Potassium Carbonate → 1-[4-(1H-imidazol-1-yl)phenyl]-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole

HRID 230690Notes

Reaction equation

HRID 230690 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[NH:5][N:4]=1.C(=O)([O-])[O-].[K+].[K+].N[C@@H]1CCCC[C@H]1N.Br[C:29]1[CH:34]=[CH:33][C:32]([N:35]2[CH:39]=[CH:38][N:37]=[CH:36]2)=[CH:31][CH:30]=1>O1CCOCC1.[Cu]I>[N:35]1([C:32]2[CH:33]=[CH:34][C:29]([N:5]3[C:6]4[CH2:7][CH2:8][CH2:9][CH2:10][C:11]=4[C:3]([C:2]([F:1])([F:12])[F:13])=[N:4]3)=[CH:30][CH:31]=2)[CH:39]=[CH:38][N:37]=[CH:36]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-3×HCID 27356041-(4-Bromophenyl)imidazoleHCID 28028633-(Trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole

Product 1

HCID 248261831-[4-(1H-imidazol-1-yl)phenyl]-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazoleYield 18%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst3×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
180 °C

Procedure

A mixture of 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (152 mg, 0.8 mmol), potassium carbonate (232 mg, 1.68 mmol) and copper (I) iodide (1 mg, 0.005 mmol) was treated with a solution of trans-1,2-diaminocyclohexane (9 mg, 0.08 mmol) in dioxane followed by a solution of 1-(4-bromophenyl)imidazole (161 mg, 0.72 mmol) in dioxane (4 ml total volume). This mixture was heated at 180° C. in a microwave reactor for 1 hour. Further copper (I) iodide (1 mg) and trans-1,2-diaminocyclohexane (9 mg) was added and the reaction heated at 180° C. in a microwave reactor for a further hour. Again further copper (I) iodide (1 mg) and trans-1,2-diaminocyclohexane (9 mg) was added and the reaction heated at 180° C. in a microwave reactor for a further hour. The reaction mixture was added to a 5 g sep-pack column and eluted with ethyl acetate. The solvent was removed by rotary evaporation and the crude product further purified by MDAP. Further purified using a 5 g SCX column, eluting from 1M ammonia in methanol which was then evaporated off using rotary evaporation to give the title compound (42 mg, 18%).

Workup

  1. temperaturethe reaction heated at 180° C. in a microwave reactor for a further hour
  2. temperaturethe reaction heated at 180° C. in a microwave reactor for a further hour
  3. additionThe reaction mixture was added to a 5 g sep-pack column
  4. washeluted with ethyl acetate
  5. customThe solvent was removed by rotary evaporation
  6. customthe crude product further purified by MDAP
  7. customFurther purified
  8. washeluting from 1M ammonia in methanol which
  9. customwas then evaporated off
  10. customevaporation

Sources & evidence

ORD record
ord-d439efabbcf54fc9aadf9559427a9765
Source dataset
uspto-grants-2009_07
Patent number
US07566735B2

Reaction notes

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