Dichloromethane → N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1-(2,3',5'-trifluoro-5-hydroxy-[1,1'-biphenyl]-4-yl)-1,2-dihydroquinoline-6-sulfonamide

HRID 1504376Notes

Reaction equation

HRID 1504376 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]([N:22]([C:32]4[CH:36]=[CH:35][O:34][N:33]=4)[CH2:23][C:24]4[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=4)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[CH:12]=[CH:11][C:10]2=[O:37])=[C:4]([OH:38])[CH:3]=1.[F:39][C:40]1[CH:41]=[C:42](B(O)O)[CH:43]=[C:44]([F:46])[CH:45]=1.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>CN(C=O)C.O>[O:34]1[CH:35]=[CH:36][C:32]([N:22]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[S:19]([C:15]2[CH:14]=[C:13]3[C:18](=[CH:17][CH:16]=2)[N:9]([C:5]2[C:4]([OH:38])=[CH:3][C:2]([C:42]4[CH:41]=[C:40]([F:39])[CH:45]=[C:44]([F:46])[CH:43]=4)=[C:7]([F:8])[CH:6]=2)[C:10](=[O:37])[CH:11]=[CH:12]3)(=[O:21])=[O:20])=[N:33]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 1177372691-(4-bromo-5-fluoro-2-hydroxyphenyl)-N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide

Product 1

HCID 117737313N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1-(2,3',5'-trifluoro-5-hydroxy-[1,1'-biphenyl]-4-yl)-1,2-dihydroquinoline-6-sulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1-(4-bromo-5-fluoro-2-hydroxyphenyl)-N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.037 g, 0.062 mmol) and (3,5-difluorophenyl)boronic acid (0.015 g, 0.092 mmol) in DMF (0.246 ml) and water (0.062 ml) was added potassium carbonate (0.026 g, 0.185 mmol) followed by PdCl2dppf, DCM adduct (2.255 mg, 3.08 μmol). The resulting mixture was heated to 50° C. and stirred for 2.5 hours. The solution was then cooled to room temperature and transferred to a sep. funnel containing water. The aqueous layer was washed 2× with DCM. The aqueous layer was subsequently neutralized and washed 3× with DCM. The organic layers were combined, dried with MgSO4, filtered and concentrated to an oil. The crude product was used without further purification assuming quantitative yield. m/z (ESI) 634.2 (M+H)+.

Workup

  1. temperatureThe solution was then cooled to room temperature
  2. washThe aqueous layer was washed 2× with DCM
  3. washwashed 3× with DCM
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to an oil
  7. customThe crude product was used without further purification

Sources & evidence

ORD record
ord-b1f713c4667b45f3a13c7b6c397df5e4
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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