Hydrochloric Acid → HCID 71263611, compound

HRID 1424844Notes

Reaction equation

HRID 1424844 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[S:36]([CH3:39])(=[O:38])=[O:37].CC1(C)C(C)(C)[O:44][B:43](B2OC(C)(C)C(C)(C)O2)[O:42]1.C([O-])(=O)C.[K+].Cl.I([O-])(=O)(=O)=O.[Na+]>O1CCOCC1.CCOC(C)=O>[CH:33]1([C:32]2[C:13]([N:8]([C:5]3[CH:6]=[CH:7][C:2]([B:43]([OH:44])[OH:42])=[C:3]([S:36]([CH3:39])(=[O:38])=[O:37])[CH:4]=3)[S:9]([CH3:12])(=[O:11])=[O:10])=[CH:14][C:15]3[O:19][C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)=[C:17]([C:27](=[O:28])[NH:29][CH3:30])[C:16]=3[CH:31]=2)[CH2:35][CH2:34]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 23667635Sodium periodateHCID 131732296HCID 131732296, compound

Product 1

HCID 71263611HCID 71263611, compoundYield 6.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-(N-(4-bromo-3-(methylsulfonyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (200 mg, 0.315 mmol) in 1,4-Dioxane (2 mL) wad added 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (400 mg, 1.574 mmol), potassium acetate (154 mg, 1.574 mmol) and Pd(II)(dppf)Cl2 DCM complex (12.85 mg, 0.016 mmol). The mixture was stirred under nitrogen at 80° C. After 4 hours the mixture was cooled to RT and diluted with EtOAc (10 mL). The resulting solution was washed with water, saturated brine, and dried over sodium sulfate. After evaporation of the solvent, the crude residue was dissolved in 10 mL of THF and the resulting solution cooled in an ice water bath. The solution was treated with 1N aqueous HCl (1.574 mL, 1.574 mmol) followed by sodium periodate (135 mg, 0.629 mmol). The mixture was stirred at 0° C. for 20 minutes and then allowed to warm to RT. After 18 hours, the mixture was partitioned between water and EtOAc and the phases separated. The aqueous solution was extracted with EtOAc. The combined EtOAc solutions were washed with 5% aqueous sodium bisulfite, saturated brine, dried over sodium sulfate and concentrated to dryness at reduced pressure. The residue was subjected to HPLC purification (ACN: Water-0.1% Formic acid) to provide the pure product (12 mg, 6.4%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.97 (br. s., 2H), 7.87 (d, J=5.37 Hz, 2H), 7.56-7.64 (m, 2H), 7.49 (s, 1H), 7.15-7.24 (m, 2H), 6.15-6.37 (m, 1H), 5.77-5.92 (m, 1H), 3.30 (s, 3H), 3.13 (br. s., 3H), 3.00 (d, J=2.34 Hz, 3H), 1.91-2.10 (m, 1H), 1.18-1.34 (m, 1H), 0.95-1.10 (m, 1H), 0.83-0.93 (m, 1H), 0.69-0.83 (m, 1H), 0.44-0.61 (m, 1H). LCMS (m/z, ES+)=601 (M+H+).

Workup

  1. temperatureAfter 4 hours the mixture was cooled to RT
  2. washThe resulting solution was washed with water, saturated brine
  3. dry with materialdried over sodium sulfate
  4. customAfter evaporation of the solvent
  5. dissolutionthe crude residue was dissolved in 10 mL of THF
  6. temperaturethe resulting solution cooled in an ice water bath
  7. stirringThe mixture was stirred at 0° C. for 20 minutes
  8. temperatureto warm to RT
  9. customthe mixture was partitioned between water and EtOAc
  10. customthe phases separated
  11. extractionThe aqueous solution was extracted with EtOAc
  12. washThe combined EtOAc solutions were washed with 5% aqueous sodium bisulfite, saturated brine
  13. dry with materialdried over sodium sulfate
  14. concentrationconcentrated to dryness at reduced pressure
  15. customThe residue was subjected to HPLC purification (ACN: Water-0.1% Formic acid)

Sources & evidence

ORD record
ord-bd19b588c83842a49406767e5b0aa370
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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