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Preparation method of halogenated uracil compounds

A compound, uracil technology, applied in the field of preparation of halogenated uracil compounds, can solve the problems of high toxicity of chlorinating reagents or solvents, high reaction temperature, low yield and the like, and achieves easy judgment and control, reflux reaction temperature Low, high yield effect

Active Publication Date: 2021-05-07
SHANGHAI INST OF PHARMA IND CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The technical problem to be solved by the present invention is to overcome the defects of the existing 2,4-dichloro-5-bromopyrimidine preparation method that the chlorination reagent or solvent is highly toxic, the yield is low, and the reaction temperature is high. A kind of preparation method of halouracil compound

Method used

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  • Preparation method of halogenated uracil compounds
  • Preparation method of halogenated uracil compounds
  • Preparation method of halogenated uracil compounds

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Experimental program
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Effect test

Embodiment 1

[0039] 5-bromouracil (6.0g, 31.4mmol) and PCl 5 (16.4 g, 78.5 mmol) were mixed in a reaction flask, 1,2-dichloroethane (50 mL) was added, and the reaction mixture was heated to reflux. During the reaction, the mixture changed from a suspension state to a light yellow clear solution, at this time, TLC showed that the reaction of the raw materials was complete, and the mixture was cooled to room temperature. The reaction mixture was slowly poured into stirred ice water, stirred for 1 h, added DCM (3×50 mL) for extraction, the organic layer was added anhydrous MgSO 4 After drying, the solvent was evaporated to obtain a light yellow transparent liquid. The silica gel column was further purified to obtain a colorless transparent liquid, that is, compound 2 (yield 99%, purity 97.5%).

Embodiment 2

[0041] 5-bromouracil (6.0g, 31.4mmol) and PCl 5 (19.68g, 94.2mmol) mixed in the reaction flask, add SOCl 2 (50 mL), the reaction mixture was heated to reflux. During the reaction, the mixture changed from a suspension state to a light yellow clear solution, at this time, TLC showed that the reaction of the raw materials was complete, and the mixture was cooled to room temperature. The reaction mixture was slowly poured into stirred ice water, stirred for 1 h, added DCM (3×50 mL) for extraction, the organic layer was added anhydrous MgSO 4 After drying, the solvent was evaporated to obtain a light yellow transparent liquid. The silica gel column was further purified to obtain a colorless transparent liquid, that is, compound 2 (yield 99%, purity 97.2%).

Embodiment 3

[0043] 5-bromouracil (6.0g, 31.4mmol) and PCl 5(16.4 g, 78.5 mmol) were mixed in a reaction flask, carbon tetrachloride (50 mL) was added, and the reaction mixture was heated to reflux. During the reaction, the mixture changed from a suspension state to a light yellow clear solution, at this time, TLC showed that the reaction of the raw materials was complete, and the mixture was cooled to room temperature. The reaction mixture was slowly poured into stirred ice water, stirred for 1 h, added DCM (3×50 mL) for extraction, the organic layer was added anhydrous MgSO 4 After drying, the solvent was evaporated to obtain a light yellow transparent liquid. The silica gel column was further purified to obtain a colorless transparent liquid, that is, compound 2 (yield 99%, purity 97%).

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Abstract

The invention discloses a preparation method of a compound shown in formula 2, comprising the following steps, in a solvent, compound 1 and PCl 5 Carry out chlorination reaction, get final product; Wherein, X is F, Cl, Br or I; Described solvent is selected from SOCl 2 , carbon tetrachloride, 1,2-dichloroethane, 1,1,1-trichloroethane, trichloroethylene and 1,1,2-trichloroethane; the preparation The method uses 5-halogenated uracil as the starting material, the process is simple, the yield is high and the environment is friendly, and it can be suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of halogenated uracil compounds. Background technique [0002] Palbociclib (Palbociclib), developed by Pfizer of the United States, is used as an initial regimen based on endocrine therapy, combined with letrozole for estrogen receptor-positive, human epidermal growth factor-treated patients who have not received systemic treatment. Receptor 2 negative (ER + / HER2 - ) in postmenopausal women with advanced breast cancer. [0003] The synthesis route of palbocoxib reported in patent WO2014128588A1 is as follows: [0004] [0005] This route uses 2,4-dichloro-5-bromopyrimidine as the starting material, and cyclopentylamine is ammonated to obtain 5-bromo-2-chloro-6-cyclopentylpyrimidine, which undergoes a Heck reaction with crotonic acid, and then 2-Chloro-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one is obtained by lactamation, and 6-bromo-2-chloro-8 is obtained by bromination -Cyclopentyl-5-m...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/30
CPCC07D239/30
Inventor 马庆童单晓燕陈旭东陈雨
Owner SHANGHAI INST OF PHARMA IND CO LTD
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