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

HRID 2213917Notes

Reaction equation

HRID 2213917 reaction equation
[N:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)=[C:2]=[S:3].[N:17]#[C:18][NH2:19].CC(C)([O-])C.[K+].Br[CH2:27][C:28]([C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([S:36][CH3:37])[CH:31]=1)=[O:29]>C(#N)C.C(O)(C)(C)C.C(OCC)(=O)C>[NH2:17][C:18]1[N:19]=[C:2]([NH:1][C:4]2[CH:5]=[CH:6][C:7]([N:10]3[CH2:11][CH2:12][N:13]([CH3:16])[CH2:14][CH2:15]3)=[CH:8][CH:9]=2)[S:3][C:27]=1[C:28]([C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([S:36][CH3:37])[CH:31]=1)=[O:29]

Participants

8

Reactant 4

HCID 9864CyanamideHCID 137183971-(4-Isothiocyanatophenyl)-4-methylpiperazineHCID 219589582-Bromo-1-(3-(methylthio)phenyl)ethanoneHCID 23665647Potassium tert-butoxide

Product 1

HCID 21958922[4-Amino-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-5-thiazolyl](3-methylsulfanyl-phenyl)methanoneYield 50%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

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.

Workup

  1. addition0.49 g, 2.0 mmol) was added
  2. temperaturerefluxed for 15 minutes
  3. washwashed in turn with saturated aqueous sodium carbonate and brine
  4. dry with materialThe dried (sodium sulfate) solution
  5. customwas evaporated
  6. customthe residue chromatographed on silica gel
  7. washElution of the desired product
  8. customwith 9:1 dichloromethane/methanol and crystallization from ethyl acetate/hexane

Sources & evidence

ORD record
ord-1e0f1399e34143f3aa675cae0cee1933
Source dataset
uspto-grants-2006_09
Patent number
US07105670B2

Reaction notes

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