02-26 | 2017-06-23 | 长沙深橙生物科技有限公司 | A kind of preparation method containing azido micromolecular compound |
| WO2018084625A1 (en) * | 2016-11-04 | 2018-05-11 | St Pharm Co., Ltd. | Method for preparation of (s)-n1-(2-aminoethyl)-3-(4-alkoxyphenyl)propane-1,2-diamine trihydrochloride |
| CN108117514A (en) * | 2016-11-29 | 2018-06-05 | 湖南华腾制药有限公司 | A kind of preparation method of pyridine azido compound |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1438996A (en) * | 2000-05-31 | 2003-08-27 | 沃尼尔·朗伯公司 | Bicyclic cyclohexylamines and their use NMDA receptor antogonists |
| WO2004043903A1 (en) * | 2002-11-05 | 2004-05-27 | Eli Lilly And Company | 3-aryloxy/ thio-2, 3-substituted propanamines and their use in inhibiting serotonin and norepinephrine reuptake |
| WO2008106204A1 (en) * | 2007-02-28 | 2008-09-04 | Rib-X-Pharmaceuticals, Inc. | Macrolide compounds and methods of making and using the same |
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2015
- 2015-07-20 CN CN201510427724.9A patent/CN105001118A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1438996A (en) * | 2000-05-31 | 2003-08-27 | 沃尼尔·朗伯公司 | Bicyclic cyclohexylamines and their use NMDA receptor antogonists |
| WO2004043903A1 (en) * | 2002-11-05 | 2004-05-27 | Eli Lilly And Company | 3-aryloxy/ thio-2, 3-substituted propanamines and their use in inhibiting serotonin and norepinephrine reuptake |
| WO2008106204A1 (en) * | 2007-02-28 | 2008-09-04 | Rib-X-Pharmaceuticals, Inc. | Macrolide compounds and methods of making and using the same |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018084625A1 (en) * | 2016-11-04 | 2018-05-11 | St Pharm Co., Ltd. | Method for preparation of (s)-n1-(2-aminoethyl)-3-(4-alkoxyphenyl)propane-1,2-diamine trihydrochloride |
| US10501403B2 (en) | 2016-11-04 | 2019-12-10 | St Pharm Co., Ltd. | Method for preparation of (S)-N1-(2-aminoethyl)-3-(4-alkoxyphenyl)propane-1,2-diamine trihydrochloride |
| CN108117514A (en) * | 2016-11-29 | 2018-06-05 | 湖南华腾制药有限公司 | A kind of preparation method of pyridine azido compound |
| CN106883140A (en) * | 2017-02-26 | 2017-06-23 | 长沙深橙生物科技有限公司 | A kind of preparation method containing azido micromolecular compound |
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Application publication date: 20151028 |