Picolinic acid → N-Cyclopropyl-N-[1-(pyridine-2-carbonyl)-piperidin-4-yl]-3-trifluoromethyl-benzenesulfonamide

HRID 1428959Notes

Reaction equation

HRID 1428959 reaction equation
[CH:1]1([N:4]([CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[S:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)(=[O:7])=[O:6])[CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[N:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[C:51](O)=[O:52]>CN(C=O)C>[CH:1]1([N:4]([CH:18]2[CH2:23][CH2:22][N:21]([C:51]([C:46]3[CH:47]=[CH:48][CH:49]=[CH:50][N:45]=3)=[O:52])[CH2:20][CH2:19]2)[S:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:15])[F:16])[CH:9]=2)(=[O:6])=[O:7])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 1018Picolinic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2773944N-Cyclopropyl-N-piperidin-4-yl-3-(trifluoromethyl)benzenesulfonamide

Product 1

HCID 24860755N-Cyclopropyl-N-[1-(pyridine-2-carbonyl)-piperidin-4-yl]-3-trifluoromethyl-benzenesulfonamideYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-Cyclopropyl-N-piperidin-4-yl-3-trifluoromethyl-benzenesulfonamide (0.174 g, 0.50 mmol), HOBt (0.068 g, 0.50 mmol), EDCI (0.115 g, 0.60 mmol) and picolinic acid (0.068 g, 0.55 mmol) were dissolved in 5 ml of dry DMF. The mixture allowed to stir at room temperature for 16 hours. The reaction mixture was concentrated to dryness under reduced pressure. Then residue was dissolved in EtOAc (30 ml) and the mixture was washed with saturated NaHCO3 (15 ml) and brine (15 ml). The organic layer was dried over MgSO4 and concentrated to dryness. The crude product was purified through a column of silica gel with a gradient of 0% to 10% MeOH in EtOAc to afford the title compound 7 (195 mg, 86%). The product was taken up in 2 ml of EtOAc. To the mixture, 2 ml of 4 N HCl in EtOAc was added. The solvent was removed and remaining material was the desired product 7 was obtained as a hydrochloride salt (pale yellow solid). LC: 100%. MS: m/z=453.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  2. dissolutionThen residue was dissolved in EtOAc (30 ml)
  3. washthe mixture was washed with saturated NaHCO3 (15 ml) and brine (15 ml)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated to dryness
  6. customThe crude product was purified through a column of silica gel with a gradient of 0% to 10% MeOH in EtOAc

Sources & evidence

ORD record
ord-bac9b75a96a34bc7883932cf004de850
Source dataset
uspto-grants-2015_01
Patent number
US08937181B2

Reaction notes

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