Pyridine → Phenyl N-(4-(1-(methylamino)carbonyl-1H-5-indolyl)oxy-2-pyridyl)carbamate

HRID 2215514Notes

Reaction equation

HRID 2215514 reaction equation
[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH2:21])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4].N1C=CC=CC=1.C(N(CC)CC)C.[C:35](Cl)(=[O:43])[O:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>CN(C)C=O>[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:35](=[O:43])[O:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4]

Participants

6

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 21949141N1-Methyl-5-(2-amino-4-pyridyl)oxy-1H-1-indolecarboxamide

Product 1

HCID 21949226Phenyl N-(4-(1-(methylamino)carbonyl-1H-5-indolyl)oxy-2-pyridyl)carbamateYield 88.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N1-Methyl-5-(2-amino-4-pyridyl)oxy-1H-1-indolecarboxamide (2.163 g, 7.66 mmol) synthesized in Production example 5-1 was dissolved in N,N-dimethylformamide (50 ml) under nitrogen atmosphere; pyridine (0.93 ml, 11.5 mmol), triethylamine (2.4 ml, 17.24 mmol) and phenyl chlorocarbonate (1.44 ml, 11.5 mmol) were sequentially added dropwise while cooled with an ice water bath; and the reaction mixture was heated to room temperature while stirred. After 1 hour, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was distilled off, and then the residue was purified by silica gel column chromatography (eluent; ethyl acetate), precipitated from ethyl acetate-hexane (1:10), filtered off, and dried under aeration to yield the title compound (2.731 g, 6.79 mmol, 88.6%) as white crystals.

Workup

  1. temperaturewhile cooled with an ice water bath
  2. customthe reaction mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off
  6. customthe residue was purified by silica gel column chromatography (eluent; ethyl acetate)
  7. customprecipitated from ethyl acetate-hexane (1:10)
  8. filtrationfiltered off
  9. customdried under aeration

Sources & evidence

ORD record
ord-a2cdfed120c54ecd87b46687873e73fd
Source dataset
uspto-grants-2006_09
Patent number
US07109219B2

Reaction notes

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