反应详情

This compound was prepared similarly to that of Example 525 by treating 3-(2-benzyl-7-trifluoromethyl-2H-indazole-3-yl)-phenol (23 mg, 1 eq) with 2-(4-bromomethyl-phenyl)-2-methyl-propionic acid methyl ester (17 mg, 1 eq) and potassium carbonate (26 mg, 3 eq) in acetone (2 mL). The latter reagent was obtained by heating p-tolyl-acetic acid in methanol and a catalytic amount of sulphuric acid. Subsequent methylation was accomplished by treating the obtained ester (50 mg, 1 eq) with sodium hydride (26 mg, 2.2 eq) and methyl iodide (41 μL, 2.2 eq) in THF (1 mL). Then α-bromination was accomplished by refluxing the ester (16 mg, 1 eq) with NBS (15 mg, 1 eq) and benzoyl peroxide (1 mg, 3%) in carbon tetrachloride (1.5 mL) overnight. The reaction mixture was cooled, water was added and product extracted with dichloromethane. The residue was purified by flash chromatography (ethyl acetate/n-heptane, 1:9, as an eluent). Then the resulting compound was then hydrolyzed with aq LiOH (1M, 40 eq)/THF, 1:1, and purified by preparative HPLC, affording the desired product in 26% yleld.

1. customThis compound was prepared similarly to that of Example 525
2. customThe latter reagent was obtained
3. temperatureThe reaction mixture was cooled
4. extractionproduct extracted with dichloromethane
5. customThe residue was purified by flash chromatography (ethyl acetate/n-heptane, 1:9