Application background and overview of 5-aldehyde-2-methoxyphenylboronic acid
5-Aldehyde-2-methoxyphenylboronic acid is a pharmaceutical intermediate that can be used to prepare a class of LSD1 inhibitors with a trans-diarylethene structure. The discovery of new, highly active LSD1 inhibitors is of great significance for studying the biological functions of LSD1 and developing new anti-tumor, anti-viral and other disease treatment drugs.
Applications of 5-aldehyde-2-methoxyphenylboronic acid
Preparation method of compound 1: 5-aldehyde-2-methoxyphenylboronic acid and substituted 2-bromopyridine or substituted 2-bromopyrimidine are reacted with reflux stirring in toluene in the presence of a basic compound and a palladium catalyst, Obtain compound 1. Wherein, the basic compound is selected from one of potassium carbonate, sodium carbonate, cesium carbonate and potassium phosphate, and the palladium catalyst is selected from tetrakis(triphenylphosphine) palladium, palladium acetate, bis(dibenzylidene) Acetone), one of palladium and palladium dichloride.
Preparation method of compound 2: Compound 1 and substituted benzyl phosphonate diethyl ester are stirred at room temperature in DMF in the presence of a strong basic compound. After the reaction is completed, the reaction system is poured into ice water and filtered with suction. , wash, collect the solid, and dry to obtain compound 2. Wherein, the strong basic compound is selected from one of potassium tert-butoxide, sodium methoxide, sodium hydride and sodium tert-butoxide.
Preparation method of compound 3: When R4 in compound 2 is nitro, in an organic solvent, in the presence of SnCl2, the reaction is stirred under reflux. After the reaction is completed, the reaction system is concentrated in vacuum, and ethyl acetate and saturated carbonic acid are added to the concentrate. The sodium hydrogen aqueous solution was stirred, and the organic phase was separated, washed, dried, and separated by column chromatography to obtain compound 3. Wherein, the organic solvent is selected from one of ethanol, ethyl acetate, and tetrahydrofuran.
Preparation method of compound 4: When R4 in compound 2 is a cyano group, react in anhydrous dichloromethane in the presence of boron tribromide at -35°C-room temperature overnight. After the reaction is completed, pour the reaction system Pour into saturated sodium bicarbonate water-soluble potassium trifluoroborate solution, filter with suction, collect the solid, and separate by column chromatography to obtain compound 4.
Preparation method of compound I: Compound 4 is reacted with hydroxylamine toluene boric acid in methanol in the presence of a strong basic compound under reflux and stirring. After the reaction is completed, the reaction system is concentrated in vacuum, and the concentrate is added to ethyl acetate and water for extraction. After washing, the organic phase was separated by column chromatography to obtain compound I. Wherein, the strong basic compound is selected from one of potassium carbonate, cesium carbonate, triethylamine, and N,N-diisopropylethylamine.
Or react compound 3 in anhydrous methylene chloride in the presence of boron tribromide at -35°C-room temperature. After the reaction is completed, pour the reaction system into a saturated sodium bicarbonate aqueous solution, filter with suction, and collect The solid was separated by column chromatography to obtain compound I.
References
[1] [Chinese invention, Chinese invention authorization] CN201710750071.7 A type of trans-diarylethene LSD1 inhibitor, its preparation method and application
