Reaktion #10909

Reaktionsgleichung

2-bromo-1-(3-methylsulfanyl-phenyl)ethanone

1-(4-isothiocyanatophenyl)-4-methylpiperazine

cyanamide

potassium tert-butoxide

→

[4-amino-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-5-thiazolyl](3-methylsulfanyl-phenyl)methanone

Ausbeute 50.0%

Lösungsmittel

ethyl acetate

acetonitrile

t-butanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITION0.49 g, 2.0 mmol) was added
2. 2
   Temperaturrefluxed for 15 minutes
3. 3
   Waschenwashed in turn with saturated aqueous sodium carbonate and brine
4. 4
   TrocknenThe dried (sodium sulfate) solution
5. 5
   Sonstigewas evaporated
6. 6
   Sonstigethe residue chromatographed on silica gel
7. 7
   WaschenElution of the desired product
8. 8
   Sonstigewith 9:1 dichloromethane/methanol and crystallization from ethyl acetate/hexane

Vorschrift

To a mixture of 1-(4-isothiocyanatophenyl)-4-methylpiperazine (of Example 1; 0.466 g, 2.0 mmol) and cyanamide (0.088 g, 2.1 mmol) in acetonitrile (3 mL) and t-butanol (5 ml), a solution of potassium tert-butoxide (2.0 mL, 1.0 M in tert-BuOH) was added. After 30 minutes at room temperature, 2-bromo-1-(3-methylsulfanyl-phenyl)ethanone (which can be prepared by the procedure of Rogers, N. H. et. al. EP 87953; 0.49 g, 2.0 mmol) was added. The reaction mixture was stirred at room temperature for 1 hour and then refluxed for 15 minutes. The cooled mixture was diluted with ethyl acetate and washed in turn with saturated aqueous sodium carbonate and brine. The dried (sodium sulfate) solution was evaporated and the residue chromatographed on silica gel. Elution of the desired product with 9:1 dichloromethane/methanol and crystallization from ethyl acetate/hexane provided 0.439 g (50% yield) of [4-amino-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-5-thiazolyl](3-methylsulfanyl-phenyl)methanone. Mass spectrum (ES) MH+=440.

Quelle