Potassium Carbonate → 1-(2,3'-difluoro-5-methyl-[1,1'-biphenyl]-4-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide

HRID 1504450Notes

Reaction equation

HRID 1504450 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)[CH:12]=[CH:11][C:10]2=[O:28])=[C:4]([CH3:29])[CH:3]=1.[F:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[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)[CH:12]=[CH:11][C:10]2=[O:28])[C:4]([CH3:29])=[CH:3][C:2]=1[C:35]1[CH:34]=[CH:33][CH:32]=[C:31]([F:30])[CH:36]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 1177372241-(4-bromo-5-fluoro-2-methylphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide

Product 1

HCID 1177370071-(2,3'-difluoro-5-methyl-[1,1'-biphenyl]-4-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamideYield 56.5%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

A vial was charged with 1-(4-bromo-5-fluoro-2-methylphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (307 mg, 0.642 mmol), (3-fluorophenyl)boronic acid (117 mg, 0.834 mmol), potassium carbonate (266 mg, 1.926 mmol), and Pd(PPh3)4 (37.1 mg, 0.032 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (2407 μl) and water (802 μl) were added. The vial was sealed and heated to 90° C. for 19 h. The reaction was cooled down to rt. The whole was extracted with EtOAc (3×25-mL). The organic layer was separated, combined, dried over MgSO4, filtered, and concentrated to afford colorless residue. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 70% EtOAc in heptane, to provide 1-(2,3′-difluoro-5-methyl-[1,1′-biphenyl]-4-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (179 mg, 56.5% yield) as off-white solid. m/z (ESI) [M+H]+=493.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.91 (s, 3 H) 6.44 (d, J=1.87 Hz, 1 H) 6.80 (d, J=9.02 Hz, 1 H) 6.85 (d, J=9.64 Hz, 1 H) 7.26-7.37 (m, 1 H) 7.44-7.54 (m, 3 H) 7.54-7.64 (m, 1 H) 7.75 (d, J=8.40 Hz, 1 H) 7.88 (dd, J=8.97, 2.23 Hz, 1 H) 8.28 (d, J=9.64 Hz, 1 H) 8.41 (d, J=2.18 Hz, 1 H) 8.71 (d, J=1.76 Hz, 1 H) 11.68 (s, 1 H).

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (2407 μl) and water (802 μl) were added
  3. customThe vial was sealed
  4. temperatureThe reaction was cooled down to rt
  5. extractionThe whole was extracted with EtOAc (3×25-mL)
  6. customThe organic layer was separated
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford colorless residue
  11. customThe crude material was absorbed onto a plug of silica gel
  12. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  13. washeluting with a gradient of 0% to 70% EtOAc in heptane

Sources & evidence

ORD record
ord-2040ea27018d4ede85b93d2c9a1397b7
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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