1,3-Dichloro-2-isothiocyanatobenzene → 2-[4-cyano-2-(2,6-dichloro-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl ester

HRID 562423Notes

Reaction equation

HRID 562423 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]=[C:10]=S.[CH2:12]([O:14][C:15](=[O:32])[C:16]([C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[C:23]([NH:28][CH3:29])[C:22]=1[C:30]#[N:31])([CH3:20])[C:17](=[O:19])[CH3:18])[CH3:13]>C1COCC1>[CH2:12]([O:14][C:15](=[O:32])[C:16]([C:21]1[CH:26]=[CH:25][C:24]2[N:27]=[C:10]([NH:9][C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=3[Cl:8])[N:28]([CH3:29])[C:23]=2[C:22]=1[C:30]#[N:31])([CH3:20])[C:17](=[O:19])[CH3:18])[CH3:13]

Participants

4

Reactant 2

HCID 1232391,3-Dichloro-2-isothiocyanatobenzeneHCID 110661612-(4-Amino-2-cyano-3-methylamino-phenyl)-2-methyl-3-oxo-butyric acid ethyl ester

Product 1

HCID 120354962-[4-cyano-2-(2,6-dichloro-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl esterYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,6-Dichlorophenyl isothiocyanate (3.46 g, 17.0 mmol), THF (100 mL), and 2-(4-amino-2-cyano-3-methylamino-phenyl)-2-methyl-3-oxo-butyric acid ethyl ester (4.91 g, 17.0 mmol), were added to a 250 mL round bottom flask equipped with a magnetic stir bar and the reaction was stirred at room temperature. After 2 hours, mercuric oxide (4.04 g, 18.7 mmol) was added and the reaction stirred for an additional 14 h. The resultant brown slurry was filtered through celite and washed with THF. The filtrate was concentrated and the residue triturated with diethyl ether to provide 2-[4-cyano-2-(2,6-dichloro-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl ester (4.2 g, 54%) as a gray solid, which was used without further purification.

Workup

  1. customequipped with a magnetic stir bar
  2. stirringthe reaction stirred for an additional 14 h
  3. filtrationThe resultant brown slurry was filtered through celite
  4. washwashed with THF
  5. concentrationThe filtrate was concentrated
  6. customthe residue triturated with diethyl ether

Sources & evidence

ORD record
ord-be2425312133486397c2b8d9b92db14f
Source dataset
uspto-grants-2011_11
Patent number
US08067395B2

Reaction notes

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