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

HRID 1269813Notes

Reaction equation

HRID 1269813 reaction equation
N1C2C(=CC(O)=CC=2)C=N1.[NH:11]1[C:19]2[C:14](=[CH:15][C:16]([O:20][C@H:21]3[CH2:26][CH2:25][CH2:24][C@H:23]([N:27]4C(=O)C5C(=CC=CC=5)C4=O)[CH2:22]3)=[CH:17][CH:18]=2)[CH:13]=[N:12]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC1C=CC=CC=1)=O)=NC(OCC1C=CC=CC=1)=O.ClCCl.CN.C(O)C>O1CCCC1>[NH:11]1[C:19]2[C:14](=[CH:15][C:16]([O:20][C@@H:21]3[CH2:26][CH2:25][CH2:24][C@H:23]([NH2:27])[CH2:22]3)=[CH:17][CH:18]=2)[CH:13]=[N:12]1

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 1014381H-Indazol-5-olHCID 22028356Methylamine ethanolHCID 69430700trans-2-[3-(1H-indazol-5-yloxy)cyclohexyl]-1H-isoindole-1,3(2H)-dioneHCID 86593608Dibenzyl azodicarboxylate dichloromethane

Product 1

HCID 69430632cis-3-(1H-indazol-5-yloxy)cyclohexanamineYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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%).

Workup

  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))

Sources & evidence

ORD record
ord-cbcb1b377c194e35bcb3a864029173cd
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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