Uses
1-(2,4-Dihydroxy-5-isopropylphenyl)ethanone acts as a reagent in the synthesis of 3,5-disubstituted-4-alkynylisoxozales as HSP90 inhibitors against various human cancer cell lines.
Synthesis
First, 4-isopropylbenzene-1,3-diol (I-4, 5.36 g, 35.25 mmol) was added to a unit equipped with two 250 mL flasks and a reflux condenser. Under nitrogen protection, 100 mL of 47% boron trifluoride ether solution was slowly injected for half an hour. Subsequently, 4.03 mL of glacial acetic acid was added and heated to reflux overnight in an oil bath. Upon completion of the reaction, the progress of the reaction was monitored by thin layer chromatography (TLC). After the reaction mixture was cooled to room temperature, 70 mL of 10% aqueous sodium acetate solution was added and stirred for 2 hours. The mixture was diluted to 250 mL with water and then extracted three times with ethyl acetate. The organic layers were combined and the solvent was removed by rotary evaporation. The organic phase was dried with anhydrous sodium sulfate and filtered to give a reddish brown solid. The solid was slurried in dichloromethane, which yielded a light yellow insoluble material upon addition. Filtration through a glass funnel and washing with dichloromethane resulted in 6.80 g of light yellow solid, the target compound I-5, in 99.4% yield.
References
[1] Patent: CN105439972, 2016, A. Location in patent: Paragraph 0094; 0095; 0107; 0108; 0109
[2] Journal of Medicinal Chemistry, 2008, vol. 51, # 2, p. 196 - 218
[3] Patent: CN103724269, 2016, B. Location in patent: Paragraph 0388; 0389; 0403; 0404; 0405; 0406
[4] Patent: US2009/76006, 2009, A1. Location in patent: Page/Page column 32; 41
[5] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 16, p. 3129 - 3134
