Potassium Carbonate → N,N-dimethyl-4-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]benzamide

HRID 230649Notes

Reaction equation

HRID 230649 reaction equation
I[C:2]1[CH:12]=[CH:11][C:5]([C:6]([N:8]([CH3:10])[CH3:9])=[O:7])=[CH:4][CH:3]=1.[F:13][C:14]([F:25])([F:24])[C:15]1[C:23]2[CH2:22][CH2:21][CH2:20][CH2:19][C:18]=2[NH:17][N:16]=1.N[C@@H]1CCCC[C@H]1N.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.[Cu]I>[CH3:9][N:8]([CH3:10])[C:6](=[O:7])[C:5]1[CH:11]=[CH:12][C:2]([N:17]2[C:18]3[CH2:19][CH2:20][CH2:21][CH2:22][C:23]=3[C:15]([C:14]([F:13])([F:25])[F:24])=[N:16]2)=[CH:3][CH:4]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-3×HCID 8799334-iodo-N,N-dimethylbenzamideHCID 28028633-(Trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole

Product 1

HCID 945544N,N-dimethyl-4-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]benzamideYield 43.6%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
180 °C

Procedure

A mixture of 4-iodo-N,N-dimethylbenzamide (100 mg, 0.36 mmol), 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (83 mg, 0.44 mmol), copper (I) iodide (1 mol %, 0.7 mg, 0.0036 mmol), trans-1,2-diaminocyclohexane (10 mol %, 4 mg, 0.036 mmol) and potassium carbonate (105 mg, 0.76 mmol) in 1,4-dioxane (0.5 ml) was stirred at 180° C. in a microwave reactor for 15 minutes, then fresh copper (I) iodide (1 mol %, 0.7 mg, 0.0036 mmol) and trans-1,2-diaminocyclohexane (10 mol %, 4 mg, 0.036 mmol) were added and the reaction stirred at 180° C. in a microwave reactor for 20 minutes. Then fresh copper (I) iodide (1 mol %, 0.7 mg, 0.0036 mmol) and trans-1,2-diaminocyclohexane (10 mol %, 4 mg, 0.036 mmol) were added and the reaction stirred at 180° C. in a microwave reactor for 30 minutes. The reaction mix was cooled and added to a 5 g pre-packed silica column which was then eluted from ethyl acetate, the product was further purified by mass directed auto-prep to give a crop of the title compound as a brown oil (53 mg, 43%).

Workup

  1. stirringthe reaction stirred at 180° C. in a microwave reactor for 20 minutes
  2. stirringthe reaction stirred at 180° C. in a microwave reactor for 30 minutes
  3. additionThe reaction mix
  4. temperaturewas cooled
  5. additionadded to a 5 g pre-packed silica column which
  6. washwas then eluted from ethyl acetate
  7. customthe product was further purified by mass

Sources & evidence

ORD record
ord-9f350a00202c4d61998c88976c798e76
Source dataset
uspto-grants-2009_07
Patent number
US07566735B2

Reaction notes

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