Tetrahydrofuran → HCID 117737299, compound

HRID 1504468Notes

Reaction equation

HRID 1504468 reaction equation
[Br:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[CH:12]=[CH:11][C:10]2=[O:34])=[C:4]([O:35][CH3:36])[CH:3]=1.[O:37]1[CH:41]=[CH:40][C:39]([NH2:42])=[N:38]1.C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>Cl.CCOC(C)=O>[Br:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19]([NH:42][C:39]4[CH:40]=[CH:41][O:37][N:38]=4)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[CH:12]=[CH:11][C:10]2=[O:34])=[C:4]([O:35][CH3:36])[CH:3]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 18102163-Isoxazolamine2×HCID 2733832Lithium Hexamethyldisilazide2×HCID 117737171HCID 117737171, compound

Product 1

HCID 117737299HCID 117737299, compoundYield 91%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of perfluorophenyl 1-(4-bromo-2-methoxy-5-methylphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (3.508 g, 4.87 mmol), isoxazol-3-amine (0.540 ml, 7.31 mmol) and THF (48.7 ml) was cooled in an ice-bath for 15 min, then lithium bis(trimethylsilyl)amide (1M in THF) (12.18 ml, 12.18 mmol) was added dropwise. After 20 min, additional portions of 3-aminoisoxazole (0.1 mL) and LHMDS solution (2 mL) were added. After 5 min, the mixture was diluted with 1N aq. HCl and EtOAc. The layers were separated, and the organic layer was washed with 1N aq. HCl. The aq. layers were combined and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was concentrated from DCM, and then taken up in DCM. The resulting suspension was sonicated and filtered. The collected solid was washed with DCM (2×), dried under a stream of N2 (g), then dried under vacuum to give 1-(4-bromo-2-methoxy-5-methylphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (2.169 g, 4.42 mmol, 91% yield) as a white solid. 1 H NMR (400 MHz, DMSO-d6) □=11.66 (br. s., 1 H), 8.72 (d, J=1.8 Hz, 1 H), 8.35 (d, J=2.2 Hz, 1 H), 8.21 (d, J=9.6 Hz, 1 H), 7.83 (dd, J=2.2, 8.9 Hz, 1 H), 7.52 (s, 1 H), 7.34 (d, J=0.4 Hz, 1 H), 6.78 (d, J=9.6 Hz, 2 H), 6.43 (d, J=1.9 Hz, 1 H), 3.67 (s, 3 H); 2.31 (s, 3 H). m/z (ESI) 489.9 (M+H)+.

Workup

  1. waitAfter 5 min
  2. customThe layers were separated
  3. washthe organic layer was washed with 1N aq. HCl
  4. extractionextracted with EtOAc (2×)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. concentrationThe residue was concentrated from DCM
  9. customThe resulting suspension was sonicated
  10. filtrationfiltered
  11. washThe collected solid was washed with DCM (2×)
  12. dry with materialdried under a stream of N2 (g)
  13. customdried under vacuum

Sources & evidence

ORD record
ord-187bb2ad045d4487a45679c88ebbeaa8
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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