Dimethylformamide → HCID 54529357, compound

HRID 1735895Notes

Reaction equation

HRID 1735895 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][C@H:6]([N:13]1[C:17]([CH2:18]O)=[CH:16][NH:15][C:14]1=[S:20])[CH2:7]2.CN(C=O)C.S(Cl)(Cl)=O.[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1>C1COCC1>[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][C@H:6]([N:13]1[C:17]([CH2:18][N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)=[CH:16][NH:15][C:14]1=[S:20])[CH2:7]2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 31268PyrrolidineHCID 15290000HCID 15290000, compound

Product 1

HCID 54529357HCID 54529357, compoundYield 61.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-1-(5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)-5-hydroxymethyl-1,3-dihydroimidazole-2-thione (140 mg, 0.47 mmol), prepared as in Example 18, in 20 mL of THF and I drop of DMF was cooled to between 0° and 5° C. and thionyl chloride (13.7 M, 109 μL, 1.49 mmol) was added drop-wise under a nitrogen atmosphere. The mixture was stirred at room temperature for 0.5 hours, under reflux for 0.5 hours and again at room temperature for 0.5 hours. The mixture then was cooled to between 0° and 5° C. and pyrrolidine (12.0 M, 818 μL, 9.8 mmol) was added drop-wise. The mixture was stirred under reflux for 1.5 hours. The solvents were removed by evaporation and the residue was diluted with water. Ethyl acetate was added to the dilution and the mixture was adjusted to pH 7. The ethyl acetate layer was dried and concentrated by evaporation. Purification of the residue by column chromatography gave (S)-1-(5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)-1,3-dihydro-5-(pyrrolidin-1-ylmethyl)-imidazole-2-thione (100 mg, 0.29 mmol). [α]D =-10.96° (C=1.3, DMSO).

Workup

  1. temperaturewas cooled to between 0° and 5° C.
  2. temperatureunder reflux for 0.5 hours and again at room temperature for 0.5 hours
  3. temperatureThe mixture then was cooled to between 0° and 5° C.
  4. stirringThe mixture was stirred
  5. temperatureunder reflux for 1.5 hours
  6. customThe solvents were removed by evaporation
  7. additionthe residue was diluted with water
  8. additionEthyl acetate was added to the dilution
  9. dry with materialThe ethyl acetate layer was dried
  10. concentrationconcentrated by evaporation
  11. customPurification of the residue by column chromatography

Sources & evidence

ORD record
ord-5ab0c4a1f598481fb7c50a5999063d40
Source dataset
uspto-grants-1996_07
Patent number
US05538988

Reaction notes

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