Preparation method of fluorine-containing pyrimidine compound

A compound and pyrimidine technology, applied in the fields of materials and pharmaceutical intermediates synthesis, and natural products, can solve the problems of harsh reaction conditions, long reaction time, dangerous operation, etc., and achieve the effects of wide substrate range, high reaction efficiency and low cost.

Active Publication Date: 2017-06-13
上海旭东海普南通药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The existing problems in the method of synthesizing pyrimidine by metal-catalyzed multi-component reaction are: ① using substituted alkynes, amines and isocyanates as raw materials, using metal titanium, and preparing pyrimidine step by step at 100 °C
The disadvantages of this reaction are the use of toxic isocyanic raw materials, high temperature metal catalyst, step-by-step reaction, dangerous operation and environmental pollution.
The disadvantage of this reaction is that it needs to use two metal catalysts, the reaction conditions are harsh, and it also puts forward higher requirements for experimental equipment.
The disadvantage of this reaction is that it needs to use metal iridium complex catalyst, inert gas protection, tert-amyl alcohol as solvent, high temperature reflux is required, and the reaction time is longer

Method used

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  • Preparation method of fluorine-containing pyrimidine compound
  • Preparation method of fluorine-containing pyrimidine compound
  • Preparation method of fluorine-containing pyrimidine compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1 Ethyl-2-amino-4-methyl-6-perfluoropropylpyrimidine-5-carboxylate

[0038] 1. Put guanidine hydrochloride and sodium hydroxide into a 25mL round-bottomed flask, inject 3mL of acetonitrile solvent, pre-treat and remove acid to obtain free guanidine. Then, ethyl acetoacetate and perfluoroiodobutane were added successively at room temperature. The reaction was carried out under room light and room temperature for 6 h, and the end point of the reaction was monitored by TLC, and the reaction was stopped to obtain a mixture.

[0039] In molar ratio, ethyl acetoacetate: perfluoroiodobutane: guanidine hydrochloride: sodium hydroxide=1.0:1.1:1.1:4.1;

[0040] 2. The mixture was extracted 3 times with water, the organic phases were combined, and the organic solvent was distilled off under reduced pressure to obtain a crude product;

[0041] 3. Pass the crude product through silica gel column chromatography, and elute with an eluent (petroleum ether: ethyl acetate = 30:...

Embodiment 2

[0047] Example 2 Methyl-2-amino-4-ethyl-6-perfluoropropylpyrimidine-5-carboxylate

[0048] 1. Put guanidine hydrochloride and sodium hydroxide into a 25mL round-bottomed flask, inject 3mL of acetonitrile solvent, pre-treat and remove acid to obtain free guanidine. Then, methyl 3-oxopentanoate and perfluoroiodobutane were added successively at room temperature. The reaction was carried out under room light and room temperature for 7 hours, the end point of the reaction was monitored by TLC, and the reaction was stopped to obtain a mixture.

[0049] In molar ratio, methyl 3-oxopentanoate: perfluoroiodobutane: guanidine hydrochloride: sodium hydroxide=1.0:1.1:1.1:4.1;

[0050] The mixture was extracted 3 times with water, the organic phases were combined, and the organic solvent was distilled off under reduced pressure to obtain a crude product;

[0051]2. The crude product is eluted by silica gel column chromatography with an eluent (petroleum ether: ethyl acetate = 30:1 (v:v)...

Embodiment 3

[0057] Example 3 Ethyl-2-amino-4-perfluoropropyl-6-phenylpyrimidine-5-carboxylate

[0058] 1. Put guanidine hydrochloride and sodium hydroxide into a 25mL round-bottomed flask, inject 3mL of acetonitrile solvent, pre-treat and remove acid to obtain free guanidine. Then, ethyl benzoylacetate and perfluoroiodobutane were added sequentially at room temperature. The reaction was carried out under room light and room temperature for 5 h, the end point of the reaction was monitored by TLC, and the reaction was stopped to obtain a mixture.

[0059] In molar ratio, ethyl benzoyl acetate: perfluoroiodobutane: guanidine hydrochloride: sodium hydroxide=1.0:1.1:1.1:4.1;

[0060] 2. The mixture was extracted 3 times with water, the organic phases were combined, and the organic solvent was distilled off under reduced pressure to obtain a crude product;

[0061] 3. Pass the crude product through silica gel column chromatography, and elute with an eluent (petroleum ether: ethyl acetate = 30...

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Abstract

The invention relates to a preparation method of a fluorine-containing pyrimidine compound. The fluorine-containing pyrimidine compound has a structure in a general formula (IV). The preparation method comprises the steps: adding alkali and guanidine hydrochloride or amidine to a reaction flask, injecting an organic solvent, carrying out pretreatment, neutralization and deacidification to obtain free guanidine or amidine; successively adding a methylene compound and perfluoroalkyl iodide at room temperature and under illumination, monitoring a reaction end point through a TLC; extracting with water, collecting an organic phase and carrying out vacuum distillation to remove a solvent; and finally obtaining a product through silica-gel column chromatography. The synthetic route has the advantages of being cheap and available in substrate, wide in range, free of transition metal catalysis, mild in conditions, safe in reaction route and simple in operation, and the energy consumption is reduced. The formula is as shown in the description.

Description

technical field [0001] The invention relates to the field of synthesis of natural products, materials and pharmaceutical intermediates, in particular to the promotion of single-electron transfer between electron-donor-acceptor (EDA) complexes through visible light, and further "one-pot" three-component synthesis of perfluoroalkylpyrimidines resolve resolution. Background technique [0002] Pyrimidines are structural units of many natural products with biological and pharmaceutical activities, and have important applications in medicine, pesticides and dyes. At the same time, it can also be used in optoelectronic materials, such as OLEDs as electron transport materials. Therefore, its synthetic methods have received extensive attention, and some representative methods include: 1) Condensation of amidines with carbonyl compounds under basic conditions. 2) Using palladium and copper metal co-catalysis, "one pot two steps" method to construct pyrimidine. 3) Using metal iridiu...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): C07D239/42C07D239/28C07D239/30C07D239/26
CPCC07D239/26C07D239/28C07D239/30C07D239/42
Inventor梁福顺汪锐韩正波苏忠民
Owner上海旭东海普南通药业有限公司