1-Hydroxybenzotriazole → 2-[2-(7-Methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]-N-Methylacetamide

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Reaction Steps

A mixture of [2-(7-methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (800 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (500 mg), 1-hydroxybenzotriazole (350 mg) and N,N-dimethylformamide (15 mL) was stirred at room temperature for 30 min. Then triethylamine (440 mg) and methylamine hydrochloride (230 mg) were added to the mixture. The whole was stirred at room temperature for 20-h. Water was added to the mixture and the resultant was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and brine, dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate:methanol=100:0 to 95:5, volume ratio) to give pale yellow crystals. The crystals were washed with ethyl acetate-hexane to give the title compound (540 mg, 67%) as pale yellow crystals. The crystals were recrystallized from acetone-hexane to give colorless prisms. MS 475 (MH+). mp 201-202° C.

Provenance & Evidence