反应详情

(RS)-1-[2-(5,6-Difluoro-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone, E35 (300 mg, 0.64 mmol) was added slowly to an ice-cooled slurry of sodium hydride (51 mg, 1.3 mmol, 60% dispersion in mineral oil) in DMF (10 ml). After stirring for 0.5 h 1-bromo-2-methoxy-ethane (139 mg, 10 mmol), N,N-diisopropylethylamine (0.3 ml) and potassium iodide (5 mg) was added. The mixture was stirred at room temperature for 0.5 h then 100° C. for 16 h. The volatiles were removed in vacuo from the cooled reaction mixture. The residue was partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate (2×). The combined organics were dried (Na2SO4) and the solvent removed in vacuo. The residue was triturated with ethyl acetate to afford the title compound as a solid (306 mg, 65%).

1. additionwas added
2. wait100° C. for 16 h
3. customThe volatiles were removed in vacuo from the cooled reaction mixture
4. customThe residue was partitioned between ethyl acetate and water
5. extractionThe aqueous phase was extracted with ethyl acetate (2×)
6. dry with materialThe combined organics were dried (Na2SO4)
7. customthe solvent removed in vacuo
8. customThe residue was triturated with ethyl acetate