Diethyl Oxalate → Ethyl [2-({7-(benzyloxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indol-2-yl}carbonyl)hydrazino](oxo)acetate

HRID 1188891Notes

Reaction equation

HRID 1188891 reaction equation
O.NN.[C:4]([O:11][CH2:12][CH3:13])(=[O:10])[C:5]([O:7]CC)=O.[CH2:14]([O:21][C:22]1[CH:23]=[C:24]([O:34][C:35]2[CH:40]=[CH:39][C:38]([S:41]([CH3:44])(=[O:43])=[O:42])=[CH:37][CH:36]=2)[CH:25]=[C:26]2[C:30]=1[NH:29][C:28]([C:31](O)=[O:32])=[CH:27]2)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl.CN(C)CCCN=C=NCC.O[N:58]1C2C=CC=CC=2N=[N:59]1>C(O)C.CCCCCC.C(OCC)(=O)C.O.CN(C)C=O>[CH2:14]([O:21][C:22]1[CH:23]=[C:24]([O:34][C:35]2[CH:36]=[CH:37][C:38]([S:41]([CH3:44])(=[O:42])=[O:43])=[CH:39][CH:40]=2)[CH:25]=[C:26]2[C:30]=1[NH:29][C:28]([C:31]([NH:58][NH:59][C:5](=[O:7])[C:4]([O:11][CH2:12][CH3:13])=[O:10])=[O:32])=[CH:27]2)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

11

Reactant 5

HCID 7268Diethyl OxalateHCID 24654Hydrazine hydrate (1:1)HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 668975467-(Benzyloxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylic acid

Product 1

HCID 66897270Ethyl [2-({7-(benzyloxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indol-2-yl}carbonyl)hydrazino](oxo)acetateYield 83%

Reagents, catalysts & solvents 5

HCID 702EthanolSolvent2×HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of hydrazine monohydrate (0.1 mL) in ethanol (2 mL) was added dropwise to a solution of diethyl oxalate (0.3 mL) in ethanol (2 mL) under ice-cooling. The reaction mixture was concentrated under reduced pressure to give a white solid. A mixture of 7-(benzyloxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylic acid (450 mg), 1-[3-(dimethylamino)propyl-3-ethylcarbodiimide hydrochloride (403 mg), 1-hydroxybenzotriazole (284 mg) and N,N-dimethylformamide (20 mL) was stirred at room temperature for 30 min, the previous-obtained white solid was added, and the mixture was stirred at room temperature for 2 hr. Water was added to the reaction solution, and the mixture was subjected to extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtrated, and concentrated under reduced pressure. The obtained crude product was subjected to silica gel column chromatography (ethyl acetate:hexane=20:80-90:10, volume ratio) to give the title compound (420 mg, yield 83%) as an orange oil. MS 552 (MH+).

Workup

  1. temperaturecooling
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customto give a white solid
  4. additionthe previous-obtained white solid was added
  5. stirringthe mixture was stirred at room temperature for 2 hr
  6. extractionthe mixture was subjected to extraction with ethyl acetate
  7. washThe organic layer was washed with saturated brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltrated
  10. concentrationconcentrated under reduced pressure
  11. customThe obtained crude product

Sources & evidence

ORD record
ord-2101a507ae0c47ba971d0f4dd294fd04
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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