Cyanamide → HCID 21958922, compound

HRID 10813Notes

Reaction equation

HRID 10813 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-(methylsulfanyl)phenyl]ethan-1-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 21958922HCID 21958922, compoundYield 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-eeb6facdc8e0446389e7e7456b4ead4b
Source dataset
uspto-grants-2006_08
Patent number
US07094896B2

Reaction notes

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