Hydrochloric Acid → HCID 117736975, compound

HRID 1504521Notes

Reaction equation

HRID 1504521 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:11]2[C:20]3[C:15](=[CH:16][C:17]([S:21](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:23])=[O:22])=[CH:18][CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:36])[C:5]([O:9][CH3:10])=[N:6][C:7]=1[Cl:8].[NH2:37][C:38]1[CH:42]=[CH:41][O:40][N:39]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Cl>CCCCCCC.C(Cl)Cl.CCOC(C)=O.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([N:11]2[C:20]3[C:15](=[CH:16][C:17]([S:21]([NH:37][C:38]4[CH:42]=[CH:41][O:40][N:39]=4)(=[O:22])=[O:23])=[CH:18][CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:36])[C:5]([O:9][CH3:10])=[N:6][C:7]=1[Cl:8]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 18102163-IsoxazolamineHCID 2733832Lithium HexamethyldisilazideHCID 117736991HCID 117736991, compound

Product 1

HCID 117736975HCID 117736975, compoundYield 80%

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×HCID 8900HeptaneSolvent

Conditions

Temperature
0 °C

Procedure

A 100-mL RBF was charged with perfluorophenyl 1-(5,6-dichloro-2-methoxypyridin-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (3.0 g, 5.29 mmol) then purged with nitrogen. THF (191 mL) and 3-aminoisoxazole (4.89 g, 5.82 mmol) were introduced and the resultant tan solution cooled to 0° C. A solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (1.0 M, 11.1 mL, 11.1 mmol) was added dropwise via syringe to the stirred reaction mixture over 5 min. After 15 min, 1.0 N HCl (25 mL) was introduced and the resultant reaction mixture was allowed to warm to RT. The mixture was diluted with and EtOAc (25 mL) and the layers were separated, and the aqueous layer was further extracted with EtOAc (3×25 mL). The combined organic layers were then washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then purified by flash column chromatography (100-g Biotage column, eluent: gradient, 0 to 100% EtOAc in heptane with 10% CH2Cl2 as an additive) to afford 1-(5,6-dichloro-2-methoxypyridin-3-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (1.97 g, 4.22 mmol, 80% yield) as a white amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ=8.62 (d, J=2.3 Hz, 1H), 8.47 (s, 1H), 8.28 (d, J=9.6 Hz, 1H), 7.94 (dd, J=2.3, 9.1 Hz, 1H), 7.19 (d, J=9.0 Hz, 1H), 6.91 (d, J=9.7 Hz, 1H), 3.82 (s, 3H). m/z (ESI) 468.9 (M+H)+.

Workup

  1. customthen purged with nitrogen
  2. customthe resultant reaction mixture
  3. temperatureto warm to RT
  4. customthe layers were separated
  5. extractionthe aqueous layer was further extracted with EtOAc (3×25 mL)
  6. washThe combined organic layers were then washed with brine (100 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was then purified by flash column chromatography (100-g Biotage column, eluent

Sources & evidence

ORD record
ord-0a3eec122b4e4414a6a959e384de824c
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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