Potassium Acetate → HCID 71263605, compound

HRID 1424822Notes

Reaction equation

HRID 1424822 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]([C:13]2[C:32]([CH:33]3[CH2:35][CH2:34]3)=[CH:31][C:16]3[C:17]([C:27]([NH:29][CH3:30])=[O:28])=[C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[O:19][C:15]=3[CH:14]=2)[S:9]([CH3:12])(=[O:11])=[O:10])=[CH:4][C:3]=1[C:36]([F:39])([F:38])[F:37].C([O-])(=O)C.[K+].[B:45]1(B2OC(C)(C)C(C)(C)O2)[O:49]C(C)(C)C(C)(C)[O:46]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:33]1([C:32]2[C:13]([N:8]([C:5]3[CH:6]=[CH:7][C:2]([B:45]([OH:49])[OH:46])=[C:3]([C:36]([F:37])([F:39])[F:38])[CH:4]=3)[S:9]([CH3:12])(=[O:10])=[O:11])=[CH:14][C:15]3[O:19][C:18]([C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)=[C:17]([C:27](=[O:28])[NH:29][CH3:30])[C:16]=3[CH:31]=2)[CH2:34][CH2:35]1

Participants

8

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 131732282HCID 131732282, compound

Product 1

HCID 71263605HCID 71263605, compoundYield 49%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
80 °C

Procedure

A solution of 6-(N-(4-bromo-3-(trifluoromethyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (0.20 g, 0.32 mmol), potassium acetate (0.13 g, 1.28 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.026 g, 0.032 mmol), bis(pinacolato)diboron (0.24 g, 0.96 mmol) in 1,4-dioxane (4 ml) was degassed, purged with nitrogen and heated at 80° C. for 4 h. The reaction mixture was diluted with EtOAc and water, filtered through celite, and evaporated. The brown residue was dissolved in 10 mL THF, and 5 mL 1M HCl. NaIO4 (0.64 g, 3.20 mmol) was added and the suspension was stirred for 3 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 (0.092 g, 49%) as a white solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.85-8.00 (m, 3H), 7.59-7.72 (m, 2H), 7.47 (d, 1H), 7.29-7.34 (m, 1H), 7.20-7.29 (m, 2H), 3.35 (s, 3H), 2.94 (s, 3H), 2.12 (tt, 1H), 0.28-1.10 (m, 4H). LCMS (m/z, ES+)=591.3 (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 10 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-e57ca180ba514a018f5df46e194f86c6
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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