Cesium carbonate → 4-[4-(1-benzofuran-5-yl)-2-(trifluoromethyl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 2405358Notes

Reaction equation

HRID 2405358 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][C@@H:14]3[CH2:18][CH2:17][N:16]([C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[CH2:15]3)=[N:11][NH:10][C:9]2=[O:24])=[C:4]([C:25]([F:28])([F:27])[F:26])[CH:3]=1.[C:29](=[O:32])([O-])[O-].[Cs+].[Cs+]>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>[O:32]1[C:29]2[CH:5]=[CH:6][C:7]([C:2]3[CH:7]=[CH:6][C:5]([N:8]4[C:12]([CH2:13][C@@H:14]5[CH2:18][CH2:17][N:16]([C:19]([CH:21]6[CH2:22][CH2:23]6)=[O:20])[CH2:15]5)=[N:11][NH:10][C:9]4=[O:24])=[C:4]([C:25]([F:28])([F:26])[F:27])[CH:3]=3)=[CH:2][C:3]=2[CH:4]=[CH:25]1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 673538084-[4-bromo-2-(trifluoromethyl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one2×

Product 1

HCID 682610004-[4-(1-benzofuran-5-yl)-2-(trifluoromethyl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 83.9%

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

To a microwave vial were added 4-[4-bromo-2-(trifluoromethyl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (55 mg, 0.072 mmol), 4-[4-bromo-2-(trifluoromethyl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (55 mg, 0.072 mmol), cesium carbonate (82 mg, 0.251 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (6.0 mg, 0.00735 mmol) and the mixture was purged with nitrogen. 1,4-Dioxane (1 mL) and water (0.5 mL) were added to the mixture which was heated overnight at 100° C. Analysis by LCMS indicated desired product formation and consumption of starting material. The mixture was filtered through a syringe filter and purified by reverse phase HPLC (10-90% acetonitrile/water with 0.1% TFA). The desired fractions were collected and added to a reparatory funnel containing ethyl acetate. The aqueous phase was adjusted to pH˜6 with 1N aq HCl. The aqueous phase was extracted with ethyl acetate (3×), and the combined organics were washed with brine, dried over sodium sulfate, and concentrated in vacuo to afford the title product as a tan solid (15 mg, 41%). MS(ES)+ m/e 497.2 [M+H]+.

Workup

  1. customthe mixture was purged with nitrogen
  2. addition1,4-Dioxane (1 mL) and water (0.5 mL) were added to the mixture which
  3. customdesired product formation and consumption of starting material
  4. filtrationThe mixture was filtered through a syringe
  5. filtrationfilter
  6. custompurified by reverse phase HPLC (10-90% acetonitrile/water with 0.1% TFA)
  7. customThe desired fractions were collected
  8. additionadded to a reparatory funnel
  9. additioncontaining ethyl acetate
  10. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  11. washthe combined organics were washed with brine
  12. dry with materialdried over sodium sulfate
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ca46802ff66a4430acfe817fd14dd455
Source dataset
uspto-grants-2014_08
Patent number
US08802864B2

Reaction notes

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