Ammonium Hydroxide → 7-[2-Methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxamide

HRID 1188914Notes

Reaction equation

HRID 1188914 reaction equation
[CH3:1][O:2][CH2:3][CH:4]([CH2:29][O:30][CH3:31])[O:5][C:6]1[CH:7]=[C:8]([O:18][C:19]2[CH:20]=[N:21][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:23][CH:24]=2)[CH:9]=[C:10]2[C:14]=1[NH:13][C:12]([C:15](O)=[O:16])=[CH:11]2.Cl.C([N:35]=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[OH-].[NH4+]>CN(C)C=O>[CH3:31][O:30][CH2:29][CH:4]([CH2:3][O:2][CH3:1])[O:5][C:6]1[CH:7]=[C:8]([O:18][C:19]2[CH:20]=[N:21][C:22]([S:25]([CH3:28])(=[O:26])=[O:27])=[CH:23][CH:24]=2)[CH:9]=[C:10]2[C:14]=1[NH:13][C:12]([C:15]([NH2:35])=[O:16])=[CH:11]2

Participants

6

Reactant 4

HCID 14923Ammonium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 668979397-[2-Methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxylic acid

Product 1

HCID 668974087-[2-Methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxamideYield 106.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 7-[2-methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxylic acid (1.02 g), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (868 mg), 1-hydroxybenzotriazole (612 mg) and N,N-dimethylformamide (20 mL) was stirred at 50° C. for 25 min. The mixture was cooled to room temperature, and 10% ammonium hydroxide solution (3 mL) was added to the mixture. After stirring at room temperature for 2 days, the mixture was concentrated under reduced pressure. Water was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over magnesium sulfate, filtered and concentrated to give the title compound (1.08 g, 100%) as an orange oil. MS 450 (MH+).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. stirringAfter stirring at room temperature for 2 days
  3. concentrationthe mixture was concentrated under reduced pressure
  4. additionWater was added to the residue
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed successively with water and saturated brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-2e178d95252947c4b1f25a1ce4578216
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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