Reaction #10909

Reaction equation

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

Yield 50.0%

Solvents

ethyl acetate

acetonitrile

t-butanol

Conditions

Workup

1. 1
   workup.ADDITION0.49 g, 2.0 mmol) was added
2. 2
   Temperaturerefluxed for 15 minutes
3. 3
   Washwashed in turn with saturated aqueous sodium carbonate and brine
4. 4
   DryingThe dried (sodium sulfate) solution
5. 5
   Otherwas evaporated
6. 6
   Otherthe residue chromatographed on silica gel
7. 7
   WashElution of the desired product
8. 8
   Otherwith 9:1 dichloromethane/methanol and crystallization from ethyl acetate/hexane

Procedure

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.

Source