Dimethyl Sulfoxide → N-(4-((6-(2-Ethoxyethoxy)-1H-indol-5-yl)oxy)pyridin-2-yl)acetamide

HRID 1427039Notes

Reaction equation

HRID 1427039 reaction equation
CS(C)=O.[CH2:5]([O:7][CH2:8][CH2:9][O:10][C:11]1[CH:19]=[C:18]2[C:14]([CH:15]=[CH:16][NH:17]2)=[CH:13][C:12]=1[OH:20])[CH3:6].Cl[C:22]1[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29](=[O:31])[CH3:30])[CH:23]=1.CC(C)([O-])C.[K+]>O.C(OCC)(=O)C>[CH2:5]([O:7][CH2:8][CH2:9][O:10][C:11]1[CH:19]=[C:18]2[C:14]([CH:15]=[CH:16][NH:17]2)=[CH:13][C:12]=1[O:20][C:22]1[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29](=[O:31])[CH3:30])[CH:23]=1)[CH3:6]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 22832129N-(4-Chloropyridin-2-yl)acetamideHCID 23665647Potassium tert-butoxideHCID 867303416-(2-Ethoxyethoxy)-1H-indol-5-ol

Product 1

HCID 86730342N-(4-((6-(2-Ethoxyethoxy)-1H-indol-5-yl)oxy)pyridin-2-yl)acetamideYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

Dimethylsulfoxide (20 mL) was added to a mixture of 6-(2-ethoxyethoxy)-1H-indol-5-ol described in Production Example 24-5 (3.28 g, 14.8 mmol), N-(4-chloropyridin-2-yl)acetamide described in Production Example 1-5 (2.78 g, 16.3 mmol), and potassium tert-butoxide (1.83 g, 16.3 mmol) under nitrogen atmosphere at room temperature. The liquid mixture was stirred at 150° C. overnight. The reaction liquid was allowed to stand to cool to room temperature and then diluted with water and ethyl acetate. The organic layer was washed with a saturated saline solution and dried over anhydrous sodium sulfate, and then the drying agent was separated by filtration. The filtrate was concentrated under vacuum. The residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=1:1-0:1-ethyl acetate:methanol=99:1-19:1) to obtain the title compound (2.5 g, 48%).

Workup

  1. customThe reaction liquid
  2. temperatureto cool to room temperature
  3. washThe organic layer was washed with a saturated saline solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe drying agent was separated by filtration
  6. concentrationThe filtrate was concentrated under vacuum
  7. customThe residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=1:1-0:1-ethyl acetate:methanol=99:1-19:1)

Sources & evidence

ORD record
ord-9cd462329aa84014b77b2e0e837efd04
Source dataset
uspto-grants-2015_01
Patent number
US08933099B2

Reaction notes

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