Methyl isothiocyanate → N-Methyl-1-(2-methylimidazo[1,2-a]pyridin-6-yl)-2-oxocyclohexanecarbothioamide

HRID 1757116Notes

Reaction equation

HRID 1757116 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][C:11]3=[O:16])=[CH:6][N:5]2[CH:17]=1.CC(C)([O-])C.[K+].[CH3:24][N:25]=[C:26]=[S:27].[Cl-].[NH4+]>O1CCCC1.CN(C)C=O>[CH3:24][NH:25][C:26]([C:10]1([C:7]2[CH:8]=[CH:9][C:4]3[N:5]([CH:17]=[C:2]([CH3:1])[N:3]=3)[CH:6]=2)[CH2:15][CH2:14][CH2:13][CH2:12][C:11]1=[O:16])=[S:27]

Participants

7

Reactant 4

HCID 11167Methyl isothiocyanateHCID 25517Ammonium ChlorideHCID 15341314HCID 15341314, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 19972896N-Methyl-1-(2-methylimidazo[1,2-a]pyridin-6-yl)-2-oxocyclohexanecarbothioamideYield 78.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

In a nitrogen atmosphere, a solution of 35.79 g (0.157 mol) of the 2-(2-methylimidazo[1,2-a]pyridin-6-yl)cyclohexanone prepared in the Preparative Example 2 in 550 ml of tetrahydrofuran was cooled with ice, followed by the addition of 19.55 g (0.174 mol) of potassium t-butoxide. The obtained yellow solution was stirred under cooling with ice for one hour, followed by the addition of a solution of 11.8 ml (0.173 mol) of methyl isothiocyanate in 50 ml of tetrahydrofuran and 50 ml of N,N-dimethylformamide in this order. The obtained reaction mixture was stirred under cooling with ice for one hour, followed by the addition of a saturated aqueous solution of ammonium chloride. The obtained mixture was extracted with chloroform. The organic phase was washed with a saturated aqueous solution of common salt, dried over anhydrous magnesium sulfate, and concentrated in a vacuum. In the course of the concentration, a crystal began to precipitate. This crystal was recovered by filtration. 37.09 g of the title compound was obtained as a colorless crystal. Further, the mother liquor (14.5 g) was purified by silica gel column chromatography [solvent: dichloromethane/methanol (100:3)] and recrystallized from dichloromethane/ethyl acetate to give 3.21 g of the title compound as a pale-pink crystal. Thus, 40.3 g of the title compound was obtained in total (yield: 85%).

Workup

  1. temperaturewas cooled with ice
  2. temperatureunder cooling with ice for one hour
  3. customThe obtained reaction mixture
  4. stirringwas stirred
  5. temperatureunder cooling with ice for one hour
  6. extractionThe obtained mixture was extracted with chloroform
  7. washThe organic phase was washed with a saturated aqueous solution of common salt
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated in a vacuum
  10. concentrationIn the course of the concentration
  11. customto precipitate
  12. filtrationThis crystal was recovered by filtration

Sources & evidence

ORD record
ord-955a43bc1f604c958e0bc627d073874f
Source dataset
uspto-grants-1995_08
Patent number
US05444066

Reaction notes

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