反应详情

The compound obtained in Referential Example 61 (1.40 g) was dissolved in N,N-dimethylformamide (15 mL), and to the solution were added 5-chloroindole-2-carboxylic acid (1.64 g), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.68 g), and 1-hydroxybenzotriazole monohydrate (473 mg), followed by stirring at room temperature for 23 hours. The solvent was distilled away under reduced pressure, and to the residue were added methylene chloride and saturated aqueous sodium hydrogencarbonate. The resultant precipitate was collected by filtration, and the precipitate was washed with ethyl acetate, methylene chloride, and methanol. Aside from this, the filtrate was partitioned, and the organic layer was separated, followed by drying over sodium sulfate anhydrate. The solvent was distilled away under reduced pressure, and the residue was purified by silica gel flash column chromatography (methylene chloride:methanol=19:1), to thereby give a pale-yellow solid. This pale-yellow solid was combined with the precipitate collected by the above-described filtration, and this mixture was dissolved in methylene chloride (10 mL). Trifluoroacetic acid (10 mL) was added thereto, and the thus-obtained mixture was stirred at room temperature for 3 hours. The solvent was distilled away under reduced pressure, and to the residue were added methylene chloride and 1N aqueous sodium hydroxide. The resultant precipitate was collected by filtration. The organic layer of the filtrate was separated, and was dried over sodium sulfate anhydrate. To the solution was added the precipitate collected by the above-described filtration, and a 4N HCl-dioxane solution (20 mL) was added thereto. The solvent was distilled away under reduced pressure, and after methylene chloride (10 mL) and a 4N HCl-dioxane solution (10 mL) were added to the residue, the solvent was distilled away again under reduced pressure. Ethyl acetate was added to the residue, and the resultant precipitate was collected by filtration, to thereby give the title compound (1.83 g).

1. distillationThe solvent was distilled away under reduced pressure
2. additionto the residue were added methylene chloride and saturated aqueous sodium hydrogencarbonate
3. filtrationThe resultant precipitate was collected by filtration
4. washthe precipitate was washed with ethyl acetate, methylene chloride, and methanol
5. customAside from this, the filtrate was partitioned
6. customthe organic layer was separated
7. dry with materialby drying over sodium sulfate anhydrate
8. distillationThe solvent was distilled away under reduced pressure
9. customthe residue was purified by silica gel flash column chromatography (methylene chloride:methanol=19:1)
10. customto thereby give a pale-yellow solid
11. filtrationcollected by the above-described filtration
12. dissolutionthis mixture was dissolved in methylene chloride (10 mL)
13. additionTrifluoroacetic acid (10 mL) was added
14. stirringthe thus-obtained mixture was stirred at room temperature for 3 hours
15. distillationThe solvent was distilled away under reduced pressure
16. additionto the residue were added methylene chloride and 1N aqueous sodium hydroxide
17. filtrationThe resultant precipitate was collected by filtration
18. customThe organic layer of the filtrate was separated
19. dry with materialwas dried over sodium sulfate anhydrate
20. additionTo the solution was added the precipitate
21. filtrationcollected by the above-described filtration
22. additiona 4N HCl-dioxane solution (20 mL) was added
23. distillationThe solvent was distilled away under reduced pressure
24. additionafter methylene chloride (10 mL) and a 4N HCl-dioxane solution (10 mL) were added to the residue
25. distillationthe solvent was distilled away again under reduced pressure
26. additionEthyl acetate was added to the residue
27. filtrationthe resultant precipitate was collected by filtration