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A method for preparing uracil and thymine derivatives

A technology of thymine and uracil, which is applied in the field of efficient preparation of uracil and thymine derivatives, achieving the effects of convenient purification, high step economy, efficient and diversified methods

Active Publication Date: 2022-03-04
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are many synthesis methods of pyrimidine and thymine derivatives [A.V.Dudnik, A.S.Gulevich, N.Chernyak, V. Gevorgyan, Chem.Rev.2013, 113, 3084], but starting from simple raw materials, efficient preparation of pyrimidine and thymine There are few reports on the synthetic methods of thymine derivatives

Method used

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  • A method for preparing uracil and thymine derivatives
  • A method for preparing uracil and thymine derivatives
  • A method for preparing uracil and thymine derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1: Preparation of 1,3-dibenzyl-5-methylpyrimidine-2,4(1H,3H)-dione-6-d

[0038]

[0039] Under the protection of an inert gas, add Pd(OAc) to a dry 4.0mL reaction bottle equipped with a magnetic stir bar 2(1.1mg, 5mol%), NBE-CONHMe (7.6mg, 50mol%), 1,3-dibenzyl-6-iodopyrimidine-2,4(1H,3H)-dione (0.12 mmol, 1.2equiv) , methyl p-toluenesulfonate (0.15mmol, 1.5equiv), DCO 2 Na (0.1 mmol, 1.0 equiv), potassium carbonate (0.25 mmol, 2.5 equiv) and dried 1,4-dioxane (1.0 mL). The above reaction solution was placed on a heating block preheated to 130° C. and stirred for 48 hours. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the mixture was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (colorless oil, 52%, 80% D). 1 H NMR (400MHz, CDC...

Embodiment 2

[0040] Example 2: Preparation of 1,3-dibenzyl-5-methyl-6-phenylpyrimidine-2,4(1H,3H)-dione

[0041]

[0042] Under the protection of an inert gas, add Pd(OAc) to a dry 4.0mL reaction bottle equipped with a magnetic stir bar 2 (1.1mg, 5mol%), NBE-CONHMe (7.6mg, 50mol%), 1,3-dibenzyl-6-iodopyrimidine-2,4(1H,3H)-dione (0.12 mmol, 1.2 equiv) , methyl p-toluenesulfonate (0.15 mmol, 1.5 equiv), PhBPin (0.1 mmol, 1.0 equiv), potassium carbonate (0.25 mmol, 2.5 equiv) and dried 1,4-dioxane (1.0 mL). The above reaction solution was placed on a heating block preheated to 130° C. and stirred for 48 hours. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the mixture was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (colorless oil, 52%) . 1 H NMR (400MHz, CDC...

Embodiment 3

[0043] Example 3: Preparation of (E)-1,3-dibenzyl-5-methyl-6-styrylpyrimidine-2,4(1H,3H)-dione

[0044]

[0045] Under the protection of an inert gas, add Pd(OAc) to a dry 4.0mL reaction bottle equipped with a magnetic stir bar 2 (1.1mg, 5mol%), NBE-CONHMe (7.6mg, 50mol%), 1,3-dibenzyl-6-iodopyrimidine-2,4(1H,3H)-dione (0.12 mmol, 1.2equiv) , methyl p-toluenesulfonate (0.15 mmol, 1.5 equiv), styrene (0.1 mmol, 1.0 equiv), potassium carbonate (0.25 mmol, 2.5 equiv) and dried 1,4-dioxane (1.0 mL). The above reaction solution was placed on a heating block preheated to 130° C. and stirred for 48 hours. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature. The mixture was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (colorless oil, 47%) . 1 H NMR (400MHz,...

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Abstract

The invention provides a method for efficiently and diversifying the synthesis of uracil and thymine derivatives. In this method, iodouracil and thymine compounds, electrophiles (halogenated alkanes or brominated aromatic compounds), nucleophiles (alkenes, alkynes, borates, etc.), palladium catalysts, norbornene derivatized Dissolve the substance and alkali (potassium carbonate) together in an organic solvent (1,4-dioxane or ethylene glycol dimethyl ether), then stir and react at 50-150°C, and separate and purify after the reaction, which can be efficient and economical , Green synthesis of polysubstituted uracil and thymine compounds. The method has mild conditions, good substrate universality and high yield, and the prepared 2-pyridones and uracils are widely used in the fields of medicinal chemistry and organic chemistry. In addition, a method for synthesizing key intermediates of anti-HIV drugs is also provided, which improves step economy.

Description

technical field [0001] The invention relates to a method for efficiently preparing uracil and thymine derivatives, belonging to the field of organic synthesis. Background technique [0002] Uracil and thymine are important structural units widely present in many biologically active natural products and pharmaceutical molecular structures [a) H.J.Jessen, K.Gademann, Nat.Prod.Rep.2010, 27, 1168; b) Z.Lv, C.Sheng, T.Wang, Y.Zhang, J.Liu, J.Feng, H.Sun, H.Zhong, C.Niu, K.Li, J.Med.Chem.2010, 53,2660. At present, there are many synthesis methods of pyrimidine and thymine derivatives [A.V.Dudnik, A.S.Gulevich, N.Chernyak, V. Gevorgyan, Chem.Rev.2013, 113, 3084], but starting from simple raw materials, efficient preparation of pyrimidine and thymine There are few reports on the synthetic methods of thymine derivatives. Contents of the invention [0003] In order to solve the problems in the prior art, the invention provides a method for efficiently synthesizing uracil and thym...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/54C07F7/10
CPCC07D239/54C07F7/083C07F7/0812C07B2200/05
Inventor 周强辉尚勇吴承贵
Owner WUHAN UNIV
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