Water → 1-[3-(4-(4-Fluorophenyl)piperazinyl)propyl]-5,6-dihydro(1H,4H)-1,2,5-thiadiazolo[4,3,2-ij]quinoline 2,2-dioxide

HRID 654096Notes

Reaction equation

HRID 654096 reaction equation
[NH:1]1[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH2:6][CH2:5][CH2:4][N:3]3[S:2]1(=[O:14])=[O:13].[H-].[Na+].Cl[CH2:18][CH2:19][CH2:20][N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[CH2:23][CH2:22]1.O>CN(C)C=O.C(OCC)(=O)C>[F:33][C:30]1[CH:29]=[CH:28][C:27]([N:24]2[CH2:23][CH2:22][N:21]([CH2:20][CH2:19][CH2:18][N:1]3[C:11]4=[C:12]5[C:7](=[CH:8][CH:9]=[CH:10]4)[CH2:6][CH2:5][CH2:4][N:3]5[S:2]3(=[O:13])=[O:14])[CH2:26][CH2:25]2)=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 106825561-(3-Chloropropyl)-4-(4-fluorophenyl)piperazineHCID 156467015,6-dihydro(1H,4H)-1,2,5-thiadiazolo[4,3,2-ij]quinoline 2,2-dioxide

Product 1

HCID 198884611-[3-(4-(4-Fluorophenyl)piperazinyl)propyl]-5,6-dihydro(1H,4H)-1,2,5-thiadiazolo[4,3,2-ij]quinoline 2,2-dioxideYield 65.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 5,6-dihydro(1H,4H)-1,2,5-thiadiazolo[4,3,2-ij]quinoline 2,2-dioxide (5.34 g) in dry N,N-dimethylformamide (50 cc) is added dropwise to a suspension of sodium hydride (0.72 g, 80% suspension in oil) in N,N-dimethylformamide (20 cc). After 15 minutes' stirring, 1-(3-chloropropyl)-4-(4-fluoro-phenyl)piperazine (7.68 g) is added. The reaction mixture is heated to 100° C. for 1 hour and 30 minutes and is then cooled and poured into a mixture of water (300 cc) and ethyl acetate (500 cm). The organic phase is washed with water (3×200 cc), is dried over magnesium sulphate and is concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (0.2-0.063-mm particle size, 6-cm diameter, 50-cm height) and eluted at a pressure of 0.7 bars of nitrogen with a mixture of cyclohexane and ethyl acetate (80-20 by volume), 125-cc fractions being collected. Fractions 10 to 28 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The solid obtained is recrystallized from ethanol (80 cc). 1-[3-(4-(4-Fluorophenyl)piperazinyl)propyl]-5,6-dihydro(1H,4H)-1,2,5-thiadiazolo[4,3,2-ij]quinoline 2,2-dioxide (7.2 g) is obtained, melting at 98° C.

Workup

  1. temperatureis then cooled
  2. washThe organic phase is washed with water (3×200 cc)
  3. dry with materialis dried over magnesium sulphate
  4. concentrationis concentrated to dryness under reduced pressure (2.7 kPa)
  5. customThe residue is chromatographed on a column of silica gel (0.2-0.063-mm particle size, 6-cm diameter, 50-cm height)
  6. washeluted at a pressure of 0.7 bars of nitrogen with a mixture of cyclohexane and ethyl acetate (80-20 by volume), 125-cc fractions
  7. custombeing collected
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  9. customThe solid obtained
  10. customis recrystallized from ethanol (80 cc)

Sources & evidence

ORD record
ord-5d8fcde864d54e1bab37e777f4cafd02
Source dataset
uspto-grants-1992_07
Patent number
US05130313

Reaction notes

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