反应详情

To 2-methyl-1-n-propylbenzimidazole-5-carboxylic acid (see Working Example 82-3) (1.0 g, 3.93 mmol) was added thionyl chloride (8 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 2-aminophenol (456 mg, 2.96 mmol), triethylamine (899 mg, 8.88 mmol) and tetrahydrofuran (10 mL), and this was stirred at room temperature for 14 hours. After the reaction was complete, this was concentrated, and to a dioxane (10 mL) solution of the residue obtained was added methanesulfonic acid (1.42 g, 14.8 mmol), and this was heated to reflux for 18 hours. After the reaction solution was cooled, water and saturated aqueous sodium hydrogen carbonate were added, the precipitated crystals were filtered, washed with water and dried. To the residue obtained was added iron powder (400 mg, 7.12 mmol), 10% aqueous acetic acid (20 mL), and ethanol (20 mL), and this was heated to reflux for 2 hours. After the reaction solution was cooled, a 1N aqueous sodium hydroxide solution and chloroform were added, this was filtered through Celite, and the filtrate obtained was extracted. 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, and the oil obtained was dissolved in tetrahydrofuran (3 mL), and to this was added a 1M solution of hydrogen chloride in diethyl ether (1 mL). The precipitated crystals were filtered, and after washing with tetrahydrofuran, they were dried to yield the title compound (168 mg, 25% yield) as light green 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 (10 mL) solution of the residue obtained
7. temperaturethis was heated
8. temperatureto reflux for 18 hours
9. temperatureAfter the reaction solution was cooled
10. filtrationthe precipitated crystals were filtered
11. washwashed with water
12. customdried
13. customTo the residue obtained
14. temperaturethis was heated
15. temperatureto reflux for 2 hours
16. temperatureAfter the reaction solution was cooled
17. filtrationthis was filtered through Celite
18. customthe filtrate obtained
19. extractionwas extracted
20. customAfter the organic layer obtained
21. dry with materialwas dried over anhydrous sodium sulfate, it
22. filtrationwas filtered
23. concentrationconcentrated
24. customThe residue obtained
25. customwas purified by silica gel column chromatography
26. customthe oil obtained
27. filtrationThe precipitated crystals were filtered
28. washafter washing with tetrahydrofuran, they
29. customwere dried