反应详情

To 2-methyl-1-(tetrahydropyran-4-yl)benzimidazole-5-carboxylic acid HCl salt (see Working Example 4-3) (182 mg, 0.612 mmol) was added thionyl chloride (2 mL), and this was stirred at reflux for 3 hours. After the reaction was complete, concentration at reduced pressure gave a residue that was added to 4-trifluoromethyl-2-aminophenol (132 mg, 0.612 mmol), triethylamine (309 mg, 3.06 mmol) and tetrahydrofuran (5 mL), and this was stirred at room temperature for 14 hours. After the reaction was complete, this was concentrated, and to a dioxane (5 mL) solution of the residue obtained was added methanesulfonic acid (353 mg, 1.46 mmol), and this was heated to reflux for 18 hours. After the reaction solution was cooled, water and saturated aqueous sodium hydrogen carbonate solution were added, and this was extracted with chloroform. After the organic layer obtained was dried over anhydrous sodium sulfate, it was filtered and concentrated. The residue obtained was purified by silica gel column chromatography to yield the title compound (28.8 mg, 12% yield) as white crystals.

1. temperatureat reflux for 3 hours
2. concentrationconcentration at reduced pressure
3. customgave a residue that
4. stirringthis was stirred at room temperature for 14 hours
5. concentrationthis was concentrated
6. customto a dioxane (5 mL) solution of the residue obtained
7. temperaturethis was heated
8. temperatureto reflux for 18 hours
9. temperatureAfter the reaction solution was cooled
10. extractionthis was extracted with chloroform
11. customAfter the organic layer obtained
12. dry with materialwas dried over anhydrous sodium sulfate, it
13. filtrationwas filtered
14. concentrationconcentrated
15. customThe residue obtained
16. customwas purified by silica gel column chromatography