Potassium Carbonate → phenylmethyl 3-(4-amino-6-methyl-1H-indazol-1-yl)benzoate

HRID 418786Notes

Reaction equation

HRID 418786 reaction equation
Cl.[CH3:2][C:3]1[CH:4]=[C:5]([NH2:12])[C:6]2[CH:7]=[N:8][NH:9][C:10]=2[CH:11]=1.I[C:14]1[CH:15]=[C:16]([CH:27]=[CH:28][CH:29]=1)[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18].C(=O)([O-])[O-].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC>CN(C=O)C.[Cu]I.C(OCC)(=O)C.O>[NH2:12][C:5]1[CH:4]=[C:3]([CH3:2])[CH:11]=[C:10]2[C:6]=1[CH:7]=[N:8][N:9]2[C:14]1[CH:15]=[C:16]([CH:27]=[CH:28][CH:29]=1)[C:17]([O:19][CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:18]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 22254461Benzyl 3-iodobenzoateHCID 66648350HCID 66648350, compound

Product 1

HCID 59010011phenylmethyl 3-(4-amino-6-methyl-1H-indazol-1-yl)benzoateYield 32.3%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-Methyl-1H-indazol-4-amine hydrochloride (0.5 g, 2.7 mmol), phenylmethyl 3-iodobenzoate (0.9 g, 2.6 mmol), copper (I) iodide (14 mg, 0.07 mmol), potassium carbonate (1.2 g, 8.68 mmol) and trans-N,N′-dimethyl-1,2-cyclohexanediamine (20 mg, 0.14 mmol) were heated together in DMF (5 mL) at reflux overnight. The mixture was cooled, poured into a mixture of water and ethyl acetate and filtered through celite. The organic phase was separated, combined with a second ethyl acetate extract, washed successively with water and brine and then dried over anhydrous sodium sulphate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (75 g) eluting with 1 to 5% gradient of ethyl acetate in dichloromethane to give the title compound (0.3 g).

Workup

  1. temperatureat reflux overnight
  2. temperatureThe mixture was cooled
  3. filtrationfiltered through celite
  4. customThe organic phase was separated
  5. extractionextract
  6. washwashed successively with water and brine
  7. dry with materialdried over anhydrous sodium sulphate
  8. customevaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (75 g)
  10. washeluting with 1 to 5% gradient of ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-b40f51b893df41e5b053b71a1ed042cd
Source dataset
uspto-grants-2012_01
Patent number
US08093281B2

Reaction notes

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