Cesium carbonate → HCID 71087321, compound

HRID 2405417Notes

Reaction equation

HRID 2405417 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:13]([CH2:14][C@@H:15]3[CH2:19][CH2:18][N:17]([C:20]([CH:22]4[CH2:24][CH2:23]4)=[O:21])[CH2:16]3)=[N:12][NH:11][C:10]2=[O:25])=[C:4]([Cl:26])[CH:3]=1.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]=[C:6]([F:8])[C:5]([N:9]4[C:13]([CH2:14][C@@H:15]5[CH2:19][CH2:18][N:17]([C:20]([CH:22]6[CH2:24][CH2:23]6)=[O:21])[CH2:16]5)=[N:12][NH:11][C:10]4=[O:25])=[C:4]([Cl:26])[CH:3]=3)=[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 71087621HCID 71087621, compound

Product 1

HCID 71087321HCID 71087321, compound

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

To a microwave vial were added 4-(4-bromo-2-chloro-6-fluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (0.027 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (0.04 mmol), cesium carbonate (0.08 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (0.0012 mmol). The mixture was purged with nitrogen and suspended in 1,4-dioxane (0.3 mL) and water (0.15 mL). The mixture was heated for 15 h 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+0.1% TFA). The desired fractions were collected and added to a separatory 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 to afford the title product as an off-white solid and nearly equal mixture of atropisomeric diastereomers (7.0 mg, 54%). MS(ES)+ m/e 481.0 [M+H]+.

Workup

  1. customThe mixture was purged with nitrogen
  2. customdesired product formation and consumption of starting material
  3. filtrationThe mixture was filtered through a syringe
  4. filtrationfilter
  5. custompurified by reverse phase HPLC (10-90% acetonitrile/water+0.1% TFA)
  6. customThe desired fractions were collected
  7. additionadded to a separatory funnel
  8. additioncontaining ethyl acetate
  9. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  10. washthe combined organics were washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. customto afford

Sources & evidence

ORD record
ord-8d78cce5761046e7acc1f8193b0a9b9a
Source dataset
uspto-grants-2014_08
Patent number
US08802864B2

Reaction notes

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