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

HRID 230687Notes

Reaction equation

HRID 230687 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]([CH3:17])[C:10]([N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1.[F:18][C:19]([F:30])([F:29])[C:20]1[C:28]2[CH2:27][CH2:26][CH2:25][CH2:24][C:23]=2[NH:22][N:21]=1.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[CH3:17][N:9]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([N:22]2[C:23]3[CH2:24][CH2:25][CH2:26][CH2:27][C:28]=3[C:20]([C:19]([F:18])([F:30])[F:29])=[N:21]2)=[CH:3][CH:4]=1)[C:10]([N:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1)=[O:11]

Participants

7

Reactant 4

HCID 673N,N-Dimethylglycine2×HCID 11430Potassium CarbonateHCID 28028633-(Trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazoleHCID 57762825N-[(4-bromophenyl)methyl]-N-methyl-1-pyrrolidinecarboxamide

Product 1

HCID 57762823N-methyl-N-({4-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]phenyl}methyl)-1-pyrrolidinecarboxamideYield 4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
190 °C

Procedure

A mixture of N-[(4-bromophenyl)methyl]-N-methyl-1-pyrrolidinecarboxamide (250 mg, crude), 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (152 mg, 0.8 mmol), N,N-dimethylglycine (20 mol %, 16.5 mg, 0.16 mmol), copper (I) iodide (10 mol %, 15 mg, 0.08 mmol) and potassium carbonate (1.6 mmol, 221 mg) in dimethylsulfoxide (4 ml) was stirred at 190° C. in a microwave reactor for 30 minutes. The reaction mix was treated with fresh N,N-dimethylglycine and copper (I) iodide and heated at 190° C. in a microwave reactor for a further 30 minutes. The reaction mix was partitioned between dichloromethane (5 ml) and water (5 ml). The organic layer was added to a 5 g isolute silica sep-pak column and eluted with ethyl acetate. The solvent was removed under reduced pressure and the residue purified by mass directed auto-prep (MDAP) to give the title compound as a brown oil (12 mg, 4%).

Workup

  1. additionThe reaction mix
  2. temperatureheated at 190° C. in a microwave reactor for a further 30 minutes
  3. additionThe reaction mix
  4. customwas partitioned between dichloromethane (5 ml) and water (5 ml)
  5. additionThe organic layer was added to a 5 g isolute silica sep-pak column
  6. washeluted with ethyl acetate
  7. customThe solvent was removed under reduced pressure
  8. customthe residue purified by mass

Sources & evidence

ORD record
ord-633c61be661d428aaa55aab1094b9a6c
Source dataset
uspto-grants-2009_07
Patent number
US07566735B2

Reaction notes

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