Potassium Acetate → HCID 71263607, compound

HRID 1424826Notes

Reaction equation

HRID 1424826 reaction equation
Br[C:2]1[C:7]([F:8])=[CH:6][C:5]([N:9]([C:14]2[C:33]([CH:34]3[CH2:36][CH2:35]3)=[CH:32][C:17]3[C:18]([C:28]([NH:30][CH3:31])=[O:29])=[C:19]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[O:20][C:16]=3[CH:15]=2)[S:10]([CH3:13])(=[O:12])=[O:11])=[CH:4][C:3]=1[F:37].C([O-])(=O)C.[K+].[B:43]1(B2OC(C)(C)C(C)(C)O2)[O:47]C(C)(C)C(C)(C)[O:44]1>O1CCOCC1.CCOC(C)=O.O.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].C(Cl)Cl>[CH:34]1([C:33]2[C:14]([N:9]([C:5]3[CH:4]=[C:3]([F:37])[C:2]([B:43]([OH:47])[OH:44])=[C:7]([F:8])[CH:6]=3)[S:10]([CH3:13])(=[O:11])=[O:12])=[CH:15][C:16]3[O:20][C:19]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)=[C:18]([C:28](=[O:29])[NH:30][CH3:31])[C:17]=3[CH:32]=2)[CH2:36][CH2:35]1

Participants

8

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 131732285HCID 131732285, compound

Product 1

HCID 71263607HCID 71263607, compoundYield 19.4%

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 6-(N-(4-bromo-3,5-difluorophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (0.093 g, 0.157 mmol), potassium acetate (0.062 g, 0.627 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.013 g, 0.016 mmol), bis(pinacolato)diboron (0.080 g, 0.31 mmol) in 1,4-Dioxane (1.6 ml) was degassed, purged with nitrogen and heated at 90° C. for 4 h. The reaction mixture was diluted with EtOAc and water, filtered through celite, and evaporated. The brown residue was dissolved in 5 mL THF, and 2.5 mL 1M HCl. NaIO4 (0.27 g, 1.25 mmol) was added and the suspension was stirred for 2.5 h and diluted with EtOAc and water. The organic layer was washed with water, brine, dried (Na2SO4), filtered, evaporated and purified by reverse phase chromatography (5-100% CH3CN/H2O (0.1% formic acid)) to afford the title compound (0.017 g, 19%) as a white solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.91-7.98 (m, 2H), 7.79 (s, 1H), 7.34 (s, 1H), 7.20-7.29 (m, 2H), 6.82-6.92 (m, 2H), 3.38 (s, 3H), 2.95 (s, 3H), 2.01-2.11 (m, 1H), 0.70-1.07 (m, 3H), 0.54 (br. s., 1H). LCMS (m/z, ES+)=559.3 (M+H+).

Workup

  1. custompurged with nitrogen
  2. additionThe reaction mixture was diluted with EtOAc and water
  3. filtrationfiltered through celite
  4. customevaporated
  5. dissolutionThe brown residue was dissolved in 5 mL THF
  6. washThe organic layer was washed with water, brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated
  10. custompurified by reverse phase chromatography (5-100% CH3CN/H2O (0.1% formic acid))

Sources & evidence

ORD record
ord-0d729e179aae4e95bb8c58ab823e4acf
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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