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

HRID 230683Notes

Reaction equation

HRID 230683 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[F:16][C:17]([F:28])([F:27])[C:18]1[C:26]2[CH2:25][CH2:24][CH2:23][CH2:22][C:21]=2[NH:20][N:19]=1.CN(C)CC(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.[Cu-]=O>[N:10]1([C:8]([C:5]2[CH:6]=[CH:7][C:2]([N:20]3[C:21]4[CH2:22][CH2:23][CH2:24][CH2:25][C:26]=4[C:18]([C:17]([F:16])([F:28])[F:27])=[N:19]3)=[CH:3][CH:4]=2)=[O:9])[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 7726344-[(4-Iodophenyl)carbonyl]morpholineHCID 28028633-(Trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole

Product 1

HCID 13166294-Morpholinyl{4-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]phenyl}methanoneYield 82%

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 4-[(4-iodophenyl)carbonyl]morpholine (1.90 g, 6.0 mmol), 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (1.14 g, 6.0 mmol), copper (I) oxide (10 mol %, 0.6 mmol, 86 mg), N,N-dimethylglycine (20 mol %, 1.2 mmol, 124 mg), and cesium carbonate (12.0 mmol, 3.91 g) in dimethylsulfoxide (16 ml) was stirred in an oilbath heated at 130° C. for 24 h under argon and then allowed to cool to room temperature. The reaction mixture was partitioned between dichloromethane (30 ml) and water (30 ml). The organic layer was separated and dried over sodium sulphate. The solvent was removed by rotary evaporation to give a dark brown residue that was added to a 20 g isolute pre-packed silica column and eluted from 0-50% ethyl acetate in petroleum ether to give the title compound as a brown gum (1.86 g, 82%).

Workup

  1. temperatureto cool to room temperature
  2. customThe reaction mixture was partitioned between dichloromethane (30 ml) and water (30 ml)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulphate
  5. customThe solvent was removed by rotary evaporation
  6. customto give a dark brown residue that
  7. additionwas added to a 20 g isolute pre-packed silica column
  8. washeluted from 0-50% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-6ad4561296a5482eb86433f37de142e2
Source dataset
uspto-grants-2009_07
Patent number
US07566735B2

Reaction notes

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