Dichloromethane → HCID 117737249, compound

HRID 1504552Notes

Reaction equation

HRID 1504552 reaction equation
[Br:1][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](Cl)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[N:12]=[CH:11][C:10]2=[O:23])=[C:4]([O:24][CH3:25])[CH:3]=1.ClCCl.[NH2:29][C:30]1[CH:34]=[CH:33][O:32][N:31]=1>N1C=CC=CC=1>[Br:1][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]([NH:29][C:30]4[CH:34]=[CH:33][O:32][N:31]=4)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[N:12]=[CH:11][C:10]2=[O:23])=[C:4]([O:24][CH3:25])[CH:3]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 18102163-IsoxazolamineHCID 117737197HCID 117737197, compound

Product 1

HCID 117737249HCID 117737249, compoundYield 82.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A RBF was charged with 1-(4-bromo-5-fluoro-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoxaline-6-sulfonyl chloride (512.8 mg, 1.031 mmol), dichloromethane (1718 μl), and 3-aminoisoxazole (114 μl, 1.546 mmol) to give a thick suspension. Pyridine (3437 μl) was added relatively quickly, leading to thinner suspension. After 2 h, the mixture was concentrated in vacuo. The residue was partitioned between EtOAc and 2N aq. HCl. The layers were separated, and 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 on silica gel (50-g SNAP Ultra column, 0-50% 3:1 EtOAc/EtOH in heptane with 10% DCM) to give 1-(4-bromo-5-fluoro-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoxaline-6-sulfonamide (419.2 mg, 0.846 mmol, 82% yield) as a white foam. 1H NMR (400 MHz, DMSO-d6) δ=11.74 (br. s., 1H), 8.74 (d, J=1.9 Hz, 1H), 8.47 (s, 1H), 8.29 (d, J=2.2 Hz, 1H), 7.90 (dd, J=2.2, 8.9 Hz, 1H), 7.72 (d, J=6.1 Hz, 1H), 7.62 (d, J=8.4 Hz, 1H), 6.98 (d, J=8.8 Hz, 1H), 6.48 (d, J=1.9 Hz, 1H), 3.74-3.71 (m, 3H), 3.32 (s, 3H). m/z (ESI) 495.0 (M+H)+.

Workup

  1. customto give a thick suspension
  2. concentrationthe mixture was concentrated in vacuo
  3. customThe residue was partitioned between EtOAc and 2N aq. HCl
  4. customThe layers were separated
  5. extractionthe aq. layer was extracted with EtOAc (2×)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (50-g SNAP Ultra column, 0-50% 3:1 EtOAc/EtOH in heptane with 10% DCM)

Sources & evidence

ORD record
ord-5614beedcc8d4b53aff9d2cbf1aad3e4
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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