反应详情

Under a nitrogen atmosphere, triphenylphosphine (146 mg, 0.559 mmol), tert-butyl 3-hydroxyazepane-1-carboxylate (100 mg, 0.466 mmol) and diisopropyl azodicarboxylate (101 μl, 0.512 mmol) were added at 0° C. to a solution of the 4-methyl-1H-indazol-5-ol (69 mg, 0.466 mmol) obtained in Example 402 in tetrahydrofuran (4 ml). After 30 minutes, the mixture thus obtained was warmed up to room temperature and stirred overnight. The reaction solution was concentrated under reduced pressure, and the resulting residue was diluted with chloroform and washed with a 1M-aqueous sodium hydroxide solution. After the aqueous layer was re-extracted with chloroform, the organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate). The oil thus obtained was dissolved in methanol (2 ml) at room temperature, and 4N-hydrochloric acid-dioxane (2 ml) was added thereto. After 1 hour, the mixture thus obtained was concentrated under reduced pressure and the resulting residue was dissolved in methanol (5 ml). The resulting solution was adjusted to pH 10 by dropwise addition of a 2M-aqueous sodium hydroxide solution. The solution adjusted was concentrated under reduced pressure and the resulting residue was re-dissolved in methanol (5 ml). Silica gel (1 g) was added thereto and the resulting mixture was concentrated under reduced pressure and then dried. The resulting solid was purified by a silica gel column chromatography (eluent: chloroform/methanol→chloroform/methanol (1%-aqueous ammonia)) to obtain 5-(azepan-3-yloxy)-4-methyl-1H-indazole (45.1 mg, 39%).

1. customthe mixture thus obtained
2. concentrationThe reaction solution was concentrated under reduced pressure
3. additionthe resulting residue was diluted with chloroform
4. washwashed with a 1M-aqueous sodium hydroxide solution
5. extractionAfter the aqueous layer was re-extracted with chloroform
6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
7. customThe organic layer dried
8. concentrationwas concentrated under reduced pressure
9. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)
10. customThe oil thus obtained
11. waitAfter 1 hour
12. customthe mixture thus obtained
13. concentrationwas concentrated under reduced pressure
14. dissolutionthe resulting residue was dissolved in methanol (5 ml)
15. additionThe resulting solution was adjusted to pH 10 by dropwise addition of a 2M-aqueous sodium hydroxide solution
16. concentrationThe solution adjusted was concentrated under reduced pressure
17. dissolutionthe resulting residue was re-dissolved in methanol (5 ml)
18. additionSilica gel (1 g) was added
19. concentrationthe resulting mixture was concentrated under reduced pressure
20. customdried
21. customThe resulting solid was purified by a silica gel column chromatography (eluent: chloroform/methanol→chloroform/methanol (1%-aqueous ammonia))