Phenyl Methylcarbamate → HCID 86730364, compound

HRID 1427063Notes

Reaction equation

HRID 1427063 reaction equation
[F:1][CH2:2][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.[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C.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][CH2:2][F:1])[N:12]([C:27]([NH:26][CH3:25])=[O:28])[CH:11]=[CH:10]3)[CH:21]=[CH:20][N:19]=1

Participants

8

Reactant 4

HCID 16034Phenyl MethylcarbamateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 86730365HCID 86730365, compound

Product 1

HCID 86730364HCID 86730364, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-((6-(3-Fluoropropoxy)-1H-indol-5-yl)oxy)pyridin-2-amine described in Production Example 33-5 (49.4 mg, 0.164 mmol) was dissolved in N,N-dimethylformamide (1.6 mL), 50-72% oily sodium hydride (14.9 mg) was added under nitrogen atmosphere at 0° C., and the mixture was stirred at room temperature for 15 minutes. The mixture was cooled to 0° C. again, phenyl methylcarbamate described in Production Example 1-7 (62.0 mg, 0.41 mmol) was added, and the mixture was stirred at room temperature for 3.5 hours. A saturated aqueous ammonium chloride solution, water, and ethyl acetate were added to the reaction mixture for partition. The organic layer was washed with a saturated saline solution and then dried over anhydrous sodium sulfate. The drying agent was filtered off, the filtrate was concentrated under vacuum, and the resultant was purified with NH silica gel column chromatography (n-heptane:ethyl acetate=1:4-0:1-ethyl acetate:methanol=99:1-9:1). The target fraction was concentrated under vacuum to obtain the title compound (34.4 mg, 59%).

Workup

  1. temperatureThe mixture was cooled to 0° C. again
  2. additionwas added
  3. stirringthe mixture was stirred at room temperature for 3.5 hours
  4. customfor partition
  5. washThe organic layer was washed with a saturated saline solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe drying agent was filtered off
  8. concentrationthe filtrate was concentrated under vacuum
  9. customthe resultant was purified with NH silica gel column chromatography (n-heptane:ethyl acetate=1:4-0:1-ethyl acetate:methanol=99:1-9:1)
  10. concentrationThe target fraction was concentrated under vacuum

Sources & evidence

ORD record
ord-462bb536240f440e9788ecceb46ed62d
Source dataset
uspto-grants-2015_01
Patent number
US08933099B2

Reaction notes

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