Water → 1H-Imidazole-2-methanol, 5-((3,5-dichlorophenyl)thio)-4-(1-methylethyl)-1-(2-(2-pyridinyl)ethyl)-, carbamate (ester)

HRID 1857748Notes

Reaction equation

HRID 1857748 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:9][C:10]2[N:14]([CH2:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[C:13]([CH2:23][OH:24])=[N:12][C:11]=2[CH:25]([CH3:27])[CH3:26])[CH:5]=[C:6]([Cl:8])[CH:7]=1.ClC(Cl)(Cl)[C:30]([N:32]=C=O)=[O:31].C(N(CC)CC)C.O>O1CCCC1.CO>[C:30]([O:24][CH2:23][C:13]1[N:14]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[C:10]([S:9][C:4]2[CH:3]=[C:2]([Cl:1])[CH:7]=[C:6]([Cl:8])[CH:5]=2)=[C:11]([CH:25]([CH3:27])[CH3:26])[N:12]=1)(=[O:31])[NH2:32]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 76400Trichloroacetyl isocyanateHCID 4740461H-Imidazole-2-methanol, 5-((3,5-dichlorophenyl)thio)-4-(1-methylethyl)-1-(2-(2-pyridinyl)ethyl)-

Product 1

HCID 4740471H-Imidazole-2-methanol, 5-((3,5-dichlorophenyl)thio)-4-(1-methylethyl)-1-(2-(2-pyridinyl)ethyl)-, carbamate (ester)Yield 91%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

In 20 ml of tetrahydrofuran was dissolved 521 mg of 5-(3,5-dichlorophenylthio)-4-isopropyl-2-hydroxymethyl-1-(2-(2-pyridyl)ethyl)-1H-imidazole (112a), and the mixture was cooled to -40° C. Under stirring, 221 μl of trichloroacetylisocyanate was added, the mixture was allowed to stand to reach room temperature, and stirred for 30 minutes. Added was 500 μl of triethylamine, 5 ml of water and 5 ml of methanol, and the mixture was stirred at 70° C. for 1 hour. After completion of the reaction, the soluvent was distilled off under reduced pressure, an aqueous sodium hydrogen carbonate solution was added, and extracted with ethyl acetate. The extract was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1) to give 520 mg of Compound I-129 (yield 91%).

Workup

  1. customto reach room temperature
  2. stirringstirred for 30 minutes
  3. additionAdded
  4. stirringthe mixture was stirred at 70° C. for 1 hour
  5. customAfter completion of the reaction
  6. distillationthe soluvent was distilled off under reduced pressure
  7. additionan aqueous sodium hydrogen carbonate solution was added
  8. extractionextracted with ethyl acetate
  9. dry with materialThe extract was dried over sodium sulfate
  10. distillationthe solvent was distilled off under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1)

Sources & evidence

ORD record
ord-ffc371eea1514c73bc2a8a43e00219d4
Source dataset
uspto-grants-2000_11
Patent number
US06147097

Reaction notes

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