Sodium methanethiolate → 5-Chloro-N-[1-[2-(methylthio)ethyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-1H-indole-2-carboxamide

HRID 1376143Notes

Reaction equation

HRID 1376143 reaction equation
[CH3:1][S-:2].[Na+].[Cl:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]([C:14]([NH:16][CH:17]1[CH2:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]([CH2:27][CH2:28]Cl)[C:18]1=[O:30])=[O:15])=[CH:8]2>CN(C=O)C.CCOC(C)=O>[Cl:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]([C:14]([NH:16][CH:17]1[CH2:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]([CH2:27][CH2:28][S:2][CH3:1])[C:18]1=[O:30])=[O:15])=[CH:8]2

Participants

5

Reactant 2

HCID 4378561Sodium methanethiolateHCID 587884525-chloro-N-[1-(2-chloroethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-1H-indole-2-carboxamide

Product 1

HCID 101945055-Chloro-N-[1-[2-(methylthio)ethyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-1H-indole-2-carboxamideYield 37.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Sodium thiomethoxide (280 mg, 4.00 mmol) and KI (10 mg, 0.06 mmol) were added to a soluton of 5-chloro-N-[1-(2-chloroethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-1H-indole-2-carboxamide (Method 3; 1.07 g, 2.67 mmol) in DMF (10 mL) under an inert atmosphere and heated at 80° C. for 2 hours. On cooling the mixture was diluted with EtOAc (100 mL), washed with water (20 mL), dried (Na2SO4), filtered and evaporated. The residue was purified by column chromatography (DCM to DCM:THF (2:23)) to give a white solid. The solid was triturated with refluxing Et2O (20 mL) and the solid filtered, washed with Et2O (10 mL) then hexane (10 mL) to afford the title compound (410 mg, 37%) as an off white solid.

Workup

  1. temperatureOn cooling the mixture
  2. washwashed with water (20 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography (DCM to DCM:THF (2:23))
  7. customto give a white solid
  8. customThe solid was triturated with refluxing Et2O (20 mL)
  9. filtrationthe solid filtered
  10. washwashed with Et2O (10 mL)

Sources & evidence

ORD record
ord-b5ab8dd6c7204ea9806a9f225baba0a8
Source dataset
uspto-grants-2007_01
Patent number
US07169927B2

Reaction notes

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