Triphenylphosphine → 5-(azepin-4-yloxy)-4-chloro-1H-indazole

Under a nitrogen atmosphere, triphenylphosphine (280 mg, 1.07 mmol), the tert-butyl 4-hydroxyazepane-1-carboxylate (192 mg, 0.890 mmol) obtained in Example 322, (c) and diisopropyl azodicarboxylate (193 μl, 0.979 mmol) were added at 0° C. to a solution of the 4-chloro-1H-indazol-5-ol (150 mg, 0.890 mmol) obtained in Example 468 in tetrahydrofuran (6 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 (20 ml) and washed with a 1M-aqueous sodium hydroxide solution (10 ml). After the aqueous layer was re-extracted with chloroform (10 ml), 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 (3 ml) at room temperature and 4N-hydrochloric acid-dioxane (3 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) and 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-(azepin-4-yloxy)-4-chloro-1H-indazole (128.1 mg, 54%).

1. customthe mixture thus obtained
2. concentrationThe reaction solution was concentrated under reduced pressure
3. additionthe resulting residue was diluted with chloroform (20 ml)
4. washwashed with a 1M-aqueous sodium hydroxide solution (10 ml)
5. extractionAfter the aqueous layer was re-extracted with chloroform (10 ml)
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))

ORD 기록

ord-fb36641a0f5b481ca5665deef902c84e

출처 데이터셋

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07199147B2