Triethylamine → N-(1H-indazol-5-yl)-1-(methylsulfonyl)-4-piperidinecarboxamide

HRID 1269733Notes

Reaction equation

HRID 1269733 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][S:8]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]([OH:19])=O)[CH2:13][CH2:12]1)(=[O:10])=[O:9].[NH2:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][N:25]=[CH:24]2.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>C(Cl)Cl.CN(C)C=O>[NH:26]1[C:27]2[C:23](=[CH:22][C:21]([NH:20][C:17]([CH:14]3[CH2:13][CH2:12][N:11]([S:8]([CH3:7])(=[O:9])=[O:10])[CH2:16][CH2:15]3)=[O:19])=[CH:29][CH:28]=2)[CH:24]=[N:25]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 880121H-Indazol-5-amineHCID 516892Sodium BicarbonateHCID 7740121-Methanesulfonylpiperidine-4-carboxylic acid

Product 1

HCID 22933571N-(1H-indazol-5-yl)-1-(methylsulfonyl)-4-piperidinecarboxamideYield 86.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent4×

Procedure

A catalytic amount of N,N-dimethylformamide and a solution of oxalyl dichloride (0.367 g, 2.89 mmol) in methylene chloride (3 ml) were added to a solution of 1-(methylsulfonyl)-4-piperidinecarboxylic acid (500 mg, 2.41 mmol) in methylene chloride (7 ml), and the resulting mixture was stirred at room temperature for three and a half hours. The reaction solution was distilled under reduced pressure to remove the solvent, and a solution of the resulting residue in methylene chloride (5 ml) was added to a solution of 5-aminoindazole (322 mg, 2.42 mmol) and triethylamine (0.67 ml, 4.8 mmol) in methylene chloride (10 ml) at 0° C. and stirred overnight at room temperature. Then, the reaction solution was poured into a saturated aqueous sodium hydrogencarbonate solution and the organic solvent was distilled off under reduced pressure. The solid precipitated was collected by filtration and suspended in methanol, and the resulting suspension was stirred at 50° C., followed by filtration. The solid collected by this filtration was dried under reduced pressure to obtain N-(1H-indazol-5-yl)-1-(methylsulfonyl)-4-piperidinecarboxamide (670 mg, 86%).

Workup

  1. distillationThe reaction solution was distilled under reduced pressure
  2. customto remove the solvent
  3. stirringstirred overnight at room temperature
  4. distillationthe organic solvent was distilled off under reduced pressure
  5. customThe solid precipitated
  6. filtrationwas collected by filtration
  7. stirringthe resulting suspension was stirred at 50° C.
  8. filtrationfollowed by filtration
  9. filtrationThe solid collected by this filtration
  10. customwas dried under reduced pressure

Sources & evidence

ORD record
ord-b6a87ceb139b40048148c8a4670c9356
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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