Cyanamide → [4-Amino-2-[4-(2-dimethylaminoethoxy)-phenylamino]-thiazol-5-yl]-(3-methoxy-phenyl)-methanone

HRID 2415293Notes

Reaction equation

HRID 2415293 reaction equation
[N:1]([C:4]1[CH:15]=[CH:14][C:7]([O:8][CH2:9][CH2:10][N:11]([CH3:13])[CH3:12])=[CH:6][CH:5]=1)=[C:2]=[S:3].[N:16]#[C:17][NH2:18].CC(C)([O-])C.[K+].Br[CH2:26][C:27]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=1)=[O:28]>C(#N)C.C(O)(C)(C)C.CCOCC.Cl.CCOCC>[NH2:16][C:17]1[N:18]=[C:2]([NH:1][C:4]2[CH:15]=[CH:14][C:7]([O:8][CH2:9][CH2:10][N:11]([CH3:12])[CH3:13])=[CH:6][CH:5]=2)[S:3][C:26]=1[C:27]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=1)=[O:28]

Participants

9

Reactant 4

HCID 9864CyanamideHCID 101294Bromomethyl 3-methoxyphenyl ketoneHCID 226409714-[2-(Dimethylamino)ethoxy]phenyl isothiocyanateHCID 23665647Potassium tert-butoxide

Product 1

HCID 10001723[4-Amino-2-[4-(2-dimethylaminoethoxy)-phenylamino]-thiazol-5-yl]-(3-methoxy-phenyl)-methanoneYield 42%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolventHCID 10953452Ether hydrochlorideSolvent

Procedure

To a stirred mixture of [2-(4-isothiocyanato-phenoxy)-ethyl]-dimethylamine (0.6 g, 2.7 mmol) (from Step A) and cyanamide (0.123 g, 2.95 mmol) in acetonitrile (10 mL) and tert-butanol (10 mL), a solution of potassium tert-butoxide (2.7 mL, 1.0 M in tert-BuOH) was added. After 30 minutes at room temperature, 2-bromo-3′-methoxyacetophenone was added. The reaction mixture was stirred at room temperature for 1 hour and then refluxed for 1 hour. The chilled reaction mixture was diluted with ether and excess anhydrous hydrochloric acid/ether solution was added. The solids were filtered, washed with ether and then dissolved in dichloromethane/aqueous sodium bicarbonate. The dried (Na2SO4) organic solution was diluted with toluene (25 mL), concentrated, and refluxed to remove dichloromethane, The cooled mixture was diluted with hexane and filtered to give 0.47 g (42%) of [4-amino-2-[4-(2-dimethylaminoethoxy)-phenylamino]-thiazol-5-yl]-(3-methoxy-phenyl)-methanone as a yellow solid, mp 130° C. (dec). Mass spectrum (ES) MH+=413.

Workup

  1. temperaturerefluxed for 1 hour
  2. customThe chilled reaction mixture
  3. additionwas added
  4. filtrationThe solids were filtered
  5. washwashed with ether
  6. dissolutiondissolved in dichloromethane/aqueous sodium bicarbonate
  7. dry with materialThe dried (Na2SO4) organic solution
  8. additionwas diluted with toluene (25 mL)
  9. concentrationconcentrated
  10. temperaturerefluxed
  11. customto remove dichloromethane
  12. additionThe cooled mixture was diluted with hexane
  13. filtrationfiltered

Sources & evidence

ORD record
ord-aa9db080915744bb9a8fdb830efbbac9
Source dataset
uspto-grants-2004_11
Patent number
US06818663B2

Reaction notes

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