886497-81-0

352-67-0

68-12-2

886497-81-0

Example 49 3-Trifluoromethoxy-10-methyl-9H-imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine  was synthesized as follows: a) Preparation of 2-fluoro-5-(trifluoromethoxy)benzaldehyde: 1-fluoro-4-(trifluoromethoxy)benzene (21.0 g, 117 mmol) was dissolved in tetrahydrofuran (THF, 233 mL) under dry conditions, and cooled to 4°C. A hexane solution of n-butyllithium (n-BuLi) was slowly added and the reaction temperature was kept below 10°C. The reaction mixture was ether The reaction mixture was extracted with ethyl ether and the organic phases were combined, washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. After concentration under reduced pressure, it was purified by silica gel column chromatography (eluent: heptane/ethyl acetate=100:0 to 80:2) to obtain 2-fluoro-5-(trifluoromethoxy)benzaldehyde (11.0 g, yield 53%) as a light yellow oil. 1H-NMR (300 MHz, DMSO-d6): δ=7.60 (t, J=9.2 Hz, 1H), 7.75-7.85 (m, 2H), 10.20 (s, 1H).