CN101724001A - Method for synthesizing medicinal pyrimidine derivative - Google Patents
Method for synthesizing medicinal pyrimidine derivative Download PDFInfo
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- CN101724001A CN101724001A CN200810171750A CN200810171750A CN101724001A CN 101724001 A CN101724001 A CN 101724001A CN 200810171750 A CN200810171750 A CN 200810171750A CN 200810171750 A CN200810171750 A CN 200810171750A CN 101724001 A CN101724001 A CN 101724001A
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Abstract
The invention relates to a method for synthesizing a medicinal pyrimidine derivative. The method adopts a phosphamide compound as a reagent, uses 2'-O-methyl-uracil as a raw material, and performs reaction in an organic solvent in the presence of a catalyst. The mol ratio of a reactant to the reagent is between 1:1 and 1:50; the reaction time is 2 to 20 hours; the reaction temperature is between 50 and 200 DEG C; and the pressure is 1 to 10 MPa. The method has the advantages of simple operation, readily available raw materials, fewer reaction steps and high yield.
Description
Technical field:
The present invention relates to the synthetic of a class chemically modified Nucleotide, relate in particular to the method for the synthetic pyrimidine derivatives of a kind of catalysis.
Background technology:
Modification nucleotide is important medicine intermediate of a class and precursor, and has been widely used in treatment of diseases.For example, AZT, ddI, d4T etc. are used for the treatment of acquired immune deficiency syndrome (AIDS); 5 '-trifluormethyl-2 '-deoxyuridine is used for the treatment of herpetic keratitis; 5 '-iodo-1-(2-deoxy-2-fluoro-b-D-arabinofuranosyl) cytosine is used for the treatment of cytomegalovirus, simplexvirus, (Drug Design and Development such as the infection of Epstein-Barr virus etc., Povl Krogsgaard-Larsen and HansBundgaard, Eds, Harwood Academic Publishers, 1991, ch15).In addition, this compounds has also begun to be used to the antimycotic field of antibacterium.Explore new modification nucleotide route of synthesis and new nucleotide derivative will greatly enrich and expand the anti-infectives resource.
Summary of the invention:
The purpose of this invention is to provide low, the method for pyrimidine derivatives efficiently of a kind of reaction conditions gentleness, cost.Preferably, this compound is 5 '-Butylphosphate-2 '-O-methyl uridine-3 '-butyl phosphate.
For achieving the above object, technical scheme of the present invention is as follows: required the intermediate 2 '-O-methyl-Uridine of building-up reactions at first; (2-Cyanoethoxy) bis (N, N-diisopropylamino) phosphine; 2.2 (2-benzyloxy) bis (N, N-diisopropylamino) phosphine; 4-ter-butyldiphenylsiloxyl-1-butanol; 4-benzloxyl-butanol.Be reactant with 2 '-O-methyl-Uridine then, with 4-benzloxyl-butanol and 2.2 (2-benzyloxy) bis (N, N-diisopropylamino) phosphine is a reagent, synthetic 5 '-Butylphosphate-2 '-O-methyl uridine-3 '-butyl phosphate under tetrazole catalysis.
Specific implementation method:
Below by embodiment in detail the present invention is described in detail; But the present invention is not limited to following embodiment.
Embodiment 1.2 '-O-methyl-Uridine
2 '-O-methyl-Uridine compound can obtain by following reaction:
This reaction yield is 65%, through the NMR analysis verification exactness of product structure.
Embodiment 2. (2-Cyanoethoxy) bis (N, N-diisopropylamino) phosphine
(2-Cyanoethoxy) bis (N, N-diisopropylamino) phosphine can obtain by following reaction:
This reaction yield is 50%, through the exactness of NMR checking product structure.
Embodiment 3.2.2 (2-benzyloxy) bis (N, N-diisopropylamino) phosphine
2.2 (2-benzyloxy) bis (N, N-diisopropylamino) phosphine is obtained by following prepared in reaction:
This reaction yield is 70-90%
Embodiment 4.4-ter-butyldiphenylsiloxyl-1-butanol, 4-benzloxyl-butanol
4-ter-butyldiphenylsiloxyl-1-butanol, 4-benzloxyl-butanol can obtain by following reaction:
Exactness through its structure of NMR analysis verification.
Embodiment 5.4-benzloxyl-butanol
The synthetic of 4-benzloxyl-butanol carries out in the following manner:
Reaction product is a yellow oily, and reaction yield is 50%.
Embodiment 6.5 '-Butylphosphate-2 '-O-methyl uridine-3 '-butyl phosphate
5 '-Butylphosphate-2 '-O-methyl uridine-3 '-butyl phosphate obtains by following prepared in reaction:
This product warp
31P NMR and
1H NMR analysis verification, productive rate are 70%.Its purity is greater than 99%.
Claims (5)
1. the synthetic method of the synthetic pyrimidine nucleoside acid derivative of a catalysis, employings phosphamide compound is a reagent, is raw material with modification property pyrimidine, in the presence of catalyzer, reacts in organic solvent.The mol ratio of reactant and reagent is: 1: 1 to 1: 50; Reaction times is: 2～20 hours; Temperature of reaction is: 50～200 ℃; Pressure is: 1～10MPa.
2. the described modification pyrimidine of claim 1 is a uridylic; 2 '-O-6-Methyl Uracil; Thymus pyrimidine; 2 '-O-methyl thymus pyrimidine.
3. the described phosphamide compound of claim 1 is normal-butyl cyano ethyl-N, N-di-isopropyl phosphamide (n-butylcyanoethyl-N, N-diisopropyl phosphoramidite).
4. the described method of claim 1 is characterized in that, all organic solvents are one or more polarity or nonpolar inert solvent.
5. the described catalyzer of claim 1 is tetrazole or other short reaction reagent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810171750A CN101724001A (en) | 2008-10-24 | 2008-10-24 | Method for synthesizing medicinal pyrimidine derivative |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810171750A CN101724001A (en) | 2008-10-24 | 2008-10-24 | Method for synthesizing medicinal pyrimidine derivative |
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| CN101724001A true CN101724001A (en) | 2010-06-09 |
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| CN200810171750A Pending CN101724001A (en) | 2008-10-24 | 2008-10-24 | Method for synthesizing medicinal pyrimidine derivative |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103087096A (en) * | 2013-01-25 | 2013-05-08 | 苏州昊帆生物科技有限公司 | Preparation method of bis(diisopropylamine)(2-cyanoethoxy) phosphine |
| CN113476469A (en) * | 2017-03-10 | 2021-10-08 | 莱克伍德阿美达克斯股份有限公司 | Antimicrobial compounds, compositions and uses thereof |
| CN114369124A (en) * | 2022-01-21 | 2022-04-19 | 北京瑞博奥医药科技有限公司 | Preparation method of 2' -substituted pyrimidine nucleoside |
| US11795192B2 (en) | 2017-03-10 | 2023-10-24 | Lakewood Amedex, Inc. | Antimicrobial compounds, compositions, and uses thereof |
| US12030908B2 (en) | 2017-03-10 | 2024-07-09 | Lakewood Amedex, Inc. | Antimicrobial compounds, compositions, and uses thereof |
-
2008
- 2008-10-24 CN CN200810171750A patent/CN101724001A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103087096A (en) * | 2013-01-25 | 2013-05-08 | 苏州昊帆生物科技有限公司 | Preparation method of bis(diisopropylamine)(2-cyanoethoxy) phosphine |
| CN113476469A (en) * | 2017-03-10 | 2021-10-08 | 莱克伍德阿美达克斯股份有限公司 | Antimicrobial compounds, compositions and uses thereof |
| US11795192B2 (en) | 2017-03-10 | 2023-10-24 | Lakewood Amedex, Inc. | Antimicrobial compounds, compositions, and uses thereof |
| CN113476469B (en) * | 2017-03-10 | 2024-04-19 | 莱克伍德阿美达克斯股份有限公司 | Antimicrobial compounds, compositions and uses thereof |
| US12030908B2 (en) | 2017-03-10 | 2024-07-09 | Lakewood Amedex, Inc. | Antimicrobial compounds, compositions, and uses thereof |
| US12054509B2 (en) | 2017-03-10 | 2024-08-06 | Lakewood Amedex, Inc. | Antimicrobial compounds, compositions, and uses thereof |
| CN114369124A (en) * | 2022-01-21 | 2022-04-19 | 北京瑞博奥医药科技有限公司 | Preparation method of 2' -substituted pyrimidine nucleoside |
| CN114369124B (en) * | 2022-01-21 | 2024-03-26 | 北京瑞博奥医药科技有限公司 | Preparation method of 2' -substituted pyrimidine nucleoside |
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Application publication date: 20100609 |