1H-Indazole → 1-(3-Methoxyphenyl)-1H-indazole

HRID 1050637Notes

Reaction equation

HRID 1050637 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1.I[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=1.C([O-])([O-])=O.[K+].[K+].[C@@H]1(N)CCCC[C@H]1N>[Cu]I.C1(C)C=CC=CC=1>[CH3:18][O:17][C:13]1[CH:12]=[C:11]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[N:2]2)[CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 92211H-IndazoleHCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 69839Benzene, 1-iodo-3-methoxy-

Product 1

HCID 112530791-(3-Methoxyphenyl)-1H-indazoleYield 98.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

To a dry pressure tube equipped with a magnetic stir bar was added 1H-indazole (3.54 g, 30 mmol, 1.0 eq), 1-iodo-3-methoxybenzene (8.07 g, 36 mmol, 1.2 eq), CuI (0.29 g, 1.5 mmol, 0.05 eq), K2CO3 (13.37 g, 63 mmol, 2.1 eq) and trans-1,2-cyclohexanediamine (0.65 g, 6 mmol, 0.2 eq). Then the tube was taken into a glove box and solvent toluene (40 mL) was added. The mixture was bubbled with nitrogen for 5 minutes and then the tube was sealed. The tube was taken out of the glove box and the mixture was stirred in an oil bath at 105-115° C. for 3 days. The mixture was cooled down to ambient temperature, diluted with ethyl acetate, and then filtered and washed with ethyl acetate. The filtrate was concentrated and the residue was purified through column chromatography on silica gel using hexane and ethyl acetate (20:1-10:1) as eluent to obtain the desired product as a colorless liquid 6.62 g in 98% yield. 1H NMR (DMSO-d6, 400 MHz): δ 3.85 (s, 3H), 6.98 (dd, J=8.0, 2.0 Hz, 1H), 7.25-7.30 (m, 2H), 7.35 (dd, J=8.0, 1.6 Hz, 1H), 7.49 (t, J=8.0 Hz, 2H), 7.86 (d, J=8.4 Hz, 1H), 7.89 (d, J=7.6 Hz, 1H), 8.37 (s, 1H). 13C NMR (DMSO-d6, 100 MHz): δ 55.40, 107.75, 110.59, 112.42, 114.12, 121.49, 121.70, 125.10, 127.55, 130.48, 135.69, 138.13, 140.83, 160.13.

Workup

  1. customTo a dry pressure tube equipped with a magnetic stir bar
  2. customThen the tube was taken into a glove box
  3. customThe mixture was bubbled with nitrogen for 5 minutes
  4. customthe tube was sealed
  5. temperatureThe mixture was cooled down to ambient temperature
  6. additiondiluted with ethyl acetate
  7. filtrationfiltered
  8. washwashed with ethyl acetate
  9. concentrationThe filtrate was concentrated
  10. customthe residue was purified through column chromatography on silica gel

Sources & evidence

ORD record
ord-75153550f477461fb50eebb0f8e3f573
Source dataset
uspto-grants-2016_07
Patent number
US09385329B2

Reaction notes

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