Potassium Carbonate → N-(2-Methoxymethylimidazo[1,2-a]pyrid-7-yl)-5-fluoro-1-[(3-fluorophenyl)-methyl]-1H-indole-2-carboxamide

HRID 1943998Notes

Reaction equation

HRID 1943998 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=1)[C:6]([C:19]([NH2:21])=[O:20])=[CH:5]2.Br[C:23]1[CH:28]=[CH:27][N:26]2[CH:29]=[C:30]([CH2:32][O:33][CH3:34])[N:31]=[C:25]2[CH:24]=1.C(=O)([O-])[O-].[K+].[K+].[C@@H]1(N)CCCC[C@H]1N>[Cu](I)I.O.O1CCOCC1>[CH3:34][O:33][CH2:32][C:30]1[N:31]=[C:25]2[CH:24]=[C:23]([NH:21][C:19]([C:6]3[N:7]([CH2:11][C:12]4[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=4)[C:8]4[C:4]([CH:5]=3)=[CH:3][C:2]([F:1])=[CH:10][CH:9]=4)=[O:20])[CH:28]=[CH:27][N:26]2[CH:29]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 581039787-Bromo-2-methoxymethylimidazo[1,2-a]pyridineHCID 668456965-Fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamide

Product 1

HCID 66863766N-(2-Methoxymethylimidazo[1,2-a]pyrid-7-yl)-5-fluoro-1-[(3-fluorophenyl)-methyl]-1H-indole-2-carboxamideYield 91.6%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

20 mg (0.09 mmol) of copper iodide, 40 mg (0.14 mmol) of 5-fluoro-1-[(3-fluorophenyl)-methyl]-1H-indole-2-carboxamide, prepared according to the protocol described in step 1.2, 27 mg (0.11 mmol) of 7-bromo-2-methoxymethylimidazo[1,2-a]pyridine, prepared according to the protocol described in step 8.3, 50 mg (0.36 mmol) of potassium carbonate and 3 mL of anhydrous dioxane are placed in a 10 mL pressure tube specific for microwave reactors. The suspension is degassed for a few minutes, and 0.01 mL (0.04 mmol) of trans-1,2-cyclohexanediamine is then added. The tube is then sealed and heated in the microwave reactor at 150° C. for two 1-hour cycles. After this time, the suspension cooled to room temperature is poured into 20 mL of water and then extracted with 2×30 mL of dichloromethane. The combined organic phases are dried over magnesium sulfate and concentrated under reduced pressure. The crude reaction product is then purified by chromatography on a column of silica gel, eluting with a mixture of dichloromethane and methanol. 45 mg of the expected product are thus obtained.

Workup

  1. customprepared
  2. customare placed in a 10 mL pressure tube
  3. customThe suspension is degassed for a few minutes
  4. customThe tube is then sealed
  5. temperatureAfter this time, the suspension cooled to room temperature
  6. extractionextracted with 2×30 mL of dichloromethane
  7. dry with materialThe combined organic phases are dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe crude reaction product
  10. customis then purified by chromatography on a column of silica gel
  11. washeluting with a mixture of dichloromethane and methanol

Sources & evidence

ORD record
ord-fd8c4eef48fd426f894a3e691de2f40e
Source dataset
uspto-grants-2013_03
Patent number
US08394820B2

Reaction notes

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