Potassium Carbonate → N-[2-aminopyrid-4-yl]-5-trifluoromethyl-1-[(3-fluorophenyl)methyl]-1H-pyrrolo[2,3-b]pyridine-2-carboxamide

HRID 1944005Notes

Reaction equation

HRID 1944005 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]2[CH:11]=[C:10]([C:12]([NH2:14])=[O:13])[N:9]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[C:6]2=[N:7][CH:8]=1.[NH2:25][C:26]1[CH:31]=[C:30](Br)[CH:29]=[CH:28][N:27]=1.C(=O)([O-])[O-].[K+].[K+].[C@@H]1(N)CCCC[C@H]1N>[Cu](I)I.O.O1CCOCC1>[NH2:25][C:26]1[CH:31]=[C:30]([NH:14][C:12]([C:10]2[N:9]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[C:6]3=[N:7][CH:8]=[C:3]([C:2]([F:1])([F:23])[F:24])[CH:4]=[C:5]3[CH:11]=2)=[O:13])[CH:29]=[CH:28][N:27]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 6932822-Amino-4-bromopyridineHCID 668637955-trifluoromethyl-1-[(3-fluorophenyl)methyl]-1H-pyrrolo[2,3-b]pyridine-2-carboxamide

Product 1

HCID 66863300N-[2-aminopyrid-4-yl]-5-trifluoromethyl-1-[(3-fluorophenyl)methyl]-1H-pyrrolo[2,3-b]pyridine-2-carboxamideYield 86.8%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
170 °C

Procedure

0.056 g (0.30 mmol) of copper iodide, 0.2 g (0.59 mmol) of 5-trifluoromethyl-1-[(3-fluorophenyl)methyl]-1H-pyrrolo[2,3-b]pyridine-2-carboxamide, prepared according to the protocol described in step 15.1, 0.11 g (0.65 mmol) of 2-amino-4-bromopyridine, 0.33 g (2.37 mmol) of potassium carbonate and 5 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 0.04 mL (0.33 mmol) of trans-1,2-cyclohexanediamine is then added. The tube is then sealed and heated in the microwave reactor at 170° C. for 45 minutes. After this time, the suspension cooled to room temperature is poured into 30 mL of water and then extracted with 2×40 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. 0.22 g of the expected product is thus obtained in the form of a white 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 2×40 mL of dichloromethane
  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-58348e020691449ebc5236b9d5d25a07
Source dataset
uspto-grants-2013_03
Patent number
US08394820B2

Reaction notes

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