Chloroacetyl isocyanate → 1H-Imidazole-2-methanol, 5-((3,5-dichlorophenyl)thio)-4-(1-methylethyl)-1-(3-quinolinylmethyl)-, carbamate (ester)

HRID 1416054Notes

Reaction equation

HRID 1416054 reaction equation
[OH:1][CH2:2][C:3]1[N:4]([CH2:20][C:21]2[CH:22]=[N:23][C:24]3[C:29]([CH:30]=2)=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:5]([S:11][C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[C:14]([Cl:19])[CH:13]=2)=[C:6]([CH:8]([CH3:10])[CH3:9])[N:7]=1.ClC[C:33]([N:35]=C=O)=[O:34].C(=O)(O)[O-].[Na+]>O1CCCC1.CO.[Zn]>[C:33]([O:1][CH2:2][C:3]1[N:4]([CH2:20][C:21]2[CH:22]=[N:23][C:24]3[C:29]([CH:30]=2)=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:5]([S:11][C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[C:14]([Cl:19])[CH:13]=2)=[C:6]([CH:8]([CH3:10])[CH3:9])[N:7]=1)(=[O:34])[NH2:35]

Participants

7

Reactant 3

HCID 78209Chloroacetyl isocyanateHCID 4740441H-Imidazole-2-methanol, 5-((3,5-dichlorophenyl)thio)-4-(1-methylethyl)-1-(3-quinolinylmethyl)-HCID 516892Sodium Bicarbonate2×

Product 1

HCID 4740451H-Imidazole-2-methanol, 5-((3,5-dichlorophenyl)thio)-4-(1-methylethyl)-1-(3-quinolinylmethyl)-, carbamate (ester)Yield 78%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

In 5 ml of tetrahydrofuran was dissolved 223 mg (0.50 mmol)of 2-hydroxymethyl-5-(3,5-dichlorophenylthio)-4-isopropyl-1-(quinolin-3-ylmethyl)-1H-imidazole (109), followed by dropwise addition of 72 mg (0.60 mmol)of chloroacetylisocyanate with stirring at 0° C., and the mixture was stirred at room temperature for 30 minutes. After the reaction completion, the mixture was worked up. To the reaction mixture was added a saturated aqueous sodium bicarbonate solution, extracted with methylene chloride, the extract was washed with water and dried. The-solvent was distilled off under reduced pressure, and 2-chloroacetyl-carbamoyloxymethyl-5-(3,5-dichlorophenylthio)-4-isopropyl-1-(quinolin-3-ylmethyl)-1H-imidazole (110)suited to the next step of the reaction was obtained. mp 167-170° C. The crystals were dissolved in 20 ml of aqueous methanol, 40 mg of Zn powder was added, and the mixture was stirred at room temperature for 5 hours. After the reaction completion, the mixture was worked up. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution, and the insoluble material was removed by filtration under reduced pressure through Celite. The filtrate was concentrated, extracted with methylene chloride, the extract was washed with water and dried, and the solvent was distilled off. The residual crystals were washed with ethyl acetate and ether to give 195 mg of Compound I-128 (yield 78%). mp 214-216° C.

Workup

  1. stirringthe mixture was stirred at room temperature for 30 minutes
  2. extractionextracted with methylene chloride
  3. washthe extract was washed with water
  4. customdried
  5. distillationThe-solvent was distilled off under reduced pressure, and 2-chloroacetyl-carbamoyloxymethyl-5-(3,5-dichlorophenylthio)-4-isopropyl-1-(quinolin-3-ylmethyl)-1H-imidazole (110)suited to the next step of the reaction
  6. customwas obtained
  7. stirringthe mixture was stirred at room temperature for 5 hours
  8. customthe insoluble material was removed by filtration under reduced pressure through Celite
  9. concentrationThe filtrate was concentrated
  10. extractionextracted with methylene chloride
  11. washthe extract was washed with water
  12. customdried
  13. distillationthe solvent was distilled off
  14. washThe residual crystals were washed with ethyl acetate and ether

Sources & evidence

ORD record
ord-ebd997c20c4047e99c009324b4d8db96
Source dataset
uspto-grants-1999_06
Patent number
US05910506

Reaction notes

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