Lithium Hexamethyldisilazide → 1-(5-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide

HRID 1504545Notes

Reaction equation

HRID 1504545 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:34][CH3:35])=[C:6]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:33])[CH:7]=1.[CH3:36][O:37][C:38]1[CH:50]=[CH:49][C:41]([CH2:42][NH:43][C:44]2[CH:48]=[CH:47][O:46][N:45]=2)=[CH:40][CH:39]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:34][CH3:35])=[C:6]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([N:43]([C:44]4[CH:48]=[CH:47][O:46][N:45]=4)[CH2:42][C:41]4[CH:40]=[CH:39][C:38]([O:37][CH3:36])=[CH:50][CH:49]=4)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:33])[CH:7]=1

Participants

4

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 82671591N-[(4-methoxyphenyl)methyl]-1,2-oxazol-3-amineHCID 117736973Perfluorophenyl 1-(5-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate

Product 1

HCID 1177371841-(5-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamideYield 70.1%

Conditions

Temperature
0 °C

Procedure

A flask containing perfluorophenyl 1-(5-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (3.65 g, 6.33 mmol) and N-(4-methoxybenzyl)isoxazol-3-amine (1.358 g, 6.65 mmol) was flushed with nitrogen and then charged with THF (63.3 ml) and cooled to 0° C. Lithium bis(trimethylsilyl)amide (1.0M in THF) (6.97 ml, 6.97 mmol) was added slowly, and the solution was stirred at 0° C. for 45 minutes until complete consumption of starting material. The reaction was quenched with water and extracted (×3) with EtOAc. The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude solid was triturated in IPA and filtered, washing well with IPA, to yield 1-(5-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (2.65 g, 4.44 mmol, 70.1% yield) as a white solid. m/z (ESI) 596.0 (M+H)+.

Workup

  1. customwas flushed with nitrogen
  2. additioncharged with THF (63.3 ml)
  3. customThe reaction was quenched with water
  4. extractionextracted (×3) with EtOAc
  5. washThe combined organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude solid was triturated in IPA
  10. filtrationfiltered
  11. washwashing well with IPA

Sources & evidence

ORD record
ord-51dbc7ee6c1441548a6df8abe2fe8946
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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