Potassium Carbonate → N-[2-aminopyrid-4-yl]-5-fluoro-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxamide

HRID 1944000Notes

Reaction equation

HRID 1944000 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.[NH2:22][C:23]1[CH:28]=[C:27](Br)[CH:26]=[CH:25][N:24]=1.C(=O)([O-])[O-].[K+].[K+].[C@@H]1(N)CCCC[C@H]1N>[Cu](I)I.O.O1CCOCC1>[NH2:22][C:23]1[CH:28]=[C:27]([NH:21][C:19]([C:6]2[N:7]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)[C:8]3[C:4]([CH:5]=2)=[CH:3][C:2]([F:1])=[CH:10][CH:9]=3)=[O:20])[CH:26]=[CH:25][N:24]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 6932822-Amino-4-bromopyridineHCID 668456965-Fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamide

Product 1

HCID 66863747N-[2-aminopyrid-4-yl]-5-fluoro-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxamideYield 53.5%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
170 °C

Procedure

0.2 g (1.05 mmol) of copper iodide, 0.6 g (2.10 mmol) of 5-fluoro-1-[(3-fluorophenyl)-methyl]-1H-indole-2-carboxamide, prepared according to the protocol described in step 1.2, 0.4 g (2.31 mmol) of 2-amino-4-bromopyridine, 1.16 g (8.40 mmol) of potassium carbonate and 15 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 0.14 mL (1.15 mmol) of trans-1,2-cyclohexanediamine is then added. The tube is then sealed and heated in the microwave reactor at 170° C. for two 1-hour cycles, After this time, the suspension cooled to room temperature is poured into 50 mL of water and then extracted with 2×75 mL of dichlororomethane. 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. 0.425 g of the expected product is thus obtained in the form of a beige-coloured solid.

Workup

  1. customare placed in a 10 mL pressure tube
  2. customThe suspension is degassed for a few minutes
  3. customThe tube is then sealed
  4. temperatureAfter this time, the suspension cooled to room temperature
  5. extractionextracted with 2×75 mL of dichlororomethane
  6. dry with materialThe combined organic phases are dried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude reaction product
  9. customis then purified by chromatography on a column of silica gel
  10. washeluting with a mixture of dichloromethane and methanol

Sources & evidence

ORD record
ord-467081f127a94d57a7bb7bddc0ae46b8
Source dataset
uspto-grants-2013_03
Patent number
US08394820B2

Reaction notes

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