Chloroform → Ethyl 2-(4-(3-(2-chlorobenzoyl)-5-methylthiophen-2-yl)-5-methyl[1,2,4]triazol-3-ylmethylcarbamoyl)indole-1-acetate

HRID 963066

Reaction equation

HRID 963066 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([CH3:18])[S:17][C:13]=2[N:12]2[C:19]([CH3:22])=[N:20][N:21]=[C:11]2[CH2:10][N:9]=1.C(Cl)(Cl)Cl.C(=O)([O-])[OH:28].[Na+].[CH2:32]([O:34][C:35]([CH2:37][N:38]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:40]=[C:39]1[C:47](Cl)=[O:48])=[O:36])[CH3:33]>Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([C:14]1[CH:15]=[C:16]([CH3:18])[S:17][C:13]=1[N:12]1[C:19]([CH3:22])=[N:20][N:21]=[C:11]1[CH2:10][NH:9][C:47]([C:39]1[N:38]([CH2:37][C:35]([O:34][CH2:32][CH3:33])=[O:36])[C:46]2[C:41]([CH:40]=1)=[CH:42][CH:43]=[CH:44][CH:45]=2)=[O:48])=[O:28]

Participants

6

Reactant 4

HCID 6212ChloroformHCID 516892Sodium BicarbonateHCID 124343244-(2-Chlorophenyl)-2,9-dimethyl-6H-thieno[3,2-f] [1,2,4]triazolo[4,3-a] [1,4]diazepineHCID 190851631-Ethoxycarbonylmethylindole-2-carbonyl chloride

Product 1

HCID 22439218Ethyl 2-(4-(3-(2-chlorobenzoyl)-5-methylthiophen-2-yl)-5-methyl[1,2,4]triazol-3-ylmethylcarbamoyl)indole-1-acetateYield 85.7%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
60 °C

Procedure

4-(2-Chlorophenyl)-2,9-dimethyl-6H-thieno[3,2-f] [1,2,4]triazolo[4,3-a] [1,4]diazepine (4.15 g) was dissolved in 5% hydrochloric acid (50 ml), and the solution was stirred at 60° C. for 4 hours. The reaction mixture was cooled in a water bath, and chloroform (60 ml) and sodium hydrogencarbonate (12.6 g) were added with vigorous stirring. Then, 1-ethoxycarbonylmethylindole-2-carbonyl chloride (3.52 g) was added, and the mixture was stirred for 1 hour. The chloroform layer was washed with saturated brine and dried over magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography using a mixed solvent of ethyl acetate and methanol as eluent and crystallized from a mixed solvent of ethyl acetate and hexane to give 6.23 g of ethyl 2-(4-(3-(2-chlorobenzoyl)-5-methylthiophen-2-yl)-5-methyl[1,2,4]triazol-3-ylmethylcarbamoyl)indole-1-acetate.

Workup

  1. temperatureThe reaction mixture was cooled in a water bath
  2. stirringthe mixture was stirred for 1 hour
  3. washThe chloroform layer was washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was evaporated
  6. customthe residue was purified by silica gel column chromatography
  7. customcrystallized from a mixed solvent of ethyl acetate and hexane

Sources & evidence

ORD record
ord-0b71b69418774cd3a9613a0c3385e719
Source dataset
uspto-grants-1998_06
Patent number
US05760032

Linked notes

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