Water → (S)-5-Oxopyrrolidine-3-carboxylic acid{1-(4-fluorophenyl)-5-[3-fluoro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1H-pyrazol-3-yl}amide

HRID 83548Notes

Reaction equation

HRID 83548 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[C:17]([CH2:19][O:20][C@H:21]([CH3:26])[C:22]([F:25])([F:24])[F:23])[CH:16]=[C:15]([F:27])[CH:14]=3)=[CH:11][C:10]([NH2:28])=[N:9]2)=[CH:4][CH:3]=1.[O:29]=[C:30]1[NH:34][CH2:33][C@@H:32]([C:35](O)=[O:36])[CH2:31]1.CCN=C=NCCCN(C)C.Cl.O>CN(C)C=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[C:17]([CH2:19][O:20][C@H:21]([CH3:26])[C:22]([F:24])([F:25])[F:23])[CH:16]=[C:15]([F:27])[CH:14]=3)=[CH:11][C:10]([NH:28][C:35]([C@H:32]3[CH2:31][C:30](=[O:29])[NH:34][CH2:33]3)=[O:36])=[N:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 25100087(S)-5-oxopyrrolidine-3-carboxylic acidHCID 712878641-(4-Fluorophenyl)-5-[3-fluoro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1H-pyrazol-3-ylamine

Product 1

HCID 71287724(S)-5-Oxopyrrolidine-3-carboxylic acid{1-(4-fluorophenyl)-5-[3-fluoro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1H-pyrazol-3-yl}amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-fluorophenyl)-5-[3-fluoro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1H-pyrazol-3-ylamine prepared in the previous step (about 0.125 mmol) in dimethylformamide (0.5 ml) were sequentially added (S)-5-oxopyrrolidine-3-carboxylic acid (18 mg) prepared according to the same procedures as Preparation 14 and WSC.HCl (29 mg) at room temperature, and the mixture was stirred for 3 hours. To this reaction mixture was added water, and the mixture was extracted with ethyl acetate. This organic layer was concentrated under reduced pressure, the resulting residue was purified by silica gel thin-layer chromatography (eluent: chloroform/methanol=10/1). To the resulting solid were added water and a small amount of methanol, and the mixture was stirred. A solid was collected from this suspension by filtration, and was dried under reduced pressure to give the titled compound (31 mg).

Workup

  1. customprepared
  2. extractionthe mixture was extracted with ethyl acetate
  3. concentrationThis organic layer was concentrated under reduced pressure
  4. customthe resulting residue was purified by silica gel thin-layer chromatography (eluent: chloroform/methanol=10/1)
  5. additionTo the resulting solid were added water
  6. stirringa small amount of methanol, and the mixture was stirred
  7. filtrationA solid was collected from this suspension by filtration
  8. customwas dried under reduced pressure

Sources & evidence

ORD record
ord-6c4b468008a5416a85b2e37e2dcd652c
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Reaction notes

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