Hydrochloric Acid → (3S)-3-({4-[2-fluoro-4-(7-quinolinyl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)-N,N-dimethyl-1-pyrrolidinecarboxamide

HRID 525253Notes

Reaction equation

HRID 525253 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[CH:10][CH:9]=2)[CH:5]=[CH:4][C:3]=1[N:18]1[C:22](=[O:23])[NH:21][N:20]=[C:19]1[CH2:24][C@@H:25]1[CH2:29][CH2:28][N:27]([C:30]([O:32]C(C)(C)C)=O)[CH2:26]1.Cl.[CH:38]([N:41](CC)[CH:42](C)C)(C)C.CNN(NC)C(Cl)=O.[NH4+].[Cl-]>O1CCOCC1.ClCCl>[F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[CH:10][CH:9]=2)[CH:5]=[CH:4][C:3]=1[N:18]1[C:22](=[O:23])[NH:21][N:20]=[C:19]1[CH2:24][C@@H:25]1[CH2:29][CH2:28][N:27]([C:30]([N:41]([CH3:42])[CH3:38])=[O:32])[CH2:26]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 673549061,1-dimethylethyl (3S)-3-({4-[2-fluoro-4-(7-quinolinyl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)-1-pyrrolidinecarboxylateHCID 86674832N,N-dimethylaminocarbamoyl chloride

Product 1

HCID 67380101(3S)-3-({4-[2-fluoro-4-(7-quinolinyl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)-N,N-dimethyl-1-pyrrolidinecarboxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 312751,4-DioxaneSolvent

Procedure

Into a 8 mL screwcap vial was placed 1,1-dimethylethyl (3S)-3-({4-[2-fluoro-4-(7-quinolinyl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}-methyl)-1-pyrrolidinecarboxylate (0.161 mmol). Added to the vial was 4N HCl in dioxane (1 mL). The reaction mixture was capped and stirred at room temperature for 2 h. The solution was concentrated in vacuo. Added to the vial were dichloromethane (1 mL) and N,N-diisopropylethylamine (0.573 mmol). In a separate vial, N,N-dimethylaminocarbamoyl chloride (0.161 mmol) was dissolved in 1 mL dichloromethane and added to the starting material dropwise via pipette. The vial was capped and the reaction was stirred at room temperature for 2 h. An extra 2 mL dichloromethane was added to the vial, followed by the addition of saturated aq NH4Cl (2 mL). The vial was capped and lightly agitated for 1 min. The organic layer was separated, filtered through a plug of sodium sulfate, and concentrated in vacuo. Reverse phase HPLC (10-65% acetonitrile/water+0.1% NH4OH) was utilized in purifying the title compound (44 mg, 59%). MS(ES)+ m/e 461.2 [M+H]+.

Workup

  1. additionAdded to the vial
  2. customThe reaction mixture was capped
  3. concentrationThe solution was concentrated in vacuo
  4. additionAdded to the
  5. additionadded to the starting material dropwise via pipette
  6. customThe vial was capped
  7. stirringthe reaction was stirred at room temperature for 2 h
  8. customThe vial was capped
  9. stirringlightly agitated for 1 min
  10. customThe organic layer was separated
  11. filtrationfiltered through a plug of sodium sulfate
  12. concentrationconcentrated in vacuo
  13. customin purifying the title compound (44 mg, 59%)

Sources & evidence

ORD record
ord-ca44d6b7f89c451ba463d85a60a4aeeb
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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