CN106831616A - A kind of preparation method of triazole class compounds - Google Patents
A kind of preparation method of triazole class compounds Download PDFInfo
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- CN106831616A CN106831616A CN201611141606.2A CN201611141606A CN106831616A CN 106831616 A CN106831616 A CN 106831616A CN 201611141606 A CN201611141606 A CN 201611141606A CN 106831616 A CN106831616 A CN 106831616A
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- prepare compound
- xylene
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- reaction prepare
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- 0 CCOC(CCc1ccc(*O)cc1)=O Chemical compound CCOC(CCc1ccc(*O)cc1)=O 0.000 description 3
- FTRNZSWZNKDYGD-UHFFFAOYSA-N CCCN(CCC)Cc1nc(CCc(cc2)ccc2[N+]([O-])=O)n[nH]1 Chemical compound CCCN(CCC)Cc1nc(CCc(cc2)ccc2[N+]([O-])=O)n[nH]1 FTRNZSWZNKDYGD-UHFFFAOYSA-N 0.000 description 1
- PDDLWLBTSBEAHE-UHFFFAOYSA-N CCCNC(CCc(cc1)ccc1[N+]([O-])=O)=O Chemical compound CCCNC(CCc(cc1)ccc1[N+]([O-])=O)=O PDDLWLBTSBEAHE-UHFFFAOYSA-N 0.000 description 1
- DPRVNPIXZSEART-AIUUQRTRSA-N CCOC(/C=C/c(cc1)ccc1[N+]([O-])=O)=N Chemical compound CCOC(/C=C/c(cc1)ccc1[N+]([O-])=O)=N DPRVNPIXZSEART-AIUUQRTRSA-N 0.000 description 1
- VAPXDUPUUGZUSO-UHFFFAOYSA-N CCOC(CCc(cc1)ccc1N)=N Chemical compound CCOC(CCc(cc1)ccc1N)=N VAPXDUPUUGZUSO-UHFFFAOYSA-N 0.000 description 1
- HYZFNHXSSHRQLU-UHFFFAOYSA-N CCc1nc(CCc(cc2)ccc2N)n[nH]1 Chemical compound CCc1nc(CCc(cc2)ccc2N)n[nH]1 HYZFNHXSSHRQLU-UHFFFAOYSA-N 0.000 description 1
- HHXQJALCZVMXQS-UHFFFAOYSA-N NC(CCc(cc1)ccc1[N+]([O-])=O)=O Chemical compound NC(CCc(cc1)ccc1[N+]([O-])=O)=O HHXQJALCZVMXQS-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention discloses a kind of triazole class compounds N ((5 (4 nitrobenzophenone) 2H 1; 2; the base of 4 triazole 3) methyl) amine of N propyl group the third 1 preparation method; it is initiation material with 3 (4 nitrobenzophenone) ethyl acrylates; target product 7 is obtained by reduction, acylation, imidization, cyclization, de- Boc, alkylated reaction, product of the present invention synthesizes diversified compound library as template small molecule.
Description
Technical field
The present invention relates to a kind of novel processing step of medicine intermediate, more particularly to a kind of triazole class compounds N- ((5-
(4- nitrobenzophenones) -2H-1,2,4- triazole -3- bases) methyl)-N- propyl group propyl- 1- amine preparation method.
Technical background
Compound N-((5- (4- nitrobenzophenones) -2H-1,2,4- triazole -3- bases) methyl)-N- propyl group propyl- 1- amine, structure
Formula is：
This compound N-((5- (4- nitrobenzophenones) -2H-1,2,4- triazole -3- bases) methyl)-N- propyl group propyl- 1- amine and phase
The derivative of pass has extensive use in pharmaceutical chemistry and organic synthesis.Current N- ((5- (4- nitrobenzophenones) -2H-1,2,4-
Triazole -3- bases) methyl)-N- propyl group propyl- 1- amine synthesis it is more difficult.Accordingly, it would be desirable to develop a raw material be easy to get, operation side
Just, easily controllable, the suitable synthetic method of overall yield is reacted.
The content of the invention
The invention discloses a kind of triazole compounds N- ((5- (4- nitrobenzophenones) -2H-1,2,4- triazole -3- bases) first
Base)-N- propyl group propyl- 1- amine preparation method, with 3- (3- bromophenyls) ethyl acrylate as initiation material, by reduction, it is acylated,
Imidization, cyclization, de- Boc, alkylated reaction obtain target product 7.Synthesis step is as follows：
(1), as initiation material, 2 are obtained by reduction reaction with 3- (4- nitrobenzophenones) ethyl acrylate,
(2) acylation reaction is carried out 2, obtains 3,
(3) carry out imidization 3 and obtain 4,
(4) carry out ring closure reaction 4 and obtain 5,
(5) de- Boc reactions are carried out 5 and obtain 6,
(6) it is alkylated reaction 6 and obtains 7；
One preferred embodiment in, reducing agent used by described reduction reaction prepare compound 2 is selected from hydroboration
Sodium；Reagent used by described acylation reaction prepare compound 3 is selected from ammoniacal liquor；The described institute of imidization prepare compound 4
Reagent is selected from triethyl group oxygen father-in-law's tetrafluoro boric acid；Reagent used by described ring closure reaction prepare compound 5 is selected from 2- (uncles N-
Butoxy carbonyl) ethyl acetate；Reagent used by described de- Boc reaction prepare compounds 6 is selected from hydrogen chloride；Described alkyl
Change the alkali used by reaction prepare compound 7 and be selected from potassium hydroxide.
One preferred embodiment in, solvent used by described reduction reaction prepare compound 2 is selected from methyl alcohol；It is described
Acylation reaction prepare compound 3 used by solvent be selected from water；Solvent choosing used by described imidization prepare compound 4
From tetrahydrofuran；Solvent used by described ring closure reaction prepare compound 5 is selected from isopropanol；It is prepared by described de- Boc reactions
Solvent used by compound 6 is selected from dichloromethane；Solvent used by described alkylated reaction prepare compound 7 is selected from toluene.
One preferred embodiment in, the reaction temperature used by described reduction reaction prepare compound 2 is room temperature；Institute
The temperature used by acylation reaction prepare compound 3 stated is 80 DEG C；Temperature used by described imidization prepare compound 4
It is the reflux temperature of solvent；Temperature used by described ring closure reaction prepare compound 5 is the reflux temperature of solvent；Described is de-
Temperature used by Boc reaction prepare compounds 6 is room temperature；Temperature used by described alkylated reaction prepare compound 7 is molten
The reflux temperature of agent.
The present invention relates to a kind of triazole compounds N- ((5- (4- nitrobenzophenones) -2H-1,2,4- triazole -3- bases) methyl) -
The preparation method of N- propyl group propyl- 1- amine, currently without other Patents documents report.
The present invention is further described by the following embodiment, and these descriptions are not present invention to be made into one
The restriction of step.It should be understood by those skilled in the art that the equivalent made to technical characteristic of the invention, or change accordingly
Enter, still fall within protection scope of the present invention.
Specific embodiment mode
Embodiment 1
(1) synthesis of 3- (4- nitrobenzophenones) ethyl propionate
21g 3- (4- nitrobenzophenones) ethyl acrylate is added in 220ml methyl alcohol, 17g sodium borohydrides, room temperature is added
Stirring 3 hours, cooling, concentration adds water and ethyl acetate, extraction point liquid to collect organic phase, dry, and concentration obtains 16g 3-
(3- bromophenyls) ethyl propionate.
(2) synthesis of 3- (4- nitrobenzophenones) propionamide
15g 3- (3- bromophenyls) ethyl propionate is added in 500ml ammoniacal liquor, 160ml water is added, 80 DEG C are heated to,
Stirring 10 hours, adds ethyl acetate extraction point liquid, collects organic phase, dries, and is concentrated to give 12g 3- (3- bromophenyls) propionyl
Amine.
(3) synthesis of 3- (4- nitrobenzophenones) third imino-ester
12g 3- (4- nitrobenzophenones) propionamide is added in 180ml tetrahydrofurans, 9g triethyl group oxygen father-in-law are slowly added to
Tetrafluoro boric acid, is heated to reflux stirring 6 hours, and cooling, filtering is collected filtrate, concentrated, and silica gel post separation obtains 9g 3- on residue
(4- nitrobenzophenones) third imino-ester.
(4) synthesis of tertbutyloxycarbonyl (5- (4- nitrobenzophenones) -2H-1,2,4- triazole -3- bases) methyl amine
9g 3- (3- bromophenyls) third imino-ester is added in 250ml isopropanols, 8g 2- (the tertiary fourth oxygen of N- is slowly added to
Base carbonyl) ethyl acetate and 15ml hydrazine hydrates, it is heated to reflux 24 hours, concentrate, add water and ethyl acetate, an extraction point liquid to receive
Collection organic phase, dries, concentration, isolated 11g tertbutyloxycarbonyls of silicagel column on residue (5- (4- nitrobenzophenones) -2H-1,2,
4- triazole -3- bases) methyl amine.
(5) synthesis of (5- (4- nitrobenzophenones) -2H-1,2,4- triazole -3- bases) methylamine
11g tertbutyloxycarbonyls (5- (4- nitrobenzophenones) -2H-1,2,4- triazole -3- bases) methyl amine is added to 130ml bis-
Chloromethanes, is passed through addition hydrogen chloride, stirs 12 hours, adds saturated sodium bicarbonate aqueous solution, extraction point liquid to collect organic phase,
Dry, be concentrated to give 5g (5- (4- nitrobenzophenones) -2H-1,2,4- triazole -3- bases) methylamine.
(6) synthesis of N- ((5- (4- nitrobenzophenones) -2H-1,2,4- triazole -3- bases) methyl)-N- propyl group propyl- 1- amine
5g (5- (3- bromophenyls) -2H-1,2,4- triazole -3- bases) methylamine is added in 100ml toluene, 4.5g is added
Potassium hydroxide and 14g 1- N-Propyl Bromides, are heated to reflux stirring 7 hours, add water and ethyl acetate, extraction point liquid to collect organic
Phase, dries, and concentration, residue ethyl alcohol recrystallization obtains 3.6g N- ((5- (4- nitrobenzophenones) -2H-1,2,4- triazole -3-
Base) methyl)-N- propyl group propyl- 1- amine.
Claims (5)
1. a kind of triazole class compounds N- ((5- (4- nitrobenzophenones) -2H-1,2,4- triazole -3- bases) methyl)-N- propyl group propyl-s 1-
The preparation method of amine, with 3- (4- nitrobenzophenones) ethyl acrylate as initiation material, by reduction, acylation, imidization, cyclization,
De- Boc, alkylated reaction obtain target product 7, and synthetic route is as follows：
2. method according to claim 1, it is characterized by described 6 steps reaction is,
(1), as initiation material, 2 are obtained by reduction reaction with 3- (4- nitrobenzophenones) ethyl acrylate,
(2) acylation reaction is carried out 2, obtains 3,
(3) carry out imidization 3 and obtain 4,
(4) carry out ring closure reaction 4 and obtain 5,
(5) de- Boc reactions are carried out 5 and obtain 6,
(6) it is alkylated reaction 6 and obtains 7；
3. method according to claim 1, it is characterised in that the reducing agent choosing used by described reduction reaction prepare compound 2
From sodium borohydride, Lithium Aluminium Hydride, potassium borohydride, iron powder, zinc powder, lithium borohydride, sodium cyanoborohydride, triacetoxy boron hydride
One or two mixture in sodium；Reagent used by described acylation reaction prepare compound 3 is selected from ammoniacal liquor；Described Asia
Reagent used by aminating reaction prepare compound 4 is selected from triethyl group oxygen father-in-law's tetrafluoro boric acid；Described ring closure reaction prepare compound 5
Reagent used is selected from 2- (N- tert-butoxycarbonyls) ethyl acetate；Reagent used by described de- Boc reaction prepare compounds 6
Selected from the mixture of one or more in hydrogen chloride, hydrochloric acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, p-methyl benzenesulfonic acid；Described alkane
Alkali used by glycosylation reaction prepare compound 7 is selected from lithium hydroxide, NaOH, potassium hydroxide, sodium carbonate, potassium carbonate, three second
The mixture of one or more in amine, pyridine.
4. method according to claim 1, it is characterised in that the solvent used by described reduction reaction prepare compound 2 is selected from
Methyl alcohol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene, meta-xylene, N,
One kind in dinethylformamide, DMAC N,N' dimethyl acetamide, triethylamine, pyridine, acetonitrile, acetic acid, trimethyl orthoformate or
Several mixtures；Solvent used by described acylation reaction prepare compound 3 be selected from methyl alcohol, ethanol, normal propyl alcohol, isopropanol,
Tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene, meta-xylene, N,N-dimethylformamide, N, N- dimethyl
The mixture of one or more in acetamide, acetonitrile, water；Solvent choosing used by described imidization prepare compound 4
From methyl alcohol, ethanol, normal propyl alcohol, isopropanol, acetonitrile, tetrahydrofuran, dioxane, dichloromethane, chloroform, toluene, adjacent two
One kind or several in toluene, paraxylene, meta-xylene, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, acetic acid, water
The mixture planted；Solvent used by described ring closure reaction prepare compound 5 is selected from methyl alcohol, ethanol, normal propyl alcohol, isopropanol, second
Nitrile, tetrahydrofuran, dioxane, dichloromethane, chloroform, toluene, ortho-xylene, paraxylene, meta-xylene, N, N- bis-
The mixture of one or more in NMF, DMAC N,N' dimethyl acetamide, acetic acid, water；It is prepared by described de- Boc reactions
Solvent used by compound 6 is selected from methyl alcohol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dioxane, dichloromethane, trichlorine
Methane, toluene, ortho-xylene, paraxylene, meta-xylene, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, acetonitrile,
The mixture of one or more in POCl3；Solvent used by described alkylated reaction prepare compound 7 be selected from methyl alcohol,
Ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dioxane, dichloromethane, chloroform, toluene, ortho-xylene, to diformazan
The mixture of one or more in benzene, meta-xylene, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, acetonitrile.
5. method according to claim 1, it is characterised in that the reaction temperature used by described reduction reaction prepare compound 2
It is the reflux temperature of 0 DEG C~solvent；Temperature used by described acylation reaction prepare compound 3 is the backflow temperature of 0 DEG C~solvent
Degree；Temperature used by described imidization prepare compound 4 is the reflux temperature of 0 DEG C~solvent；Described ring closure reaction
Temperature used by prepare compound 5 is the reflux temperature of 0 DEG C~solvent；Temperature used by described de- Boc reaction prepare compounds 6
Degree is the reflux temperature of 0 DEG C~solvent；Temperature used by described alkylated reaction prepare compound 7 is returning for 0 DEG C~solvent
Stream temperature.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104844528A (en) * | 2015-05-04 | 2015-08-19 | 湖南华腾制药有限公司 | Preparation method of triazole derivative |
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| CN104844528A (en) * | 2015-05-04 | 2015-08-19 | 湖南华腾制药有限公司 | Preparation method of triazole derivative |
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Application publication date: 20170613 |