Hydrochloric Acid → HCID 15870841, compound

HRID 1584823Notes

Reaction equation

HRID 1584823 reaction equation
[C:1]1([CH3:20])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[C:15](Br)[CH:16]=3)[CH2:11]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[CH:21]1([N:24]2[C:33]3[C:28](=[CH:29][C:30]([F:48])=[C:31]([Sn](CCCC)(CCCC)CCCC)[C:32]=3[CH3:34])[C:27](=[O:49])[C:26]([C:50]([O:52][CH2:53][CH3:54])=[O:51])=[CH:25]2)[CH2:23][CH2:22]1.C(OCC)(=O)C.Cl>CN(C)C=O.[Ag-]=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH:21]1([N:24]2[C:33]3[C:28](=[CH:29][C:30]([F:48])=[C:31]([C:15]4[CH:16]=[C:17]5[C:12](=[CH:13][CH:14]=4)[CH2:11][N:10]([S:7]([C:4]4[CH:5]=[CH:6][C:1]([CH3:20])=[CH:2][CH:3]=4)(=[O:9])=[O:8])[CH2:18]5)[C:32]=3[CH3:34])[C:27](=[O:49])[C:26]([C:50]([O:52][CH2:53][CH3:54])=[O:51])=[CH:25]2)[CH2:22][CH2:23]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 151678985-Bromo-2-(p-tolylsulfonyl)isoindolineHCID 15870852HCID 15870852, compound

Product 1

HCID 15870841HCID 15870841, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 178418778HCID 178418778, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

In 25 ml of N,N-dimethylformamide was dissolved 2.30 g of 2-(p-toluenesulfonyl)-5-bromoisoindoline, and 1.51 g of silver (I) oxide and 0.75 g of tetrakis(triphenylphosphine)palladium (0) were added to the solution, after which the resulting mixture was stirred at 100° C. for five minutes under a nitrogen atmosphere. Subsequently, to this reaction mixture was added 1.54 g of ethyl 1-cyclopropyl-6-fluoro-8-methyl-7-tributylstannyl-1,4-dihydro-4-oxoquinoline-3-carboxylate dissolved in 5 ml of N,N-dimethylformamide, and resulting mixture was stirred at 100° C. for 15 minutes. The reaction mixture was added to a mixed solvent of 50 ml of ethyl acetate and 100 ml of water, and the pH was adjusted to 2 with 2N hydrochloric acid, after which insolubles were removed by filtration. The organic layer formed was separated, washed with a saturated saline solution and then dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure. The residue obtained was purified by a column chromatography (eluent: toluene:ethyl acetate=3:1), and diethyl ether was thereafter added thereto, after which the crystals formed were collected by filtration, to obtain 0.55 g of colorless, crystalline ethyl 1-cyclopropyl-6-fluoro-8-methyl-7-[2-(p-toluenesulfonyl)isoindolin-5-yl]-1,4-dihydro-4-oxoquinoline-3-carboxylate.

Workup

  1. additionwere added to the solution
  2. customresulting mixture
  3. stirringwas stirred at 100° C. for 15 minutes
  4. customafter which insolubles were removed by filtration
  5. customThe organic layer formed
  6. customwas separated
  7. washwashed with a saturated saline solution
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solvent was then removed by distillation under reduced pressure
  10. customThe residue obtained
  11. customwas purified by a column chromatography (eluent: toluene:ethyl acetate=3:1), and diethyl ether
  12. additionwas thereafter added
  13. customafter which the crystals formed
  14. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-5bd2e2bf4a144caab112d3ab929c655b
Source dataset
uspto-grants-1999_08
Patent number
US05935952

Reaction notes

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