Phenyl Methylcarbamate → N1-Methyl-5-(2-amino-4-pyridyl)oxy-1H-1-indolecarboxamide

HRID 2215498Notes

Reaction equation

HRID 2215498 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([O:12][C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[CH:14]=3)=[CH:9][CH:10]=2)[CH:5]=[CH:4]1.[CH3:20][NH:21][C:22](=O)[O:23]C1C=CC=CC=1>CN(C)C=O>[CH3:20][NH:21][C:22]([N:3]1[C:11]2[C:6](=[CH:7][C:8]([O:12][C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[CH:14]=3)=[CH:9][CH:10]=2)[CH:5]=[CH:4]1)=[O:23]

Participants

5

Reactant 3

HCID 16034Phenyl MethylcarbamateHCID 24758Sodium hydrideHCID 219493654-(1H-5-indolyloxy)-2-pyridinamine

Product 1

HCID 21949141N1-Methyl-5-(2-amino-4-pyridyl)oxy-1H-1-indolecarboxamideYield 76.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (430 mg, 10.75 mmol) was suspended in N,N-dimethylformamide (25 ml) under nitrogen atmosphere, and 4-(1H-5-indolyloxy)-2-pyridinamine (2.253 g, 10.00 mmol, CAS No. 417722-11-3) described in WO 02/32872 was gradually added while stirred at room temperature. After 10 minutes, the reaction mixture was cooled with an ice water bath, and then phenyl N-methylcarbamate (1.587 g, 10.50 mmol) was added. The reaction mixture was heated to room temperature and stirred for 2 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water and brine, and was dried over anhydrous sodium sulfate. The solvent was removed by distilled off. The crystals were precipitated from ethyl acetate, filtered off, and dried under aeration to yield the title compound (2.163 g, 7.66 mmol, 76.6%) as pale brown crystals.

Workup

  1. additionwas gradually added
  2. temperaturethe reaction mixture was cooled with an ice water bath
  3. temperatureThe reaction mixture was heated to room temperature
  4. stirringstirred for 2 hours
  5. customThe reaction mixture was partitioned between ethyl acetate and water
  6. washThe organic layer was washed with water and brine
  7. dry with materialwas dried over anhydrous sodium sulfate
  8. customThe solvent was removed
  9. distillationby distilled off
  10. customThe crystals were precipitated from ethyl acetate
  11. filtrationfiltered off
  12. customdried under aeration

Sources & evidence

ORD record
ord-e8427cd3b745407ea445224238d1ad13
Source dataset
uspto-grants-2006_09
Patent number
US07109219B2

Reaction notes

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