Phenyl Methylcarbamate → HCID 86730313, compound

HRID 1426994Notes

Reaction equation

HRID 1426994 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[CH:8][NH:9]2)=[CH:5][C:4]=1[O:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[CH:14]=1.[H-].[Na+].[CH3:22][NH:23][C:24](=O)[O:25]C1C=CC=CC=1.[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C.O>[NH2:19][C:15]1[CH:14]=[C:13]([O:12][C:4]2[CH:5]=[C:6]3[C:10](=[CH:11][C:3]=2[O:2][CH3:1])[N:9]([C:24]([NH:23][CH3:22])=[O:25])[CH:8]=[CH:7]3)[CH:18]=[CH:17][N:16]=1

Participants

8

Reactant 4

HCID 16034Phenyl MethylcarbamateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 86730314HCID 86730314, compound

Product 1

HCID 86730313HCID 86730313, compoundYield 66%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-((6-Methoxy-1H-indol-5-yl)oxy)pyridin-2-amine described in Production Example 1-4 (1.7 g, 6.66 mmol) was dissolved in N,N-dimethylformamide (25 mL), 50-72% oily sodium hydride (424 mg) was added under nitrogen atmosphere at 0° C., and then the mixture was stirred at room temperature for 45 minutes. The mixture was cooled to 0° C. again, phenyl methylcarbamate described in Production Example 1-7 (1.64 g, 10.8 mmol) was added, and the resultant was stirred at room temperature for 3 hours. A saturated aqueous ammonium chloride solution, water, and ethyl acetate were added to the reaction mixture for partition. The aqueous layer was extracted with ethyl acetate once and the combined organic layer was washed with water and a saturated saline solution. The organic layer was dried over anhydrous magnesium sulfate. The drying agent was filtered off, then the filtrate was concentrated under vacuum, and then the resultant was purified with NH silica gel column chromatography (n-heptane:ethyl acetate=1:3-0:1-ethyl acetate:methanol=99:1-19:1). The target fraction was concentrated under vacuum and then the precipitate was collected by filteration and washed with ethyl acetate to obtain the title compound (1.37 g, 66%). The mixture fraction was concentrated under vacuum and purified with NH silica gel column chromatography (n-heptane:ethyl acetate=3:7-0:1-ethyl acetate:methanol—99:1-19:1). The target fraction was concentrated under vacuum, and then the precipitate was collected by filteration and washed with ethyl acetate twice to obtain the title compound (387 mg, 19%).

Workup

  1. temperatureThe mixture was cooled to 0° C. again
  2. additionwas added
  3. stirringthe resultant was stirred at room temperature for 3 hours
  4. customfor partition
  5. extractionThe aqueous layer was extracted with ethyl acetate once
  6. washthe combined organic layer was washed with water
  7. dry with materialThe organic layer was dried over anhydrous magnesium 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=1:3-0:1-ethyl acetate:methanol=99:1-19:1)
  11. concentrationThe target fraction was concentrated under vacuum
  12. customthe precipitate was collected by filteration
  13. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-64f1c16e5fe74c3ea8444ba800ee130e
Source dataset
uspto-grants-2015_01
Patent number
US08933099B2

Reaction notes

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