Ammonium Chloride → 1-(4-bromo-5-fluoro-2-hydroxyphenyl)-N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide

HRID 1504374Notes

Reaction equation

HRID 1504374 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][NH:8][C:9]2[CH:13]=[CH:12][O:11][N:10]=2)=[CH:5][CH:4]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Br:26][C:27]1[C:32]([F:33])=[CH:31][C:30]([N:34]2[C:43]3[C:38](=[CH:39][C:40]([S:44](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:46])=[O:45])=[CH:41][CH:42]=3)[CH:37]=[CH:36][C:35]2=[O:59])=[C:29]([OH:60])[CH:28]=1.[Cl-].[NH4+]>C1COCC1.O.CC(C)=O>[Br:26][C:27]1[C:32]([F:33])=[CH:31][C:30]([N:34]2[C:43]3[C:38](=[CH:39][C:40]([S:44]([N:8]([C:9]4[CH:13]=[CH:12][O:11][N:10]=4)[CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:15][CH:14]=4)(=[O:45])=[O:46])=[CH:41][CH:42]=3)[CH:37]=[CH:36][C:35]2=[O:59])=[C:29]([OH:60])[CH:28]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 82671591N-[(4-methoxyphenyl)methyl]-1,2-oxazol-3-amineHCID 117737059Perfluorophenyl 1-(4-bromo-5-fluoro-2-hydroxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate

Product 1

HCID 1177372691-(4-bromo-5-fluoro-2-hydroxyphenyl)-N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of N-(4-methoxybenzyl)isoxazol-3-amine (3.37 g, 16.49 mmol) in THF (30.0 ml) was cooled to −78° C. LHMDS (15.74 ml, 15.74 mmol) was then added dropwise and the acetone/dryice bath was removed for 5 minutes. The solution was then returned to −78° C. and a solution of perfluorophenyl 1-(4-bromo-5-fluoro-2-hydroxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (4.35 g, 7.50 mmol) in THF (30.0 ml) was added dropwise. The resulting solution was stirred for 4 hours warming to room temperature. Saturated ammonium chloride was added to the reaction mixture. The resulting mixture was transferred to a sep. funnel containing water and the aqueous layer was washed 3× with EtOAc. The organic layers were combined, dried with MgSO4, filtered and concentrated to an oil. The crude product was purified by ISCO MPLC (100% heptanes to 60% 3:1 EtOAc:EtOH). The product eluted at 50% 3:1 EtOAc:EtOH. m/z (ESI) 602.1 (M+1)±.

Workup

  1. customwas removed for 5 minutes
  2. customwas then returned to −78° C.
  3. washthe aqueous layer was washed 3× with EtOAc
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to an oil
  7. customThe crude product was purified by ISCO MPLC (100% heptanes to 60% 3:1 EtOAc:EtOH)
  8. washThe product eluted at 50% 3:1 EtOAc

Sources & evidence

ORD record
ord-1621a67f09104d7793a410a55b42abbf
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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