Cesium carbonate → HCID 68261003, compound

HRID 525183Notes

Reaction equation

HRID 525183 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]([F:25])[C:3]=1[F:26].CC1(C)C(C)(C)OB([C:35]2[CH:36]=[CH:37][C:38]3[O:42][CH:41]=[CH:40][C:39]=3[CH:43]=2)O1.C(=O)([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:42]1[C:38]2[CH:37]=[CH:36][C:35]([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[CH2:23][CH2:22]6)=[O:20])[CH2:15]5)=[N:11][NH:10][C:9]4=[O:24])=[C:4]([F:25])[C:3]=3[F:26])=[CH:43][C:39]=2[CH:40]=[CH:41]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27951905-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuranHCID 71087482HCID 71087482, compound

Product 1

HCID 68261003HCID 68261003, compoundYield 68.1%

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

To a microwave vial were added 4-(4-bromo-2,3-difluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (50 mg, 0.117 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (42.8 mg, 0.176 mmol), cesium carbonate (114 mg, 0.351 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (6.0 mg, 0.00735 mmol). The mixture was purged with nitrogen, followed by the addition of 1,4-dioxane (1 mL) and water (0.5 mL). The resulting suspension was heated overnight at 100° C., at which point 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+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 Na2SO4 and concentrated in vacuo to afford the title product as a white solid (37 mg, 68%). MS(ES)+ m/e 465.1 M+H]+.

Workup

  1. customThe mixture was purged with nitrogen
  2. additionfollowed by the addition of 1,4-dioxane (1 mL) and water (0.5 mL)
  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+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 Na2SO4
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ee06d58594384aa28378b89640364d47
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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