Sodium Hydroxide → 1-benzyl-N-(1H-indazol-5-yl)piperidine-4-carboxamide

HRID 1269732Notes

Reaction equation

HRID 1269732 reaction equation
S(Cl)(Cl)=O.[CH2:5]([N:12]1[CH2:17][CH2:16][CH:15]([C:18]([OH:20])=O)[CH2:14][CH2:13]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[NH2:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][N:26]=[CH:25]2.[OH-].[Na+]>C(Cl)Cl.CN(C)C1C=CN=CC=1.N1C=CC=CC=1.C(N(CC)CC)C>[CH2:5]([N:12]1[CH2:13][CH2:14][CH:15]([C:18]([NH:21][C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][CH:30]=2)[NH:27][N:26]=[CH:25]3)=[O:20])[CH2:16][CH2:17]1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 880121H-Indazol-5-amineHCID 47149831-Benzylpiperidine-4-carboxylic acid

Product 1

HCID 229334241-benzyl-N-(1H-indazol-5-yl)piperidine-4-carboxamideYield 30%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

Thionyl chloride (10.5 ml) was added to 1-benzyl-4-piperidinecarboxylic acid (4.85 g, 22.1 mmol), and the resulting mixture was refluxed for 2 hours. The reaction solution was distilled under reduced pressure to remove the solvent. To a solution of the resulting residue in methylene chloride (65 ml) were added 5-aminoindazole (4.41 g, 33.2 mmol), triethylamine (1.8 ml), pyridine (30 ml) and a catalytic amount of 4-dimethylaminopyridine at 0° C., and then stirred at room temperature for 3 hours. Then, the reaction solution was poured into a 1N-aqueous sodium hydroxide solution and extracted with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=20/1) to obtain 1-benzyl-N-(1H-indazol-5-yl)-4-piperidinecarboxamide (2.2 g, 30%).

Workup

  1. temperaturethe resulting mixture was refluxed for 2 hours
  2. distillationThe reaction solution was distilled under reduced pressure
  3. customto remove the solvent
  4. extractionextracted with chloroform
  5. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customthe resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=20/1)

Sources & evidence

ORD record
ord-acfc86fff2b7491e8914254f477d52fd
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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