Potassium Carbonate → methyl 4-((4,4,4-trifluoro-1-(2-methyl-4-(4,5,6,7-tetrahydro-2H-indazol-2-yl)phenyl)butyl)amino)benzoate

HRID 1520277Notes

Reaction equation

HRID 1520277 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:15][C:16]2[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=2)[CH2:9][CH2:10][C:11]([F:14])([F:13])[F:12])=[C:4]([CH3:26])[CH:3]=1.[NH:27]1[C:35]2[CH2:34][CH2:33][CH2:32][CH2:31][C:30]=2[CH:29]=[N:28]1.CN[C@@H]1CCCC[C@H]1NC.C(=O)([O-])[O-].[K+].[K+]>[Cu]I.O.C1(C)C=CC=CC=1>[F:12][C:11]([F:14])([F:13])[CH2:10][CH2:9][CH:8]([NH:15][C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=1)[C:5]1[CH:6]=[CH:7][C:2]([N:28]2[CH:29]=[C:30]3[C:35]([CH2:34][CH2:33][CH2:32][CH2:31]3)=[N:27]2)=[CH:3][C:4]=1[CH3:26]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 753174,5,6,7-tetrahydro-1H-indazoleHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 117840148Methyl 4-((1-(4-bromo-2-methylphenyl)-4,4,4-trifluorobutyl)amino)benzoate

Product 1

HCID 117840555methyl 4-((4,4,4-trifluoro-1-(2-methyl-4-(4,5,6,7-tetrahydro-2H-indazol-2-yl)phenyl)butyl)amino)benzoateYield 74.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Under a nitrogen atmosphere, a mixture of methyl 4-((1-(4-bromo-2-methylphenyl)-4,4,4-trifluorobutyl)amino)benzoate (racemate) (300 mg), 4,5,6,7-tetrahydroindazole (128 mg), copper(I) iodide (159 mg), trans-N,N′-dimethylcyclohexane-1,2-diamine (0.264 mL), potassium carbonate (289 mg) and toluene (1.4 mL) was stirred at 110° C. overnight. To the reaction mixture was added water at room temperature, and the insoluble material was filtered off through celite. The filtrate was extracted with ethyl acetate, and the extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (243.9 mg).

Workup

  1. filtrationthe insoluble material was filtered off through celite
  2. extractionThe filtrate was extracted with ethyl acetate
  3. washthe extract was washed with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a3825a3cef2249a4973d12ecf947a4cd
Source dataset
uspto-grants-2015_07
Patent number
US09073864B2

Reaction notes

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