Ethyl Acetate → 5-((2-Aminopyridin-4-yl)oxy)-6-(2-methoxyethoxy)-N-methyl-1H-indole-1-carboxamide

HRID 1427033Notes

Reaction equation

HRID 1427033 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([CH:10]=[CH:11][NH:12]2)=[CH:8][C:7]=1[O:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]([NH2:22])[CH:17]=1.[H-].[Na+].[CH3:25][NH:26][C:27](=O)[O:28]C1C=CC=CC=1.C(OCC)(=O)C>CN(C)C=O.O>[NH2:22][C:18]1[CH:17]=[C:16]([O:15][C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][C:6]=2[O:5][CH2:4][CH2:3][O:2][CH3:1])[N:12]([C:27]([NH:26][CH3:25])=[O:28])[CH:11]=[CH:10]3)[CH:21]=[CH:20][N:19]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 16034Phenyl MethylcarbamateHCID 24758Sodium hydrideHCID 867303354-((6-(2-Methoxyethoxy)-1H-indol-5-yl)oxy)pyridin-2-amine

Product 1

HCID 867303365-((2-Aminopyridin-4-yl)oxy)-6-(2-methoxyethoxy)-N-methyl-1H-indole-1-carboxamideYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-((6-(2-Methoxyethoxy)-1H-indol-5-yl)oxy)pyridin-2-amine described in Production Example 20-6 (2.60 g, 8.67 mmol) was dissolved in N,N-dimethylformamide (50 mL), then 50-72% oily sodium hydride (499 mg) was added under nitrogen atmosphere at room temperature. Phenyl methylcarbamate described in Production Example 1-7 (1.97 g, 13.0 mmol) was added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was cooled to 0° C. and ethyl acetate and water were added for partition. The aqueous layer was extracted with ethyl acetate twice, sodium chloride was added to the aqueous layer, and the resultant was extracted with ethyl acetate three times. The combined organic layer was dried over anhydrous sodium sulfate. The drying agent was filtered off and the filtrate was concentrated under vacuum, and then the resultant was purified with NH silica gel column chromatography (n-heptane:ethyl acetate=1:4-0:1-ethyl acetate:methanol=49:1-24:1). The target fraction was concentrated under vacuum, and ethyl acetate was added and the precipitate was collected by filteration and washed to obtain the title compound (2.23 g, 72%).

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. customfor partition
  4. extractionThe aqueous layer was extracted with ethyl acetate twice
  5. additionsodium chloride was added to the aqueous layer
  6. extractionthe resultant was extracted with ethyl acetate three times
  7. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  8. filtrationThe drying agent was filtered off
  9. concentrationthe filtrate was concentrated under vacuum
  10. customthe resultant was purified with NH silica gel column chromatography (n-heptane:ethyl acetate=1:4-0:1-ethyl acetate:methanol=49:1-24:1)
  11. concentrationThe target fraction was concentrated under vacuum, and ethyl acetate
  12. additionwas added
  13. customthe precipitate was collected by filteration
  14. washwashed

Sources & evidence

ORD record
ord-4e105653225f436a87b8fd9194e5f9bf
Source dataset
uspto-grants-2015_01
Patent number
US08933099B2

Reaction notes

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