Potassium Phosphate, Tribasic → HCID 86344134, compound

HRID 1504535Notes

Reaction equation

HRID 1504535 reaction equation
Br[C:2]1[C:7]([F:8])=[CH:6][C:5]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19]([NH:22][C:23]4[CH:27]=[CH:26][O:25][N:24]=4)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[N:12]=[CH:11][C:10]2=[O:28])=[C:4]([O:29][CH3:30])[CH:3]=1.[F:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C>[F:8][C:7]1[CH:6]=[C:5]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19]([NH:22][C:23]4[CH:27]=[CH:26][O:25][N:24]=4)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[N:12]=[CH:11][C:10]2=[O:28])[C:4]([O:29][CH3:30])=[CH:3][C:2]=1[C:35]1[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2856454-Fluorophenylboronic acidHCID 117737249HCID 117737249, compound

Product 1

HCID 86344134HCID 86344134, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 178482226HCID 178482226, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A vial was charged with 1-(4-bromo-5-fluoro-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoxaline-6-sulfonamide (201.5 mg, 0.407 mmol), (4-fluorophenyl)boronic acid (114 mg, 0.814 mmol), 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(ii) chloride (28.8 mg, 0.041 mmol), and potassium phosphate (259 mg, 1.221 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (1627 μl) and water (407 μl) were added. The vial was sealed and heated to 80° C. for 30 min. The mixture was cooled, the layers were separated, and the aq. layer was extracted with EtOAc. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was dissolved in MeOH and filtered through a 0.2 micron filter. The filtrate was purified by reverse-phase HPLC (25-70% CH3CN/H2O with 0.1% TFA). Fractions containing clean desired product were combined and lyophilized to give 1-(2,4′-difluoro-5-methoxy-4-biphenylyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinoxalinesulfonamide (107 mg, 82% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=11.76 (s, 1H), 8.76 (d, J=1.9 Hz, 1H), 8.50 (s, 1H), 8.32 (d, J=2.2 Hz, 1H), 7.95 (dd, J=2.3, 8.9 Hz, 1H), 7.76 (ddd, J=1.5, 5.4, 8.8 Hz, 2H), 7.56 (d, J=10.3 Hz, 1H), 7.46-7.37 (m, 3H), 7.01 (d, J=8.9 Hz, 1H), 6.49 (d, J=2.0 Hz, 1H), 3.80 (s, 3H). m/z (ESI) 511.0 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (1627 μl) and water (407 μl) were added
  3. customThe vial was sealed
  4. temperatureThe mixture was cooled
  5. customthe layers were separated
  6. extractionthe aq. layer was extracted with EtOAc
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in MeOH
  11. filtrationfiltered through a 0.2 micron
  12. filtrationfilter
  13. customThe filtrate was purified by reverse-phase HPLC (25-70% CH3CN/H2O with 0.1% TFA)
  14. additionFractions containing clean desired product

Sources & evidence

ORD record
ord-f489451541ee43ed8738e45e3b7b266d
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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