Hydrochloric Acid → HCID 178470118, compound

HRID 1640942Notes

Reaction equation

HRID 1640942 reaction equation
S.[Na].[CH2:3]([O:5][C:6]([C:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][C:13]([Br:20])=[C:14]([F:19])[CH:15]=2)[N:10]([CH:21]2[CH2:23][CH2:22]2)[C:9]=1[S:24]C)=[O:7])[CH3:4].Cl>C1COCC1.O.CN(C=O)C>[CH2:3]([O:5][C:6]([C:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][C:13]([Br:20])=[C:14]([F:19])[CH:15]=2)[N:10]([CH:21]2[CH2:22][CH2:23]2)[C:9]=1[SH:24])=[O:7])[CH3:4]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 599995377-Bromo-1-cyclopropyl-6-fluoro-2-methylsulfanyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl esterHCID 86586439Sodium hydrogen sulphide2×

Product 1

HCID 178470118HCID 178470118, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

Sodium hydrogen sulfide (5 mg, 0.09 mmole, 1.5 equiv.) is added to a stirred solution of 7-Bromo-1-cyclopropyl-6-fluoro-2-methylsulfanyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (5, 24 mg, 0.06 mmole) in THF (tetrahydrofuran, 2 ml) under argon at room temperature. The reaction is then stirred at 45° C. until TLC indicated completion. The reaction mixture is diluted with water and washed with diethyl ether. The aqueous layer is acidified by 1N HCl to a pH of approximately 2, and extracted with EtOAc. The resulting organics are washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude product is purified by PTLC (20% CH3OH in CHCl3) to give 6. Alternatively, sodium hydrogen sulfide (20 mg, 0.36 mmole, 1.5 equiv.) is added to a stirred solution of 5 (crude, 96 mg, 0.24 mmole) in DMF (6 ml) under argon at room temperature. The reaction is then stirred at 40° C. until TLC indicates completion. The reaction mixture is diluted with water, acidified by 1N HCl to a pH of approximately 2, and extracted with EtOAc. The resulting organics are washed with brine, dried over Na2SO4, and concentrated. The crude is purified by PTLC (20% CH3OH in CHCl3) to yield 6. 1H NMR (CDCl3) δ: 8.40 (d, 1H), 8.06 (d, 1H), 4.71 (q, 2H), 3.46 (m, 1H), 1.68 (m, 7H).

Workup

  1. washwashed with diethyl ether
  2. extractionextracted with EtOAc
  3. washThe resulting organics are washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified by PTLC (20% CH3OH in CHCl3)
  7. customto give 6
  8. stirringThe reaction is then stirred at 40° C. until TLC
  9. extractionextracted with EtOAc
  10. washThe resulting organics are washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. customThe crude is purified by PTLC (20% CH3OH in CHCl3)
  14. customto yield 6

Sources & evidence

ORD record
ord-18c45434015841719ec4e8a5423ec966
Source dataset
uspto-grants-2012_02
Patent number
US08114888B2

Reaction notes

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