Methyl propiolate → Ethyl 3-(4-bromo-7-carbamoyl-1H-indol-3-yl)-2-nitropropanoate

HRID 2361434Notes

Reaction equation

HRID 2361434 reaction equation
C(OC)(=O)C#C.[Br:7][C:8]1[CH:16]=[CH:15][C:14]([C:17]([NH2:19])=[O:18])=[C:13]2[C:9]=1[C:10]([CH2:20]N(C)C)=[CH:11][NH:12]2.[N+:24]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])([O-:26])=[O:25]>ClCCl.C(#N)C>[Br:7][C:8]1[CH:16]=[CH:15][C:14]([C:17](=[O:18])[NH2:19])=[C:13]2[C:9]=1[C:10]([CH2:20][CH:27]([N+:24]([O-:26])=[O:25])[C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:11][NH:12]2

Participants

6

Reactant 3

HCID 13536Methyl propiolateHCID 69379Ethyl nitroacetateHCID 679948144-Bromo-3-((dimethylamino)methyl)-1H-indole-7-carboxamide

Product 1

HCID 86681529Ethyl 3-(4-bromo-7-carbamoyl-1H-indol-3-yl)-2-nitropropanoateYield 57%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl propiolate (2.300 mL, 27.5 mmol) was added slowly to a suspension of crude 4-bromo-3-((dimethylamino)methyl)-1H-indole-7-carboxamide (6.27 g, 21.17 mmol) and ethyl 2-nitroacetate (3.66 g, 27.5 mmol) in dichloromethane (151 mL) and acetonitrile (151 mL). After 30 min, the mixture was concentrated and partitioned between EtOAc and 1 M aqueous HCl. The organic phase was washed with NaHCO3 (aq) and brine, dried and concentrated. The residue was coated subjected to column chromatography on silica gel (80 g), eluting with EtOAc-hexane (gradient from 50:50 to 80:20) to provide the desired product as a solid (4.60 g, 57% yield). LCMS (M+H)+ m/z 383.8, 385.8.

Workup

  1. concentrationthe mixture was concentrated
  2. custompartitioned between EtOAc and 1 M aqueous HCl
  3. washThe organic phase was washed with NaHCO3 (aq) and brine
  4. customdried
  5. concentrationconcentrated
  6. washeluting with EtOAc-hexane (gradient from 50:50 to 80:20)

Sources & evidence

ORD record
ord-89106c1f1f794f118dcbc0f2c5235fc7
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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