Water → 5-Methoxy-1-methyl-3-(1-methylethoxy)-1H-indole-2-carboxamide

HRID 21578Notes

Reaction equation

HRID 21578 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[C:7]([C:13](O)=[O:14])=[C:6]2[O:16][CH:17]([CH3:19])[CH3:18].C(N1C=CN=C1)([N:22]1C=CN=C1)=O.[OH-].[NH4+].O>C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[C:7]([C:13]([NH2:22])=[O:14])=[C:6]2[O:16][CH:17]([CH3:19])[CH3:18]

Participants

6

Reactant 4

HCID 962WaterHCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 138857995-Methoxy--methyl-3-(1-methylethoxy)-1H-indole-2-carboxylic acid

Product 1

HCID 102208805-Methoxy-1-methyl-3-(1-methylethoxy)-1H-indole-2-carboxamideYield 53.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 5-methoxy-1-methyl-3-(1-methylethoxy)-1H-indole-2-carboxylic acid (4.0 g, 15 mmol; Unangst PC, et al., J. Med. Chem. 1989;32:1360) and 1,1'-carbonyldiimidazole (2.6 g, 16 mmol) in 75 mL of acetonitrile is stirred at reflux for 2 hours. The mixture is cooled slightly and 75 mL of concentrated ammonium hydroxide is added. After stirring for 15 minutes, the mixture is added to 600 g of ice and water. The precipitated solid is filtered, washed with water, and recrystallized from aqueous acetonitrile to give 2.1 g (53%) of product; mp 147°-149° C.

Workup

  1. temperatureat reflux for 2 hours
  2. temperatureThe mixture is cooled slightly
  3. stirringAfter stirring for 15 minutes
  4. filtrationThe precipitated solid is filtered
  5. washwashed with water
  6. customrecrystallized from aqueous acetonitrile

Sources & evidence

ORD record
ord-42b62a9fafc944d5b7d487f349339f77
Source dataset
uspto-grants-1995_06
Patent number
US05424329

Reaction notes

Loading…