Diisopropylethylamine → (S)-2-[4-(6,7-Difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-yl)-piperazin-2-yl]-ethanol

참여 물질

반응 조건

반응 단계

Dissolve 6,7-difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride (1.51, 4.99 mmol), N,N-diisopropylethylamine (0.91 mL, 5.24 mmol) and (S)-2-piperazin-2-yl-ethanol (1.3 g, 9.99 mmol) in dimethylsulfoxide/toluene (1:2)(18 ml), stir under nitrogen and heat in an oil bath at 120° C. for 72 hours. Dilute the mixture with water (20 mL) and ethyl acetate (40 mL), separate layers and extract the aqueous with ethyl acetate. Combine all ethyl acetate extracts and wash with water and brine. Dry the organic phase (Na2SO4), filter and concentrate under reduced pressure. Purify by silica gel chromatography (eluent: 0-13% 2N ammonia in methanol/dichloromethane) to give 780 mg of impure product. Purify by silica gel chromatography (eluent: 85% dichloromethane/10% acetonitrile/0%2N ammonia in methanol to 80% dichloromethane/10% acetonitrile/10% 2N ammonia in methanol) to give the title compound (516 mg, 27%): Mass Spectrum (ESMS) 379 (M+1); 377 (M−1).

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