Hydrochloric Acid → 1-(4-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide

HRID 1504419Notes

Reaction equation

HRID 1504419 reaction equation
[NH2:1][C:2]1[CH:6]=[CH:5][O:4][N:3]=1.[Br:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[C:23]3[C:18](=[CH:19][C:20]([S:24](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:26])=[O:25])=[CH:21][CH:22]=3)[CH:17]=[CH:16][C:15]2=[O:39])=[C:10]([O:40][CH3:41])[CH:9]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl>C1COCC1>[Br:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[C:23]3[C:18](=[CH:19][C:20]([S:24]([NH:1][C:2]4[CH:6]=[CH:5][O:4][N:3]=4)(=[O:26])=[O:25])=[CH:21][CH:22]=3)[CH:17]=[CH:16][C:15]2=[O:39])=[C:10]([O:40][CH3:41])[CH:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 18102163-IsoxazolamineHCID 2733832Lithium HexamethyldisilazideHCID 117737057(S)-Perfluorophenyl 1-(4-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate

Product 1

HCID 1177372221-(4-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamideYield 82.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-aminoisoxazole (0.664 ml, 8.98 mmol) and racemic perfluorophenyl 1-(4-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (4.705 g, 8.16 mmol) in 100 mL THF, was cooled to 0° C. LHMDS 1N in THF (17.15 ml, 17.15 mmol) was added dropwise. After stirring for an hour, HCl 1N aqueous (32.7 ml, 32.7 mmol) was added, and the reaction mixture was extracted with DCM. The organics were dried over MgSO4 and concentrated. The crude residue was triturated with ether, and the resulting solid was collected and dried yielding 1-(4-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (3.20 g, 6.72 mmol, 82% yield). A portion of this material was resolved. Chiral separation was performed by SFC: (S,S) Whelk-O, 50% isopropanol yielding (P)-1-(4-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.150 g, 0.315 mmol, 3.86% yield) and (M)-1-(4-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.154 g, 0.323 mmol, 3.96% yield). Analytical data for both isomers is identical. m/z (ESI) 476.1 (M+H)+. 1H NMR (ACETONITRILE-d3) δ: 8.37 (d, J=1.9 Hz, 1H), 8.23 (d, J=2.3 Hz, 1H), 7.97 (d, J=9.6 Hz, 1H), 7.78 (dd, J=8.9, 2.2 Hz, 1H), 7.43 (d, J=2.1 Hz, 1H), 7.34 (dd, J=8.3, 2.1 Hz, 1H), 7.16 (d, J=8.3 Hz, 1H), 6.71-6.79 (m, 2H), 6.45 (d, J=1.8 Hz, 1H), 3.69 (s, 3H).

Workup

  1. extractionthe reaction mixture was extracted with DCM
  2. dry with materialThe organics were dried over MgSO4
  3. concentrationconcentrated
  4. customThe crude residue was triturated with ether
  5. customthe resulting solid was collected
  6. customdried

Sources & evidence

ORD record
ord-4c71d1db7e914ea4b9fa231b7f3b560f
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

Loading…