反应详情

2-(2-(2-Chloro-N-cyclopropyl-6-methylphenylsulfonamido)ethoxy)acetic acid (AC27) (100 mg, 0.288 mmol), O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uronium tetrafluoroborate (92 mg, 0.288 mmol) and 1-hydroxybenzotriazole hydrate (40 mg, 0.288 mmol) were dissolved in tetrahydrofuran (3.5 ml) and the mixture was stirred at room temperature for 30 min. A solution of 2-(azetidin-1-ylmethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine dihydrochloride (TP13) (97 mg, 0.346 mmol) and N-ethyl-diisopropylamine (146 μl, 0.864 mmol) in tetrahydrofuran (3.5 ml) was added and the mixture was stirred at room temperature overnight. The solvent was removed in vacuo, the residue was dissolved in ethyl acetate and saturated sodium hydrogen carbonate solution and the phases were separated. The aqueous phase was extracted with ethyl acetate (3×) and the combined organic layers were washed with saturated sodium chloride solution (1×), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica) with ethyl acetate/methanol 5/1. Yield: 100 mg (64%).

1. stirringthe mixture was stirred at room temperature overnight
2. customThe solvent was removed in vacuo
3. dissolutionthe residue was dissolved in ethyl acetate
4. customsaturated sodium hydrogen carbonate solution and the phases were separated
5. extractionThe aqueous phase was extracted with ethyl acetate (3×)
6. washthe combined organic layers were washed with saturated sodium chloride solution (1×)
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by column chromatography (silica) with ethyl acetate/methanol 5/1