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

HRID 525256Notes

Reaction equation

HRID 525256 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[NH:11][N:10]=[C:9]2[CH2:14][C@@H:15]2[CH2:19][CH2:18][N:17]([C:20]([NH:22][CH2:23][CH3:24])=[O:21])[CH2:16]2)=[C:4]([F:25])[CH:3]=1.CC1(C)C(C)(C)OB([C:34]2[CH:43]=[C:42]3[C:37]([CH:38]=[CH:39][CH:40]=[N:41]3)=[CH:36][CH:35]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[CH2:23]([NH:22][C:20]([N:17]1[CH2:18][CH2:19][C@@H:15]([CH2:14][C:9]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([C:34]4[CH:43]=[C:42]5[C:37]([CH:38]=[CH:39][CH:40]=[N:41]5)=[CH:36][CH:35]=4)=[CH:3][C:4]=3[F:25])[C:12](=[O:13])[NH:11][N:10]=2)[CH2:16]1)=[O:21])[CH3:24]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 592961167-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)QuinolineHCID 67376184(3S)-3-{[4-(4-bromo-2-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-N-ethyl-1-pyrrolidinecarboxamide

Product 1

HCID 67375868(3S)-N-ethyl-3-({4-[2-fluoro-4-(7-quinolinyl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)-1-pyrrolidinecarboxamide

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of (3S)-3-{[4-(4-bromo-2-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-N-ethyl-1-pyrrolidinecarboxamide (0.179 mmol) in dioxane (2 mL) was treated with 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (0.180 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (15 mg), and 2M aq potassium carbonate (1 mL). The reaction mixture was purged with nitrogen, sealed, and stirred at 110° C. for 1 h. The solution was cooled to room temperature and the dioxane layer separated from the aqueous layer. The dioxane layer was removed via pipette and was passed through a plug of celite and sodium sulfate. The plug was washed with dioxane (2 mL). All dioxane filtrates were combined and concentrated in vacuo. Reverse phase HPLC (10-70% acetonitrile/water+0.1% NH4OH) was utilized in purifying the title compound (29 mg, 35%). MS(ES)+ m/e 461.2 [M+H]+.

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. customsealed
  3. temperatureThe solution was cooled to room temperature
  4. customthe dioxane layer separated from the aqueous layer
  5. customThe dioxane layer was removed via pipette
  6. washThe plug was washed with dioxane (2 mL)
  7. concentrationconcentrated in vacuo
  8. customin purifying the title compound (29 mg, 35%)

Sources & evidence

ORD record
ord-e994dd96e3da4c6eae362a754c06670d
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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