1-Methylindole → HCID 18985206, compound

HRID 1440037Notes

Reaction equation

HRID 1440037 reaction equation
Cl.C(N(CC)[C:5]([CH:7]1[CH2:15][CH2:14][C:10]2[N:11]=[CH:12][NH:13][C:9]=2[CH2:8]1)=[O:6])C.[CH3:18][N:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[CH:20]1.P(Cl)(Cl)(Cl)=O.[OH-].[Na+].[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39].C([O-])(=O)/C=C/C([O-])=O>O>[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39].[CH3:18][N:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]([C:5]([CH:7]2[CH2:15][CH2:14][C:10]3[N:11]=[CH:12][NH:13][C:9]=3[CH2:8]2)=[O:6])=[CH:20]1

Participants

8

Reactant 6

HCID 117811-MethylindoleHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 444972Fumaric AcidHCID 5460307FumarateHCID 18985214HCID 18985214, compound

Product 1

HCID 18985206HCID 18985206, compoundYield 29.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 0.27 g (1.05 mmol) of N,N-diethyl 4,5,6,7-tetrahydrobenzimidazole-5-carboxamide hydrochloride, 0.16 ml (1.25 mmol) of 1-methylindole, and 0.15 ml (1.65 mmol) of phosphorus oxychloride was heated at 80° C. for 2 hours while stirring. 30 ml of water were added thereto, and the mixture was rendered basic with a 1N sodium hydroxide aqueous solution, followed by extracting with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was distilled under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane/methanol/aqueous ammonia=10:1:0.1 by volume) and preparative thin layer chromatography (developing solvent: dichloromethane/methanol/aqueous ammonia=10:1:0.1 by volume) to obtain 20 mg of a foaming substance. To the product was added 10 mg of fumaric acid to convert it to a fumarate. Recrystallization from ethyl acetate/methanol (10:1 by volume) gave 10 mg of 5-[(1-methylindol-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole fumarate.

Workup

  1. extractionby extracting with ethyl acetate
  2. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. distillationThe filtrate was distilled under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (eluent: dichloromethane/methanol/aqueous ammonia=10:1:0.1 by volume) and preparative thin layer chromatography (developing solvent: dichloromethane/methanol/aqueous ammonia=10:1:0.1 by volume)
  6. customto obtain 20 mg of a foaming substance
  7. customRecrystallization from ethyl acetate/methanol (10:1 by volume)

Sources & evidence

ORD record
ord-6d9b7cd64bea4d25be9da643a7e0fc26
Source dataset
uspto-grants-1996_03
Patent number
US05496942

Reaction notes

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