Ammonium Hydroxide → 3-Ethoxy-5-methoxy-1-phenyl-1H-indole-2-carboxamide

HRID 21591Notes

Reaction equation

HRID 21591 reaction equation
[CH2:1]([O:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:5]=1[C:21]([OH:23])=O)[CH3:2].C(N1C=CN=C1)([N:26]1C=CN=C1)=O.[OH-].[NH4+]>O1CCCC1>[CH2:1]([O:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:5]=1[C:21]([NH2:26])=[O:23])[CH3:2]

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 13885793HCID 13885793, compound

Product 1

HCID 152945313-Ethoxy-5-methoxy-1-phenyl-1H-indole-2-carboxamideYield 75.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-ethoxy-5-methoxy-1-phenyl-1H-indole-2-carboxylic acid (0.11 g, 0.35 mmol; Unangst PC, et al., J. Med. Chem. 1989;32:1360) and 1,1'-carbonyldiimidazole (0.065 g, 0.40 mmol) in 5.0 mL of tetrahydrofuran is stirred at reflux for 90 minutes. The mixture is cooled slightly and 5.0 mL of concentrated ammonium hydroxide is added. After stirring for an additional 90 minutes, the mixture is partitioned between ethyl acetate and brine. The organic layer is washed several times with fresh brine, dried (anhydrous sodium sulfate) and evaporated. Recrystallization of the residue from ethyl acetate-hexane yields 0.082 g (75%) of product; mp 143°-144° C.

Workup

  1. temperatureat reflux for 90 minutes
  2. temperatureThe mixture is cooled slightly
  3. stirringAfter stirring for an additional 90 minutes
  4. customthe mixture is partitioned between ethyl acetate and brine
  5. washThe organic layer is washed several times with fresh brine
  6. dry with materialdried (anhydrous sodium sulfate)
  7. customevaporated
  8. customRecrystallization of the residue from ethyl acetate-hexane

Sources & evidence

ORD record
ord-d7b95a21649e4dc9b856b76737e05073
Source dataset
uspto-grants-1995_06
Patent number
US05424329

Reaction notes

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