CN105153020A - Preparation method for aromatic azide - Google Patents
Preparation method for aromatic azide Download PDFInfo
- Publication number
- CN105153020A CN105153020A CN201510427012.7A CN201510427012A CN105153020A CN 105153020 A CN105153020 A CN 105153020A CN 201510427012 A CN201510427012 A CN 201510427012A CN 105153020 A CN105153020 A CN 105153020A
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- Prior art keywords
- reaction
- compound
- xylol
- mixture
- azido
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- WERKUGRMJFTANW-UHFFFAOYSA-N CCOC(CCC(CCCO)=N1)=C1Cl Chemical compound CCOC(CCC(CCCO)=N1)=C1Cl WERKUGRMJFTANW-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
Abstract
The invention discloses a synthetic method for an aromatic azide: 6-(3-azido propyl)-2-chloro-3-ethoxypyridine. The synthetic method comprises: by taking 3-(6-chloro-5-ethoxypyridine-2-yl) acrylic acid as a starting raw material, carrying out reduction, hydrogenation, passing through Ms and azido reaction to obtain a target product 5. The product is used as template small molecules to synthesize diverse compound libraries.
Description
Technical field
The present invention relates to a kind of novel method for synthesizing of medicine intermediate, particularly the synthetic method of a kind of aromatic azido compound 6-(3-Azidopropyl)-2-chloro-3-ethoxy pyridine.
Technical background
Compound 6-(3-Azidopropyl)-2-chloro-3-ethoxy pyridine, structural formula is:
This compound aromatic azido compound 1-(3-Azidopropyl)-3-chloro-4-phenetole and relevant derivative have widespread use in pharmaceutical chemistry and organic synthesis.The synthesis of current aromatic azido compound 1-(3-Azidopropyl)-3-chloro-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 synthetic method of a kind of aromatic azido compound 6-(3-Azidopropyl)-2-chloro-3-ethoxy pyridine, with 3-(the chloro-5-ethoxy pyridine of 6--2-base) 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 chloro-5-ethoxy pyridine of 6--2-base) 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 dichloride; 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 synthetic method of a kind of aromatic azido compound 6-(3-Azidopropyl)-2-chloro-3-ethoxy pyridine, there is no other Patents bibliographical informations at present.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of compound 6-(3-Azidopropyl)-2-chloro-3-ethoxy pyridine.
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 chloro-5-ethoxy pyridine of 6--2-base) the third-2-alkene-1-alcohol
16g3-(the chloro-5-ethoxy pyridine of 6--2-base) 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 7g3-(the chloro-5-ethoxy pyridine of 6--2-base) the third-2-alkene-1-alcohol.
(2) synthesis of 3-(the chloro-5-ethoxy pyridine of 6--2-base) the third-1-alcohol
7g3-(the chloro-5-ethoxy pyridine of 6--2-base) the third-2-alkene-1-alcohol is joined in 40ml methyl alcohol, adds 0.5g10% palladium carbon, pass into hydrogen, stirred overnight at room temperature, filters, and collects filtrate, concentrated, obtain 5g3-(the chloro-5-ethoxy pyridine of 6--2-base) the third-1-alcohol.
(3) synthesis of 3-(the chloro-5-ethoxy pyridine of 6--2-base) propyl Methanesulfonate
5g3-(the chloro-5-ethoxy pyridine of 6--2-base) the third-1-alcohol is joined in 50ml methylene dichloride, add 3g triethylamine, be cooled to 0 DEG C, add 2.9gMsCl, stirring at room temperature 2 hours, add water again, extraction separatory, collects organic phase, dry, concentrated, on residuum, silicagel column is separated to obtain 3.4g3-(the chloro-5-ethoxy pyridine of 6--2-base) propyl Methanesulfonate.
(4) synthesis of 6-(3-Azidopropyl)-2-chloro-3-ethoxy pyridine
3g3-(the chloro-5-ethoxy pyridine of 6--2-base) propyl Methanesulfonate is joined 30mlN, 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 2.5g6-(3-Azidopropyl)-2-chloro-3-ethoxy pyridine.
Claims (5)
1. the synthetic method of a kind of aromatic azido compound 6-(3-Azidopropyl)-2-chloro-3-ethoxy pyridine, with 3-(the chloro-5-ethoxy pyridine of 6--2-base) 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 chloro-5-ethoxy pyridine of 6--2-base) 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 dichloride, 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 dichloride, 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 dichloride, trichloromethane, 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 dichloride, 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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| CN201510427012.7A CN105153020A (en) | 2015-07-20 | 2015-07-20 | Preparation method for aromatic azide |
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| CN201510427012.7A CN105153020A (en) | 2015-07-20 | 2015-07-20 | Preparation method for aromatic azide |
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Cited By (1)
| 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 |
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2015
- 2015-07-20 CN CN201510427012.7A patent/CN105153020A/en active Pending
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| CN1376155A (en) * | 1999-07-30 | 2002-10-23 | 株式会社柳韩洋行 | Thiourea and isothiourea derivatives for inhibiting RAS-transformed cell growth |
| CN1438996A (en) * | 2000-05-31 | 2003-08-27 | 沃尼尔·朗伯公司 | Bicyclic cyclohexylamines and their use NMDA receptor antogonists |
| WO2001094321A1 (en) * | 2000-06-06 | 2001-12-13 | Warner-Lambert Company | Bicyclic cyclohexylamines and their use as nmda receptor antagonists |
| AU2008200036A1 (en) * | 2000-11-28 | 2008-01-31 | Applied Biosystems, Llc. | Sulfonated diarylrhodamine dyes |
| US20050153970A1 (en) * | 2003-11-13 | 2005-07-14 | Ko Soo S. | N-ureidoalkyl-amino compounds as modulators of chemokine receptor activity |
| WO2008106204A1 (en) * | 2007-02-28 | 2008-09-04 | Rib-X-Pharmaceuticals, Inc. | Macrolide compounds and methods of making and using the same |
| CN101784188A (en) * | 2007-06-29 | 2010-07-21 | 奥克塞拉有限公司 | alkynyl phenyl derivative compounds for treating ophthalmic diseases and disorders |
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| 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 |
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