Phenyl Methylcarbamate → 5-((2-Aminopyridin-4-yl)oxy)-6-ethoxy-N-methyl-1H-indole-1-carboxamide

HRID 1427016Notes

Reaction equation

HRID 1427016 reaction equation
[CH2:1]([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)[CH3:2].[H-].[Na+].[CH3:23][NH:24][C:25](=O)[O:26]C1C=CC=CC=1.[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C.O>[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][CH2:1][CH3:2])[N:10]([C:25]([NH:24][CH3:23])=[O:26])[CH:9]=[CH:8]3)[CH:19]=[CH:18][N:17]=1

Participants

8

Reactant 4

HCID 16034Phenyl MethylcarbamateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 867303194-((6-Ethoxy-1H-indol-5-yl)oxy)pyridin-2-amine

Product 1

HCID 867303205-((2-Aminopyridin-4-yl)oxy)-6-ethoxy-N-methyl-1H-indole-1-carboxamideYield 54%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

4-((6-Ethoxy-1H-indol-5-yl)oxy)pyridin-2-amine described in Production Example 15-6 (6.44 g, 23.9 mmol) was dissolved in N,N-dimethylformamide (80 mL), 50-72% oily sodium hydride (1.41 g) was added under nitrogen atmosphere at 0° C., and the mixture was stirred at mom temperature for 40 minutes. The mixture was cooled to 0° C. again, phenyl methylcarbamate described in Production Example 1-7 (5.78 g, 38.3 mmol) was added, and the mixture 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 and the combined organic layer was washed with water twice and then with a saturated saline solution. The organic layer was dried over anhydrous magnesium sulfate and then filtered, then the filtrate was concentrated under vacuum. A liquid mixture of diethyl ether and ethyl acetate was added to the residue, then the precipitate was collected by filteration and the resultant was washed with ethyl acetate again to obtain the title compound (4.24 g, 54%). The filtrate was purified with NH silica gel column chromatography (ethyl acetate:methanol=1:0-9:1), the target fraction was concentrated under vacuum, and then the residue was collected by filteration and washed with a liquid mixture of diethyl ether and ethyl acetate to obtain the title compound (1.58 g, 20%).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature for 3 hours
  3. customfor partition
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washthe combined organic layer was washed with water twice
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under vacuum
  9. additionA liquid mixture of diethyl ether and ethyl acetate
  10. additionwas added to the residue
  11. customthe precipitate was collected by filteration
  12. washthe resultant was washed with ethyl acetate again

Sources & evidence

ORD record
ord-68642f510fcb4dbdaad31aa4688f9b95
Source dataset
uspto-grants-2015_01
Patent number
US08933099B2

Reaction notes

Loading…