Tetrahydrofuran → HCID 117736838, compound

HRID 1504480Notes

Reaction equation

HRID 1504480 reaction equation
[Br:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([N:10]2[C:19]3[C:14](=[CH:15][C:16]([S:20](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:22])=[O:21])=[CH:17][CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:35])=[C:4]([O:36][CH3:37])[CH:3]=1.[O:38]1[CH:42]=[CH:41][C:40]([NH2:43])=[N:39]1.C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CCOC(C)=O>[Br:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([N:10]2[C:19]3[C:14](=[CH:15][C:16]([S:20]([NH:43][C:40]4[CH:41]=[CH:42][O:38][N:39]=4)(=[O:21])=[O:22])=[CH:17][CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:35])=[C:4]([O:36][CH3:37])[CH:3]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 18102163-IsoxazolamineHCID 2733832Lithium HexamethyldisilazideHCID 117737274HCID 117737274, compound

Product 1

HCID 117736838HCID 117736838, compoundYield 67.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A RBF was charged with perfluorophenyl 1-(4-bromo-5-cyano-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (330.64 mg, 0.550 mmol), isoxazol-3-amine (46.7 μl, 0.632 mmol) and THF (3666 μl) to give a clear solution. The flask was cooled in an ice-water bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (1155 μl, 1.155 mmol) was added dropwise. After 15 min, the mixture was diluted with EtOAc and washed with 1N aq. HCl. The aq. layer was extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography (45-g Redi-Sep column, 25-g silica gel loading column, 0-5% MeOH/DCM) to give 1-(4-bromo-5-cyano-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (185 mg, 0.369 mmol, 67.1% yield) as a light-yellow solid. 1 H NMR (400 MHz, DMSO-d6) □=11.67 (br. s., 1 H), 8.73 (d, J=1.8 Hz, 1 H), 8.38 (d, J=2.2 Hz, 1 H), 8.27-8.21 (m, 1 H), 8.12-8.06 (m, 1 H), 7.90-7.78 (m, 2 H), 6.90 (d, J=9.0 Hz, 1 H), 6.85-6.76 (m, 1 H), 6.45 (d, J=1.8 Hz, 1 H), 3.81 (s, 3 H). m/z/(ESI) 501.0 (M+H)+.

Workup

  1. customto give a clear solution
  2. temperatureThe flask was cooled in an ice-water bath for 10 min
  3. washwashed with 1N aq. HCl
  4. extractionThe aq. layer was extracted with EtOAc (2×)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography (45-g Redi-Sep column, 25-g silica gel loading column, 0-5% MeOH/DCM)

Sources & evidence

ORD record
ord-2c08ce8b9c5446c898930b43111a907c
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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