Potassium Carbonate → N-(1-{4-[3-(3,5-Dimethyl-isoxazol-4-yl)-ureido]-2-fluoro-phenyl}-piperidin-4-yl)-2-ethyl-N-phenyl-butyramide

HRID 1927600Notes

Reaction equation

HRID 1927600 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:15](=[O:21])[CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[CH2:10][CH2:9]2)=[C:4]([F:28])[CH:3]=1.C(C(CC)[C:32]([N:34]([C:41]1[CH:46]=[CH:45]C=[CH:43][CH:42]=1)C1CCNCC1)=[O:33])C.C([O-])([O-])=O.[K+].[K+].FC1C=CC([N+:62]([O-])=[O:63])=CC=1F>CN(C=O)C.O>[CH3:45][C:46]1[C:41]([NH:34][C:32](=[O:33])[NH:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH2:13][CH2:12][CH:11]([N:14]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:15](=[O:21])[CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[CH2:10][CH2:9]3)=[C:4]([F:28])[CH:3]=2)=[C:42]([CH3:43])[O:63][N:62]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 693036472-ethyl-N-phenyl-N-piperidin-4-yl-butyramideHCID 69305096N-[1-(4-amino-2-fluoro-phenyl)-piperidin-4-yl]-2-ethyl-N-phenyl-butyramide

Product 1

HCID 16667231N-(1-{4-[3-(3,5-Dimethyl-isoxazol-4-yl)-ureido]-2-fluoro-phenyl}-piperidin-4-yl)-2-ethyl-N-phenyl-butyramide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

N-[1-(4-amino-2-fluoro-phenyl)-piperidin-4-yl]-2-ethyl-N-phenyl-butyramide. To a mixture of 2-ethyl-N-phenyl-N-piperidin-4-yl-butyramide (10 mmol) and K2CO3 (40 mmol) in DMF (30 mL) was added 1,2-difluoro-4-nitro-benzene (1.6 g, 10 mmol). The reaction mixture was stirred at 50° C. for 3 h, then was diluted with H2O (500 mL). The solution was decanted, leaving a semi-solid, which was collected and re-dissolved into 1:1 EtOH/EtOAc (100 mL). The mixture was treated with SnCl2.2H2O (10 g) and was heated at 100° C. for 16 h. The mixture was cooled to rt, diluted with ice water (100 mL), basified to pH=9 with NaHCO3, and extracted with EtOAc (3×200 mL). The organic layers were combined, dried (Na2SO4), and concentrated to give the crude title compound.

Workup

  1. customThe solution was decanted
  2. customleaving a semi-solid, which
  3. customwas collected
  4. dissolutionre-dissolved into 1:1 EtOH/EtOAc (100 mL)
  5. additionThe mixture was treated with SnCl2.2H2O (10 g)
  6. temperaturewas heated at 100° C. for 16 h
  7. temperatureThe mixture was cooled to rt
  8. additiondiluted with ice water (100 mL)
  9. extractionextracted with EtOAc (3×200 mL)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-77606713bf5a461b827f2d1fdbd4d815
Source dataset
uspto-grants-2012_05
Patent number
US08183239B2

Reaction notes

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