Triphenylphosphine → cis-3-(1H-indazol-5-yloxy)cyclohexanamine

To a solution of the 1H-indazol-5-ol (200 mg, 1.49 mmol) obtained in Reference Example 4 in tetrahydrofuran (15 ml) were added dropwise trans-2-[3-(1H-indazol-5-yloxy)cyclohexyl]-1H-isoindole-1,3(2H)-dione (366 mg, 1.49 mmol), triphenylphosphine (430 mg, 1.64 mmol) and a 40%-dibenzyl azodicarboxylate-dichloromethane solution (1.03 ml, 1.79 mmol) at 0° C. After 1 hour, the mixture thus obtained was warmed up to room temperature. After stirring overnight, the reaction solution was concentrated under reduced pressure, and the resulting residue was dissolved in chloroform (50 ml) and washed with a 1M-aqueous sodium hydroxide solution (20 ml). Extraction with chloroform (20 ml) was carried out again and 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) to obtain a mixture. To this mixture was added 30%-methylamine/ethanol (6 ml) under a nitrogen atmosphere at room temperature, after 15 minutes, then the resulting mixture was refluxed. After 3 hours, the reaction mixture was concentrated under reduced pressure at room temperature and the resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol→chloroform/methanol/(1% aqueous ammonia)) to obtain cis-3-(1H-indazol-5-yloxy)cyclohexanamine (98 mg, 29%).

1. customat 0° C
2. customthe mixture thus obtained
3. concentrationthe reaction solution was concentrated under reduced pressure
4. dissolutionthe resulting residue was dissolved in chloroform (50 ml)
5. washwashed with a 1M-aqueous sodium hydroxide solution (20 ml)
6. extractionExtraction with chloroform (20 ml)
7. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
8. customThe organic layer dried
9. concentrationwas concentrated under reduced pressure
10. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)
11. customto obtain a mixture
12. waitafter 15 minutes
13. temperaturethe resulting mixture was refluxed
14. waitAfter 3 hours
15. concentrationthe reaction mixture was concentrated under reduced pressure at room temperature
16. customthe resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol→chloroform/methanol/(1% aqueous ammonia))

ORD 기록

ord-cbcb1b377c194e35bcb3a864029173cd

출처 데이터셋

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07199147B2