N,N-Dimethylglycine → 1-methyl-5-{4-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]phenyl}-2-pyrrolidinone

HRID 230682Notes

Reaction equation

HRID 230682 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:12]([CH3:13])[C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[F:15][C:16]([F:27])([F:26])[C:17]1[C:25]2[CH2:24][CH2:23][CH2:22][CH2:21][C:20]=2[NH:19][N:18]=1.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[CH3:13][N:12]1[CH:8]([C:5]2[CH:6]=[CH:7][C:2]([N:19]3[C:20]4[CH2:21][CH2:22][CH2:23][CH2:24][C:25]=4[C:17]([C:16]([F:15])([F:27])[F:26])=[N:18]3)=[CH:3][CH:4]=2)[CH2:9][CH2:10][C:11]1=[O:14]

Participants

7

Reactant 4

HCID 673N,N-DimethylglycineHCID 11430Potassium CarbonateHCID 28028633-(Trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazoleHCID 577627945-(4-Bromophenyl)-1-methyl-2-pyrrolidinone

Product 1

HCID 248259091-methyl-5-{4-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]phenyl}-2-pyrrolidinoneYield 7%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
180 °C

Procedure

A mixture of 5-(4-bromophenyl)-1-methyl-2-pyrrolidinone (141 mg, 0.56 mmol), 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (111 mg, 0.58 mmol), copper (I) iodide (10 mol %, 11 mg, 0.06 mmol), N,N-dimethylglycine (20 mol %, 12 mg, 0.12 mmol) and potassium carbonate (162 mg, 1.17 mmol) in dimethylsulfoxide (3 ml) was stirred at 180° C. in a microwave reactor for a total of 2 h. The reaction mix was filtered through a 5 g pre-packed silica column washing through with dichloromethane (20 ml), the filtrate was washed with water (50 ml) and the organic layer dried over sodium sulphate. The solvent was removed by rotary evaporation and the sample purified by mass directed auto prep. The final product was partitioned between dichloromethane (3 ml) and water (3 ml). The organic layer was separated and solvent removed by rotary evaporation to give the title compound as a brown oil (14 mg, 7%)

Workup

  1. additionThe reaction mix
  2. filtrationwas filtered through a 5 g pre-packed silica column
  3. washwashing through with dichloromethane (20 ml)
  4. washthe filtrate was washed with water (50 ml)
  5. dry with materialthe organic layer dried over sodium sulphate
  6. customThe solvent was removed by rotary evaporation
  7. customthe sample purified by mass
  8. customThe final product was partitioned between dichloromethane (3 ml) and water (3 ml)
  9. customThe organic layer was separated
  10. customsolvent removed by rotary evaporation

Sources & evidence

ORD record
ord-efbdc9926752420788d19c0c91a3d1d7
Source dataset
uspto-grants-2009_07
Patent number
US07566735B2

Reaction notes

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