1-Phenylcyclohexylamine → N-(1-phenylcyclohexyl)-1H-indazole-5-carboxamide

HRID 1269767Notes

Reaction equation

HRID 1269767 reaction equation
C(Cl)(=O)C(Cl)=O.[NH:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]([OH:18])=O)=[CH:13][CH:14]=2)[CH:9]=[N:8]1.[C:19]1([C:25]2([NH2:31])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)(O)[O-].[Na+]>ClCCl.O1CCCC1.CN(C)C=O>[C:19]1([C:25]2([NH:31][C:16]([C:12]3[CH:11]=[C:10]4[C:15](=[CH:14][CH:13]=3)[NH:7][N:8]=[CH:9]4)=[O:18])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

8

Reactant 4

HCID 318621-PhenylcyclohexylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 42484541H-Indazole-5-carboxylic acid

Product 1

HCID 22933990N-(1-phenylcyclohexyl)-1H-indazole-5-carboxamideYield 78.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Oxalyl dichloride (38.7 μl, 0.444 mmol) and N,N-dimethylformamide (about 1 μl) were added to a solution of the 1H-indazole-5-carboxylic acid (40.0 mg, 0.247 mmol) obtained in Reference Example 1 in dichloromethane (2.5 ml), and the resulting mixture was stirred at room temperature for 0.5 hour and then was stirred with heating under reflux for 2 hours while maintaining the temperature. The reaction solution was concentrated to dryness and a solution of the resulting residue in tetrahydrofuran (1.5 ml) was added dropwise to a solution of 1-phenylcyclohexylamine (130 mg, 0.742 mmol) in tetrahydrofuran (2.0 ml). The resulting mixture was stirred for 18 hours while being maintained at room temperature. A 5% aqueous sodium bicarbonate solution was added to the reaction solution and stirred, followed by extraction with ethyl acetate. The organic phase was washed with a 5% aqueous sodium chloride solution and then dried over anhydrous sodium sulfate. The organic phase dried was concentrated under reduced pressure, and the resulting crude product was purified by a silica gel column chromatography (eluent: chloroform/methanol=50/1 to 30/1) to obtain N-(1-phenylcyclohexyl)-1H-indazole-5-carboxamide (62 mg, 78%).

Workup

  1. stirringwas stirred
  2. temperaturewith heating
  3. temperatureunder reflux for 2 hours
  4. temperaturewhile maintaining the temperature
  5. concentrationThe reaction solution was concentrated to dryness
  6. stirringThe resulting mixture was stirred for 18 hours
  7. temperaturewhile being maintained at room temperature
  8. stirringstirred
  9. extractionfollowed by extraction with ethyl acetate
  10. washThe organic phase was washed with a 5% aqueous sodium chloride solution
  11. dry with materialdried over anhydrous sodium sulfate
  12. customThe organic phase dried
  13. concentrationwas concentrated under reduced pressure
  14. customthe resulting crude product was purified by a silica gel column chromatography (eluent: chloroform/methanol=50/1 to 30/1)

Sources & evidence

ORD record
ord-f3247dbfb8e94387b75be4ef97de35e0
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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