N-(4-chlorophenyl)propanethioamide → [[2-(1,5-dihydro-3-methoxy-1-methyl-5-oxo4H-1,2,4-triazol-4-yl)phenyl]methyl]N-(4-chlorophenyl)propanimidothioate

HRID 1106694Notes

Reaction equation

HRID 1106694 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[C:13]([O:14][CH3:15])=[N:12][N:11]([CH3:16])[C:10]1=[O:17].[Cl:18][C:19]1[CH:29]=[CH:28][C:22]([NH:23][C:24](=[S:27])[CH2:25][CH3:26])=[CH:21][CH:20]=1.CC(C)([O-])C.[K+]>C1COCC1.C(OCC)(=O)C>[CH3:15][O:14][C:13]1[N:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[CH2:2][S:27][C:24](=[N:23][C:22]2[CH:21]=[CH:20][C:19]([Cl:18])=[CH:29][CH:28]=2)[CH2:25][CH3:26])[C:10](=[O:17])[N:11]([CH3:16])[N:12]=1

Participants

6

Reactant 3

HCID 4154740N-(4-chlorophenyl)propanethioamideHCID 110338324-[2-(Bromomethyl)phenyl]-2,4-dihydro-5-methoxy-2-methyl-3H-1,2,4-triazol-3-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 15457013[[2-(1,5-dihydro-3-methoxy-1-methyl-5-oxo4H-1,2,4-triazol-4-yl)phenyl]methyl]N-(4-chlorophenyl)propanimidothioateYield 95%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.50 g of the title compound of Step D in 2 mL of THF was added 0.37 g of 4'-chlorothiopropionanilide and then 0.23 g of potassium tert-butoxide. (An exotherm occurred during this addition). The reaction was allowed to stir at room temperature overnight and then was heated briefly to reflux and allowed to cool. The reaction mixture was diluted with ethyl acetate and washed successively with water and then with saturated aqueous NaCl. The organic phase was dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (50-60% ethyl acetate/hexanes) to afford 0.48 g of the title compound of Step E (about 95% pure), a compound of the invention. 1H NMR (CDCl3): δ 7.58 (m,1H), 7.37 (m,2H), 7.23 (m,3H), 6.60 (d,2H), 4.23 (s,2H), 3.86 (s,3H), 3.41 (s,3H).

Workup

  1. addition(An exotherm occurred during this addition)
  2. temperaturewas heated briefly
  3. temperatureto reflux
  4. temperatureto cool
  5. washwashed successively with water
  6. dry with materialThe organic phase was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography (50-60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1dcc23cfbead4e749c25dc3754f588e5
Source dataset
uspto-grants-2000_05
Patent number
US06057352

Reaction notes

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