反应详情

To a solution of 4-[2-[(2,4-dichlorophenyl)amino]-7-(diethylamino)-1H-benzimidazol-1-yl]butane-1,3-diol (Reference Example 84; 175 mg, 0.400 mmol) in pyridine (4 mL) was added methanesulfonyl chloride (0.0929 mL, 1.20 mmol) at 0° C. After the resultant mixture was stirred at 0° C. for 3 hr, the mixture was diluted with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting mesylate was diluted with N,N-dimethylformamide (4 mL) and to the solution was added potassium carbonate (110 mg, 0.797 mmol) at room temperature. After the resultant mixture was stirred at 80° C. for 1 hr, the mixture was diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 40% ethyl acetate/n-hexane mixture to give the title compound as a solid (108 mg, 0.258 mmol, 65%). Analytically pure material was obtained by recrystallization from ethyl acetate/n-hexane.

1. extractionextracted with ethyl acetate
2. washThe combined organic layer was washed with brine
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. additionThe resulting mesylate was diluted with N,N-dimethylformamide (4 mL) and to the solution
7. washwashed with water and brine
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe residue was purified by flash column chromatography on silica gel eluting with a 40% ethyl acetate/n-hexane mixture