Water → HCID 86730329, compound

HRID 1427027Notes

Reaction equation

HRID 1427027 reaction equation
[F:1][CH:2]([F:21])[O:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][C:5]=1[O:13][C:14]1[CH:19]=[CH:18][N:17]=[C:16]([NH2:20])[CH:15]=1.[H-].[Na+].[CH3:24][NH:25][C:26](=O)[O:27]C1C=CC=CC=1.O>CN(C)C=O.C(OCC)(=O)C>[NH2:20][C:16]1[CH:15]=[C:14]([O:13][C:5]2[CH:6]=[C:7]3[C:11](=[CH:12][C:4]=2[O:3][CH:2]([F:1])[F:21])[N:10]([C:26]([NH:25][CH3:24])=[O:27])[CH:9]=[CH:8]3)[CH:19]=[CH:18][N:17]=1

Participants

7

Reactant 4

HCID 962WaterHCID 16034Phenyl MethylcarbamateHCID 24758Sodium hydrideHCID 86730330HCID 86730330, compound

Product 1

HCID 86730329HCID 86730329, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-((6-(Difluoromethoxy)-1H-indol-5-yl)oxy)pyridin-2-amine described in Production Example 19-6 (4.4 mg, 0.015 mmol) was dissolved in N,N-dimethylformamide (500 μL), then 50-72% oily sodium hydride (4.1 mg) was added under nitrogen atmosphere at 0° C., and the mixture was stirred at room temperature for 30 minutes. The mixture was cooled to 0° C. again and phenyl methylcarbamate described in Production Example 1-7 (16.4 mg, 0.108 mmol) was added, and the mixture was stirred at room temperature for 50 minutes. Water and ethyl acetate were added to the reaction mixture for partition. The organic layer was washed with a saturated saline solution, then dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under vacuum. The residue was dissolved in dichloromethane and the resultant was purified with NH silica gel column chromatography (n-heptane:ethyl acetate=1:1-0:1-ethyl acetate:methanol=99:1-9:1), and then the target fraction was concentrated under vacuum to obtain the title compound (4.3 mg, 82%).

Workup

  1. temperatureThe mixture was cooled to 0° C. again
  2. additionwas added
  3. stirringthe mixture was stirred at room temperature for 50 minutes
  4. customfor partition
  5. washThe organic layer was washed with a saturated saline solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under vacuum
  9. dissolutionThe residue was dissolved in dichloromethane
  10. customthe resultant was purified with NH silica gel column chromatography (n-heptane:ethyl acetate=1:1-0:1-ethyl acetate:methanol=99:1-9:1)
  11. concentrationthe target fraction was concentrated under vacuum

Sources & evidence

ORD record
ord-81e82a3f1f4c46398704691a59b12e30
Source dataset
uspto-grants-2015_01
Patent number
US08933099B2

Reaction notes

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