反应详情

To a mixture of 0.067 g (0.15 mmole) of 4-(3-chloro-phenyl)-2-[6-(3-hydroxy-propoxy)-5-methoxy-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide (I.42a), 0.036 g (0.36 mmole) of triethylamine and 2 mL of dimethylformamide at 0 degrees was added, 0.020 g (0.18 mmole) of methanesulfonyl chloride. The mixture was stirred for 1 hour and then 1 mL of saturated ammonium chloride solution was added dropwise. The mixture was poured into 25 mL of water and extracted three times with 20 mL of ethyl acetate. The combined organic extracts were washed three times with 25 mL of water, once with 25 mL of saturated sodium bicarbonate solution, once with 25 mL of brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was heated at 80 degrees for 1 hour with 2 mL of dimethylformamide and 0.080 mL of N-methylpiperazine. The mixture was cooled, poured into 25 mL of water extracted three times with 20 mL of ethyl acetate. The combined organic extracts were washed three times with 25 mL of water, once with 25 mL of saturated sodium bicarbonate solution, once with 25 mL of brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with methanol-dichloromethane (25:75) to give 0.026 g of 4-(3-chloro-phenyl)-2-{5-methoxy-6-[3-(4-methyl-piperazin-1-yl)-propoxy]-benzoimidazol-1-yl}thiazole-5-carboxylic acid amide (I.42) as a pink solid. MH+/Z=541

1. additionwas added
2. extractionextracted three times with 20 mL of ethyl acetate
3. washThe combined organic extracts were washed three times with 25 mL of water
4. dry with materialonce with 25 mL of saturated sodium bicarbonate solution, once with 25 mL of brine, dried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. temperatureThe residue was heated at 80 degrees for 1 hour with 2 mL of dimethylformamide and 0.080 mL of N-methylpiperazine
8. temperatureThe mixture was cooled
9. additionpoured into 25 mL of water
10. extractionextracted three times with 20 mL of ethyl acetate
11. washThe combined organic extracts were washed three times with 25 mL of water
12. dry with materialonce with 25 mL of saturated sodium bicarbonate solution, once with 25 mL of brine, dried over anhydrous magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customThe residue was purified by silica gel chromatography
16. washeluting with methanol-dichloromethane (25:75)