1-Hydroxybenzotriazole → (3R,4R)-4-Methyl-5-oxopyrrolidine-3-carboxylic acid[1-(4-fluorophenyl)-5-(3-(trifluoromethoxy)phenyl)-1H-pyrazol-3-yl]amide

HRID 83495Notes

Reaction equation

HRID 83495 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:23])([F:22])[F:21])[CH:14]=3)=[CH:11][C:10]([NH2:24])=[N:9]2)=[CH:4][CH:3]=1.[CH3:25][C@H:26]1[C:30](=[O:31])[NH:29][CH2:28][C@@H:27]1[C:32](O)=[O:33].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C)C=O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:22])([F:21])[F:23])[CH:14]=3)=[CH:11][C:10]([NH:24][C:32]([C@@H:27]3[C@@H:26]([CH3:25])[C:30](=[O:31])[NH:29][CH2:28]3)=[O:33])=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 712877381-(4-Fluorophenyl)-5-(3-(trifluoromethoxy)phenyl)-1H-pyrazol-3-ylamineHCID 86680348(3R,4R)-4-Methyl-5-oxopyrrolidine-3-carboxylic Acid

Product 1

HCID 71287729(3R,4R)-4-Methyl-5-oxopyrrolidine-3-carboxylic acid[1-(4-fluorophenyl)-5-(3-(trifluoromethoxy)phenyl)-1H-pyrazol-3-yl]amideYield 64.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-fluorophenyl)-5-(3-(trifluoromethoxy)phenyl)-1H-pyrazol-3-ylamine (90 mg) in N,N-dimethylformamide (0.9 ml) were added (3R,4R)-4-methyl-5-oxopyrrolidine-3-carboxylic acid (50 mg) prepared in Preparation 1, HOBt.H2O (61 mg) and WSC.HCl (77 mg), and the mixture was stirred at room temperature for 2 hours. To this mixture were added water and a saturated aqueous solution of sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The separated organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel thin-layer chromatography (eluent: chloroform/methanol=10/1) to give the titled compound (80 mg).

Workup

  1. extractiona saturated aqueous solution of sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate
  2. washThe separated organic layer was washed with a saturated aqueous solution of sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel thin-layer chromatography (eluent: chloroform/methanol=10/1)

Sources & evidence

ORD record
ord-17aff64026cc419ea10a7efa14e40c3b
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Reaction notes

Loading…