Cesium carbonate → 3-(3,5-Difluorophenoxy)-5-(1,3-dioxolan-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole

HRID 1038396Notes

Reaction equation

HRID 1038396 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:10]=[C:9]2I.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.CN(C)CC(O)=O.[F:38][C:39]1[CH:40]=[C:41]([OH:46])[CH:42]=[C:43]([F:45])[CH:44]=1>O1CCOCC1.[Cu]I>[F:38][C:39]1[CH:40]=[C:41]([CH:42]=[C:43]([F:45])[CH:44]=1)[O:46][C:9]1[C:8]2[C:12](=[CH:13][CH:14]=[C:6]([CH:2]3[O:3][CH2:4][CH2:5][O:1]3)[CH:7]=2)[N:11]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:10]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 759283,5-DifluorophenolHCID 584076045-(1,3-Dioxolan-2-yl)-3-iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole

Product 1

HCID 584076293-(3,5-Difluorophenoxy)-5-(1,3-dioxolan-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole

Reagents, catalysts & solvents 2

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

Conditions

Temperature
140 °C

Procedure

To a microwave-flask containing 300 mg (0.672 mmol) 5-(1,3-dioxolan-2-yl)-3-iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole (Example 6A), 438 mg (1.344 mmol) cesium carbonate and 19 mg (0.134 mmol) N,N-dimethylglycine hydrochloride in 1,4-dioxane (3 ml) were added 131 mg (1.008 mmol) 3,5-difluorophenol and 13 mg (0.067 mmol) copper(I) iodide. The flask was placed in an ultrasonic bath, and argon was bubbled through for a period of five minutes. The flask was then sealed and heated to 140° C. for 2 h using microwave irradiation. After this time, the same amounts of N,N-dimethylglycine hydrochloride and copper(I) iodide were added again, and heating was continued for further 2 h. This procedure was repeated one more time. Then, the reaction mixture was filtered, and the filtrate was purified by preparative RP-HPLC (acetonitrile/water+0.05% TFA gradient) to afford 43 mg (14% of th.) of the title compound.

Workup

  1. customThe flask was placed in an ultrasonic bath
  2. customargon was bubbled through for a period of five minutes
  3. customThe flask was then sealed
  4. custommicrowave irradiation
  5. additionAfter this time, the same amounts of N,N-dimethylglycine hydrochloride and copper(I) iodide were added again
  6. temperatureheating
  7. filtrationThen, the reaction mixture was filtered
  8. customthe filtrate was purified by preparative RP-HPLC (acetonitrile/water+0.05% TFA gradient)

Sources & evidence

ORD record
ord-1fa3070c698a4f0c9d127c709cf1c688
Source dataset
uspto-grants-2013_10
Patent number
US08551989B2

Reaction notes

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