N,N-Dimethylglycine → 1-{4-[1-methyl-2-oxo-2-(1-pyrrolidinyl)ethyl]phenyl}-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole

HRID 230667Notes

Reaction equation

HRID 230667 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:16])[C:9]([N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.[F:17][C:18]([F:29])([F:28])[C:19]1[C:27]2[CH2:26][CH2:25][CH2:24][CH2:23][C:22]=2[NH:21][N:20]=1.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[CH3:16][CH:8]([C:5]1[CH:6]=[CH:7][C:2]([N:21]2[C:22]3[CH2:23][CH2:24][CH2:25][CH2:26][C:27]=3[C:19]([C:18]([F:17])([F:29])[F:28])=[N:20]2)=[CH:3][CH:4]=1)[C:9](=[O:10])[N:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 673N,N-DimethylglycineHCID 11430Potassium CarbonateHCID 28028633-(Trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazoleHCID 577628121-[2-(4-Bromophenyl)propanoyl]pyrrolidine

Product 1

HCID 248271391-{4-[1-methyl-2-oxo-2-(1-pyrrolidinyl)ethyl]phenyl}-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazoleYield 4.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
190 °C

Procedure

A mixture of 1-[2-(4-bromophenyl)propanoyl]pyrrolidine (140 mg, 0.5 mmol), 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (95 mg, 0.5 mmol), copper (I) iodide (10 mol %, 10 mg, 0.05 mmol), N,N-dimethylglycine (20 mol %, 10 mg, 0.1 mmol) and potassium carbonate (138 mg, 1 mmol) in dimethylsulfoxide (2 ml) was stirred at 190° C. in a microwave reactor for a total of 1.5 h. The reaction mix was cooled and partitioned between ethyl acetate and water. The organic layer was dried over sodium sulphate and the solvent removed under reduced pressure. The resulting product was purified firstly by adding the material in dichloromethane to a 5 g pre-packed silica column and eluting with ethyl acetate, followed by mass directed auto-prep to give a crop of the title compound as a brown oil (8 mg, 4%).

Workup

  1. additionThe reaction mix
  2. temperaturewas cooled
  3. custompartitioned between ethyl acetate and water
  4. dry with materialThe organic layer was dried over sodium sulphate
  5. customthe solvent removed under reduced pressure
  6. customThe resulting product was purified firstly
  7. additionby adding the material in dichloromethane to a 5 g pre-packed silica column
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-96be296e506549e6be5495f1780ea603
Source dataset
uspto-grants-2009_07
Patent number
US07566735B2

Reaction notes

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