Triphenylphosphine → HCID 178511702, compound

HRID 1269786Notes

Reaction equation

HRID 1269786 reaction equation
[NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([OH:10])[C:4]=2[CH:3]=[N:2]1.[N+:11]([C:14]1[CH:39]=[CH:38][C:17](C(O[C@H]2CC[C@@H](N3C(=O)C4C(=CC=CC=4)C3=O)CC2)=O)=[CH:16][CH:15]=1)([O-])=O.O[C@@H]1CC[C@H](N2C(=O)C3C(=CC=CC=3)C2=O)CC1.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>O1CCCC1>[NH:1]1[C:9]2[C:4](=[C:5]([O:10][C@H:17]3[CH2:38][CH2:39][C@H:14]([NH2:11])[CH2:15][CH2:16]3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 86593608Dibenzyl azodicarboxylate dichloromethaneHCID 1357424501H-indazol-4-olHCID 178515016HCID 178515016, compoundHCID 178525746HCID 178525746, compound

Product 1

HCID 178511702HCID 178511702, compoundYield 5.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the 1H-indazol-4-ol (131 mg, 0.977 mmol) obtained in Example 320, (b) in tetrahydrofuran (10 ml) were added dropwise cis-2-(4-hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione (215 mg, 0.879 mmol), triphenylphosphine (283 mg, 1.07 mmol) and 40%-dibenzyl azodicarboxylate-dichloromethane solution (0.672 ml, 1.17 mmol) at 0° C. The resulting mixture was warmed up to room temperature 30 minutes after the addition. 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 the resulting mixture was added 30%-methylamine/ethanol (2 ml) at room temperature, and the resulting mixture was refluxed for 15 minutes. After 4 hours, the reaction solution was concentrated under reduced pressure at room temperature and the resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=10/1→chloroform/methanol/(1%-aqueous ammonia)=10/1) to obtain trans-4-(1H-indazol-4-yloxy)-cyclohexanamine (11 mg, 5.6%).

Workup

  1. additionafter the addition
  2. concentrationthe reaction solution was concentrated under reduced pressure
  3. dissolutionthe resulting residue was dissolved in chloroform (50 ml)
  4. washwashed with a 1M-aqueous sodium hydroxide solution (20 ml)
  5. extractionExtraction with chloroform (20 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. additionTo the resulting mixture was added 30%-methylamine/ethanol (2 ml) at room temperature
  11. temperaturethe resulting mixture was refluxed for 15 minutes
  12. waitAfter 4 hours
  13. concentrationthe reaction solution was concentrated under reduced pressure at room temperature
  14. customthe resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=10/1→chloroform/methanol/(1%-aqueous ammonia)=10/1)

Sources & evidence

ORD record
ord-960a9ee31af143f3ab4667765af20edf
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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