Sodium Bicarbonate → 8-(4-Methyl-piperazin-1-yl)-3phenylsulfonylquinoline

HRID 2116529Notes

Reaction equation

HRID 2116529 reaction equation
I[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[N:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1.BrC1C=NC2C(C=1)=CC=CC=2N1CCN(C)CC1.O.O.[Na+].[C:40]1([S:46]([O-:48])=[O:47])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(=O)([O-])O.[Na+]>CN(C)C=O.[Cu]I.CO.ClCCl>[CH3:18][N:15]1[CH2:16][CH2:17][N:12]([C:6]2[CH:7]=[CH:8][CH:9]=[C:10]3[C:5]=2[N:4]=[CH:3][C:2]([S:46]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)(=[O:48])=[O:47])=[CH:11]3)[CH2:13][CH2:14]1

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 23681562Benzenesulfinic acid, sodium salt, dihydrateHCID 673136243-Bromo-8-(4-methyl-piperazin-1-yl)-quinolineHCID 673137463-Iodo-8-(4-methyl-piperazin-1-yl)-quinoline

Product 1

HCID 99291628-(4-Methyl-piperazin-1-yl)-3phenylsulfonylquinolineYield 7%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A 4:1 mixture of 3-iodo-8-(4-methyl-piperazin-1-yl)-quinoline (D2) and 3-bromo-8-(4-methyl-piperazin-1-yl)-quinoline (D1) (1.5 g), phenylsulfinic acid sodium salt dihydrate (2.52 g, 12.6 mmol) and copper (I) iodide (2.4 g, 12.6 mmol) in N,N-dimethylformamide (25 ml) was stirred in an oil bath at 120° C. for 40 h under argon. To the reaction mixture, cooled to ambient temperature, was added 5% sodium hydrogen carbonate solution (100 ml) and dichloromethane (100 ml) with vigorous shaking. The insoluble material was filtered, washed with dichloromethane (3×20 ml) and discarded. The filtrate and washings were transferred to a separating funnel and the layers separated. The aqueous layer was extracted with dichloromethane (100 ml) and the combined organic extracts were washed with water (100 ml), dried (MgSO4) and concentrated in vacuo to an oil (0.9 g). The oil was purified by chromatography over silica gel eluting with a gradient of methanol/dichloromethane to afford an orange oil (0.28 g, Rf 0.11, methanol/dichloromethane 1:19). This material was further purified by passage through a strong cation exchange (SCX) column eluting firstly with methanol (fractions discarded) and then with methanol/aqueous ammonia-880 (10:1) to give the title compound (D9) as an orange oil (0.152 g, 0.41 mmol, 7% over two steps);

Workup

  1. temperatureTo the reaction mixture, cooled to ambient temperature
  2. filtrationThe insoluble material was filtered
  3. washwashed with dichloromethane (3×20 ml)
  4. customThe filtrate and washings were transferred to a separating funnel
  5. customthe layers separated
  6. extractionThe aqueous layer was extracted with dichloromethane (100 ml)
  7. washthe combined organic extracts were washed with water (100 ml)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo to an oil (0.9 g)
  10. customThe oil was purified by chromatography over silica gel eluting with a gradient of methanol/dichloromethane
  11. customto afford an orange oil (0.28 g, Rf 0.11, methanol/dichloromethane 1:19)
  12. customThis material was further purified by passage through a strong cation exchange (SCX) column
  13. washeluting firstly with methanol (fractions discarded)

Sources & evidence

ORD record
ord-32ef83e37ad143d5b584f9871a36866c
Source dataset
uspto-grants-2008_10
Patent number
US07439244B2

Reaction notes

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