Hydrochloric Acid → HCID 67377248, compound

HRID 2405444Notes

Reaction equation

HRID 2405444 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[C:12](=[O:13])[NH:11][N:10]=[C:9]1[CH2:14][C@@H:15]1[CH2:19][CH2:18][N:17]([C:20]([O:22]C(C)(C)C)=O)[CH2:16]1.Cl.[C:36](Cl)(=O)[CH:37](C)[CH3:38]>O1CCOCC1.ClCCl>[F:1][C:2]1[CH:3]=[C:4]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[C:9]([CH2:14][C@@H:15]2[CH2:19][CH2:18][N:17]([C:20](=[O:22])[CH:37]([CH3:38])[CH3:36])[CH2:16]2)=[N:10][NH:11][C:12]1=[O:13]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 62325Isobutyryl chlorideHCID 67376377HCID 67376377, compound

Product 1

HCID 67377248HCID 67377248, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

Into a 50 mL round bottom flask was placed 1,1-dimethylethyl (3S)-3-({4-[3-fluoro-4′-(methyloxy)-4-biphenylyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)-1-pyrrolidinecarboxylate (0.342 mmol). Added to the flask was 4N HCl in dioxane (2 mL). The flask was capped and the contents were stirred at room temperature for 1 h. The solution was concentrated in vacuo. Added to the flask in succession were dichloromethane (3 mL) and N,N-diisopropylethylamine (0.200 mL). The flask was cooled to 0° C. in an ice bath. In a separate vial, isobutryl chloride (0.348 mmol) was taken up with dichloromethane (2 mL) and was added to the cold solution dropwise via pipette. The reaction was stirred for 2 h while the ice bath was allowed to warm to room temperature. The reaction was then diluted with dichloromethane (20 mL) and washed with saturated aq NH4Cl. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo. Reverse phase HPLC (10-70% acetonitrile/water+0.1% NH4OH) was utilized in purifying the title compound (65 mg, 43%). MS(ES)+ m/e 439.1 [M+H]+.

Workup

  1. customInto a 50 mL round bottom flask was placed
  2. additionAdded to the flask
  3. customThe flask was capped
  4. concentrationThe solution was concentrated in vacuo
  5. additionAdded to the flask in succession
  6. temperatureThe flask was cooled to 0° C. in an ice bath
  7. additionwas added to the cold solution dropwise via pipette
  8. temperatureto warm to room temperature
  9. washwashed with saturated aq NH4Cl
  10. customThe organic layer was separated
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customin purifying the title compound (65 mg, 43%)

Sources & evidence

ORD record
ord-baa5acb8f21e4c1495fe1123e283bdea
Source dataset
uspto-grants-2014_08
Patent number
US08802864B2

Reaction notes

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