CN104926799A - Method for synthesizing piribedil - Google Patents
Method for synthesizing piribedil Download PDFInfo
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- CN104926799A CN104926799A CN201510181730.0A CN201510181730A CN104926799A CN 104926799 A CN104926799 A CN 104926799A CN 201510181730 A CN201510181730 A CN 201510181730A CN 104926799 A CN104926799 A CN 104926799A
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- piribedil
- piperazine
- synthesis
- pyrimidyl
- ratio
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- UXSACZMAAVIJSD-UHFFFAOYSA-N CCC1=C(C=C)OCO1 Chemical compound CCC1=C(C=C)OCO1 UXSACZMAAVIJSD-UHFFFAOYSA-N 0.000 description 1
- QIZCQMPNXSZSNU-FMIVXFBMSA-N CCN(CCNC)/C(/N=C)=N/C=C Chemical compound CCN(CCNC)/C(/N=C)=N/C=C QIZCQMPNXSZSNU-FMIVXFBMSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
The invention relates to a method for synthesizing piribedil represented by a following formula. According to the method, stable, cheap and easy-to-obtain piperic acid and 1-(2-pyrimidinyl)piperazine are adopted as initial raw materials; a nonmetal boron compound is adopted as a catalyst; an organosilane compound is adopted as a reducing agent; and the needed product is synthesized with a one-step method through a reductive coupling process. The method provided by the invention is simple and is easy to operate. The raw materials have wide sources and low costs. The synthesis does not require a metal catalyst, such that metal residue in drugs is avoided. The method is safe and environment-friendly, and meets the requirements of green chemistry.
Description
Technical field
The present invention relates to pharmaceutical chemistry synthesis field, be specifically related to a kind of method of synthesis Piribedil (Piribedil).
Background technology
The chemistry of Piribedil is called: 2-[4-(1,3-benzodioxole-5-ylmethyl) piperazine-1-base] pyrimidine, and structure is expressed from the next:
Piribedil is applicable to Parkinson's disease (Parkinson ' s disease) patient, is a kind of Dopaminergic Agents, and it by stimulating brain nigrostriatum postsynaptic D2 acceptor and middle Cerebral cortex, and provides effective Dopamine HCL effect.
CN101735201 take piperonyl cyclonene as raw material, reacts, obtain piperonyl chlorine with paraformaldehyde and concentrated hydrochloric acid, is then being obtained by reacting target product (route 1) with 1-(2-pyrimidyl) piperazine:
American chemical periodical J.Am.Chem.Soc.2009,131 (5), 1766-1774 report with 1-(2-pyrimidyl) piperazine and piperitol for raw material, utilize [Ru (p-cymene) Cl
2]
2catalysis, single stage method prepares Piribedil (route 2):
But, there is route longer (route 1 described above) in these methods, complicated operation.Simultaneously, although above-mentioned route 2 achieves one-step synthesis, but its raw material piperitol is expensive, and need to use noble ruthenium to participate in catalysis, ruthenium catalyst price is higher, in this synthetic method, catalyst levels is large, it is higher that this makes not only to synthesize cost, and due to the participation of metal catalyst, metal can be caused to remain in synthesized medicine, cause obtained medicine to there is unsafe problem, the use of precious metal simultaneously also can make whole building-up process not environmentally, does not meet current Green Chemistry requirement.
Summary of the invention
In order to solve above-mentioned part or all of problem of the prior art, the invention provides a kind of method of novel synthesis Piribedil.
On the one hand, the present invention relates to a kind of method of synthesizing Piribedil, described method comprises:
By 1-(2-pyrimidyl) piperazine of formula (I)
With the piperinic acid of formula (II)
In organic solvent, take organic silane compound as reductive agent, be that catalyzer issues raw reductive coupling reaction at nonmetal boron compound, and obtain the Piribedil product of formula (III),
In a preferred embodiment, the ratio of the molar weight of described piperinic acid and described 1-(2-pyrimidyl) piperazine is 1.0-2.5.
In a preferred embodiment, described nonmetal boron compound is at least one in triethyl-boron, three (pentafluorophenyl group) boron.
In a preferred embodiment, described organic silane compound is at least one in diphenyl silane, diethylsilane, phenyl silane.
In a preferred embodiment, described organic solvent is at least one in toluene, m-xylene, sym-trimethylbenzene, Isosorbide-5-Nitrae-dioxane, n-butyl ether.
In a preferred embodiment, the ratio of the described nonmetal boron compound of use and the molar weight of described 1-(2-pyrimidyl) piperazine is 0.005-0.02.
In a preferred embodiment, the ratio of the described organic silane compound of use and the molar weight of described 1-(2-pyrimidyl) piperazine is 3.0-5.0.
In a preferred embodiment, the ratio of the volume (milliliter) of described organic solvent and the molar weight consumption (mmole) of described 1-(2-pyrimidyl) piperazine, that is: the mole dosage of volume/1-(2-pyrimidyl) piperazine of organic solvent is 2.0-5.0.
In a preferred embodiment, the temperature of described reductive coupling reaction is 80 DEG C-150 DEG C.
In a preferred embodiment, the time of described reductive coupling reaction is 15h-25h.
The present invention by with 1-(2-pyrimidyl) piperazine and piperinic acid for starting raw material, with nonmetal boron compound for catalyzer, use organic silane compound is reductive agent, by the process of reductive coupling, and the Piribedil product that one-step synthesis method is required.Simple synthetic method of the present invention, easy to operate, raw material is easy to get, and cost is lower.Meanwhile, in synthetic method of the present invention, do not need metal catalyst to participate in, avoid metal remaining in medicine, safety, environmental protection, meet Green Chemistry requirement.
Accompanying drawing explanation
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of Piribedil prepared by the embodiment of the present invention 1;
Fig. 2 is the carbon-13 nmr spectra figure of Piribedil prepared by the embodiment of the present invention 1.
Embodiment
The present invention by with 1-(2-pyrimidyl) piperazine and piperinic acid for starting raw material, with nonmetal boron compound for catalyzer, use organic silane compound is reductive agent, by the process of reductive coupling, and the Piribedil product that one-step synthesis method is required.
More specifically, synthesis Piribedil method of the present invention comprises: by 1-(2-pyrimidyl) piperazine of formula (I)
with the piperinic acid of formula (II)
in organic solvent, take organic silane compound as reductive agent, be that catalyzer issues raw reductive coupling reaction at nonmetal boron compound, and obtain the Piribedil of formula (III)
Preferably, the ratio of the molar weight consumption of the molar weight consumption of the piperinic acid of use and 1-(2-pyrimidyl) piperazine is 1.0-2.5, is more preferably 2.0.
Preferably, the nonmetal boron compound of use is triethyl-boron, at least one of three (pentafluorophenyl group) boron, is more preferably three (pentafluorophenyl group) boron.
Preferably, the organic silane compound of use is diphenyl silane, at least one in diethylsilane, phenyl silane, is more preferably phenyl silane.
Preferably, the organic solvent of use is toluene, m-xylene, sym-trimethylbenzene, Isosorbide-5-Nitrae-dioxane, at least one in n-butyl ether, be more preferably n-butyl ether.
Preferably, the ratio of the molar weight of the nonmetal boron compound of use and 1-(2-pyrimidyl) piperazine is 0.005-0.02, is more preferably 0.01.
Preferably, the ratio of the molar weight of the organic silane compound of use and 1-(2-pyrimidyl) piperazine is 3.0-5.0, is more preferably 4.0.
Preferably, the volume (milliliter) of organic solvent used and the ratio of the molar weight consumption (mmole) of described 1-(2-pyrimidyl) piperazine, the ratio of the mmole number of the volume milliliter number of the organic solvent such as used and 1-(2-pyrimidyl) piperazine is 2.0,3.0,4.0 or 5.0, is more preferably 3.0.
Preferably, the temperature of described reductive coupling reaction is 80 DEG C-150 DEG C, is more preferably 140 DEG C.
Preferably, the time of described reductive coupling reaction is 15h-25h, is more preferably 22h.
In order to illustrate the present invention further; below in conjunction with embodiment, the preferred embodiment of the invention is described; but be to be understood that; these describe just to further illustrate the features and advantages of the present invention; instead of limiting to the claimed invention; those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.The experimental technique of unreceipted actual conditions in the following example, the usually conveniently conditioned disjunction condition of advising according to manufacturer.
Unless otherwise defined, all specialties used in literary composition and scientific words and one skilled in the art the same meaning be familiar with.In addition, any method similar or impartial to described content and material all can be applicable in the inventive method.The use that better implementation method described in literary composition and material only present a demonstration.
The medicine used for the synthesis of Piribedil in the following embodiment of the present invention is bought in following Reagent Company respectively:
Triethyl-boron (C
6h
15b, 99%), 1-(2-pyrimidyl) piperazine (C
12h
13n, 99.0%), piperinic acid (C
10h
9f
3o
2, 98.0%), diethylsilane (Et
2siH
2, 98+%), diphenyl silane (Ph
2siH
2, 99%), phenyl silane (C
6h
8si, 98%) all buy from lark prestige chemical reagents corporation.
Ethyl acetate (99.5%), sodium hydroxide (NaOH, 96.0%), anhydrous sodium sulphate (Na
2sO
4, 99.0%), toluene (C
7h
8, 99.5%) buy from traditional Chinese medicines chemical reagents corporation.
M-xylene (C
8h
10, 99.0%), sym-trimethylbenzene (C
9h
12, 97.0%), three (pentafluorophenyl group) boron (B (C
6f
5)
3, 97+%) all buy from TCI company.
1h-NMR and
13c-NMR spectrogram all obtains in Bruker Avance 400 nuclear magnetic resonance analyser.
Embodiment
Embodiment 1
In Schlenk reaction tubes (Beijing Xin Weier glassware company limited of 10mL, F891410 reaction tubes, capacity 10mL, ground 14/20) in add 0.005mmol tri-(pentafluorophenyl group) boron, use argon replaces inner air tube, then under argon atmosphere, add 1.5mL n-butyl ether and 2.0mmol phenyl silane and stir (using IKA magnetic stirring apparatus, RCT basic model, stirring velocity 500 revs/min).Then 0.5mmol 1-(2-pyrimidyl) piperazine and 1.0mmol piperinic acid is added.Heat 20h at 100 DEG C after, be cooled to room temperature.With sodium hydroxide solution (3M; 3mL) cancellation, add ethyl acetate (3mL), after stirred at ambient temperature 3h, extraction into ethyl acetate (2mL x 3), organic phase anhydrous sodium sulfate drying, filter, organic phase is by Rotary Evaporators (Bu Qi company limited of Switzerland, BUCHI Rotary Evaporators R-3) concentrated, then through chromatography column (Beijing Xin Weier glassware company limited, C383040C tool sand plate storage ball chromatography column, 35/20, φ 30mm, effectively long: 500ml) chromatographic separation obtains White crystalline product, productive rate 41%.
Products therefrom is carried out proton nmr spectra
1h-NMR (400MHz, CDCl
3) and carbon-13 nmr spectra
13c-NMR (101MHz, CDCl
3) analyze, the spectrogram obtained is respectively as shown in Figure 1-2.Confirm that products therefrom is 2-[4-(1,3-benzodioxole-5-ylmethyl) piperazine-1-base] pyrimidine, i.e. Piribedil thus.
1H NMR(400MHz,CDCl
3)δ8.28(d,J=4.7Hz,2H),6.88(s,1H),6.75(s,2H),6.45(t,J=4.7Hz,1H),5.94(s,2H),3.81(t,4H),3.44(s,2H),2.47(t,4H).
13C NMR(101MHz,CDCl
3)δ161.64,157.71,147.69,146.69,131.79,122.29,109.74,109.54,107.91,100.93,62.87,52.82,43.67.
Embodiment 2
Carry out with the program identical with embodiment 1, after just reaction mixture being heated 22h at 120 DEG C, be cooled to room temperature.Obtain separation through identical aftertreatment and obtain White crystalline product, productive rate 72%.
Products therefrom is carried out proton nmr spectra and carbon-13 nmr spectra analysis, confirmation products therefrom is 2-[4-(1,3-benzodioxole-5-ylmethyl) piperazine-1-base] pyrimidine, i.e. Piribedil.
Embodiment 3
Carry out with the program identical with embodiment 1, after just reaction mixture being heated 22h at 140 DEG C, be cooled to room temperature.Obtain separation through identical aftertreatment and obtain White crystalline product, productive rate 83%.
Products therefrom is carried out proton nmr spectra and carbon-13 nmr spectra analysis, confirmation products therefrom is 2-[4-(1,3-benzodioxole-5-ylmethyl) piperazine-1-base] pyrimidine, i.e. Piribedil.
Embodiment 4
Carry out with the program identical with embodiment 1, after just reaction mixture being heated 24h at 140 DEG C, be cooled to room temperature.Obtain separation through identical aftertreatment and obtain White crystalline product, productive rate 85%.
Products therefrom is carried out proton nmr spectra and carbon-13 nmr spectra analysis, confirmation products therefrom is 2-[4-(1,3-benzodioxole-5-ylmethyl) piperazine-1-base] pyrimidine, i.e. Piribedil.
Embodiment 5
Carry out with the program identical with embodiment 3, just change the 1.5mL n-butyl ether being wherein used as organic solvent into 2.0mL toluene, after reaction mixture is heated 22h at 140 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 64%.
Through proton nmr spectra and carbon-13 nmr spectra analysis, confirmation products therefrom is 2-[4-(1,3-benzodioxole-5-ylmethyl) piperazine-1-base] pyrimidine, i.e. Piribedil.
Embodiment 6
Carry out with the program identical with embodiment 3, just change the 1.5mL n-butyl ether being wherein used as organic solvent into 1.0mL m-xylene, after reaction mixture is heated 22h at 140 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 61%.
Through proton nmr spectra and carbon-13 nmr spectra analysis, confirmation products therefrom is 2-[4-(1,3-benzodioxole-5-ylmethyl) piperazine-1-base] pyrimidine, i.e. Piribedil.
Embodiment 7
Carry out with the program identical with embodiment 3, just change the 1.5mL n-butyl ether being wherein used as organic solvent into 1.0mL sym-trimethylbenzene, after reaction mixture is heated 24h at 120 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 65%.
Through proton nmr spectra and carbon-13 nmr spectra analysis, confirmation products therefrom is 2-[4-(1,3-benzodioxole-5-ylmethyl) piperazine-1-base] pyrimidine, i.e. Piribedil.
Embodiment 8
Carry out with the program identical with embodiment 3, just change the 1.5mL n-butyl ether being wherein used as organic solvent into 3.0mL Isosorbide-5-Nitrae-dioxane, after reaction mixture is heated 24h at 140 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 78%.
Through proton nmr spectra and carbon-13 nmr spectra analysis, confirmation products therefrom is 2-[4-(1,3-benzodioxole-5-ylmethyl) piperazine-1-base] pyrimidine, i.e. Piribedil.
Embodiment 9
Carry out with the program identical with embodiment 3, just the 2.0mmol phenyl silane being wherein used as reductive agent is replaced with 2.5mmol diphenyl silane, after reaction mixture is heated 22h at 140 DEG C, be cooled to room temperature.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 71%.
Through proton nmr spectra and carbon-13 nmr spectra analysis, confirmation products therefrom is 2-[4-(1,3-benzodioxole-5-ylmethyl) piperazine-1-base] pyrimidine, i.e. Piribedil.
Embodiment 10
Carry out with the program identical with embodiment 3, the 1.0mmol piperinic acid just added changes 0.75mmol piperinic acid into, is cooled to room temperature after reaction mixture is heated 22h at 140 DEG C.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 58%.
Through proton nmr spectra and carbon-13 nmr spectra analysis, confirmation products therefrom is 2-[4-(1,3-benzodioxole-5-ylmethyl) piperazine-1-base] pyrimidine, i.e. Piribedil.
Embodiment 11
Carry out with the program identical with embodiment 3, the 1.0mmol piperinic acid just added changes 1.25mmol piperinic acid into, is cooled to room temperature after reaction mixture is heated 22h at 140 DEG C.Be separated through identical aftertreatment and obtain White crystalline product, productive rate 81%.
Through proton nmr spectra and carbon-13 nmr spectra analysis, confirmation products therefrom is 2-[4-(1,3-benzodioxole-5-ylmethyl) piperazine-1-base] pyrimidine, i.e. Piribedil.
Above a kind of method of synthesizing Piribedil provided by the present invention is described in detail.Apply specific case herein to set forth the principle of invention and embodiment, the explanation of above embodiment just understands method of the present invention and core concept thereof for helping.It should be pointed out that for those skilled in the art, under or else departing from the prerequisite of the principle of the invention, can also carry out some improvement and modification to the present invention, these improve and modify and also fall in the protection domain of the claims in the present invention.
Claims (10)
1. synthesize a method for Piribedil, described method comprises:
By 1-(2-pyrimidyl) piperazine of formula (I)
With the piperinic acid of formula (II)
In organic solvent, take organic silane compound as reductive agent, be that catalyzer issues raw reductive coupling reaction at nonmetal boron compound, and obtain the Piribedil product of formula (III),
2. the method for synthesis Piribedil according to claim 1, is characterized in that, the ratio of the molar weight of the described piperinic acid of use and described 1-(2-pyrimidyl) piperazine is 1.0-2.5.
3. the method for synthesis Piribedil according to claim 1, is characterized in that, described nonmetal boron compound is at least one in triethyl-boron, three (pentafluorophenyl group) boron.
4. the method for synthesis Piribedil according to claim 1, is characterized in that, described organic silane compound is at least one in diphenyl silane, diethylsilane, phenyl silane.
5. the method for synthesis Piribedil according to claim 1, is characterized in that, described organic solvent is at least one in toluene, m-xylene, sym-trimethylbenzene, Isosorbide-5-Nitrae-dioxane, n-butyl ether.
6. the method for synthesis Piribedil according to claim 3, is characterized in that, the ratio of the molar weight of the described nonmetal boron compound of use and described 1-(2-pyrimidyl) piperazine is 0.005-0.02.
7. the method for synthesis Piribedil according to claim 4, is characterized in that, the ratio of the molar weight of described organic silane compound and described 1-(2-pyrimidyl) piperazine is 3.0-5.0.
8. the method for synthesis Piribedil according to claim 5, is characterized in that, the ratio of the mmole quantity of the volume ml quantity of described organic solvent and described 1-(2-pyrimidyl) piperazine is 2.0-5.0.
9. the method for synthesis Piribedil according to any one of claim 1 to 8, is characterized in that, the temperature of described reductive coupling reaction is 80 DEG C-150 DEG C.
10. the method for synthesis Piribedil according to any one of claim 1 to 8, is characterized in that, the time of described reductive coupling reaction is 15h-25h.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106432212A (en) * | 2016-09-21 | 2017-02-22 | 苏州弘森药业股份有限公司 | Synthetic method of piribedil |
CN108409818A (en) * | 2018-05-16 | 2018-08-17 | 新乡拓新药业股份有限公司 | A kind of method of synthesizing cytimidine nucleosides |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008035381A2 (en) * | 2006-09-22 | 2008-03-27 | Ind-Swift Laboratories Limited | Process for the preparation of amine derivatives as calcimimetics |
CN101735201A (en) * | 2009-12-17 | 2010-06-16 | 宁夏康亚药业有限公司 | Preparation method of piribedil |
CN103706395A (en) * | 2013-12-23 | 2014-04-09 | 南京工业大学 | Nano ruthenium catalyst and application thereof |
-
2015
- 2015-04-16 CN CN201510181730.0A patent/CN104926799B/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008035381A2 (en) * | 2006-09-22 | 2008-03-27 | Ind-Swift Laboratories Limited | Process for the preparation of amine derivatives as calcimimetics |
CN101735201A (en) * | 2009-12-17 | 2010-06-16 | 宁夏康亚药业有限公司 | Preparation method of piribedil |
CN103706395A (en) * | 2013-12-23 | 2014-04-09 | 南京工业大学 | Nano ruthenium catalyst and application thereof |
Non-Patent Citations (4)
Title |
---|
IVAN SORRIBES,等: ""Direct Catalytic N‑Alkylation of Amines with Carboxylic Acids"", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
MATTHEW A. J. DUNCTON,等: ""Parallel synthesis of N-arylpiperazines using polymer-assisted reactions"", 《TETRAHEDRON LETTERS》 * |
XINJIANG CUI,等: ""Development of a General Non-Noble Metal Catalyst for the Benign Amination of Alcohols with Amines and Ammonia"", 《CHEM. EUR. J.》 * |
王绍杰,等: "《吡贝地尔的合成》", 《中国医药工业杂志》 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106432212A (en) * | 2016-09-21 | 2017-02-22 | 苏州弘森药业股份有限公司 | Synthetic method of piribedil |
CN106432212B (en) * | 2016-09-21 | 2019-01-11 | 苏州弘森药业股份有限公司 | A method of synthesis piribedil |
CN108409818A (en) * | 2018-05-16 | 2018-08-17 | 新乡拓新药业股份有限公司 | A kind of method of synthesizing cytimidine nucleosides |
CN108409818B (en) * | 2018-05-16 | 2020-09-11 | 新乡拓新药业股份有限公司 | Method for synthesizing cytosine nucleoside |
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