Sodium hydride → 2-[3-(4-Phenyl-1,2,3,6-tetrahydropyridyl)propyl]-2H-isothiazolo[3,4,5-de]isoquinoline 1,1-dioxide

HRID 1087494Notes

Reaction equation

HRID 1087494 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH:9]=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.[Na].[S:18]1(=[O:31])(=[O:30])[C:28]2[C:29]3[C:24]([CH:25]=[CH:26][CH:27]=2)=[CH:23][N:22]=[CH:21][C:20]=3[NH:19]1.BrC1C2C(=CC=CC=2S(N)(=O)=O)C=NC=1.[H-].[Na+]>CN(C)C=O.C(OCC)(=O)C.O>[C:11]1([C:8]2[CH2:7][CH2:6][N:5]([CH2:4][CH2:3][CH2:2][N:19]3[C:20]4[CH:21]=[N:22][CH:23]=[C:24]5[CH:25]=[CH:26][CH:27]=[C:28]([C:29]=45)[S:18]3(=[O:31])=[O:30])[CH2:10][CH:9]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

9

Reactant 5

HCID 24758Sodium hydrideHCID 5360545SodiumHCID 98375831-(3-Chloropropyl)-4-phenyl-1,2,3,6-tetrahydropyridineHCID 14580059HCID 14580059, compoundHCID 14580061HCID 14580061, compound

Product 1

HCID 679223572-[3-(4-Phenyl-1,2,3,6-tetrahydropyridyl)propyl]-2H-isothiazolo[3,4,5-de]isoquinoline 1,1-dioxide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 1-(3-chloropropyl)-4-phenyl-1,2,3,6-tetrahydropyridine (4.9 g) in dimethylformamide (20 cc) is added to a solution of the sodium salt of 2H-isothiazolo[3,4,5-de]isoquinoline 1,1-dioxide (obtained by heating, after the evolution of gas has ceased, a solution of 4-bromo-5-isoquinolylsulphonamide (4.1 g) in dimethylformamide (25 cc) and a suspension of sodium hydride (0.85 g) in an 80% dispersion in vaseline oil in dimethylformamide (50 cc) at 110° C. for 2 hours and 30 minutes) cooled to 20° C. The reaction medium is heated for 2 hours at 100° C., then poured into a mixture of water (300 cc) and ethyl acetate (300 cc). The organic phase is washed with water (3×300 cc), dried over magnesium sulphate and concentrated to dryness. The residue is purified by chromatography on a silica column under a slight overpressure of nitrogen, eluting with ethyl acetate and then with a mixture of ethyl acetate and ethanol vol). 2-[3-(4-Phenyl-1,2,3,6-tetrahydropyridyl)propyl]-2H-isothiazolo[3,4,5-de]isoquinoline 1,1-dioxide (1.4 g) is obtained in the form of a yellow oil. 1.8 g of this product are purified with a second, similar chromatography stage to give 2-[3-(4-phenyl-1,2,3,6-tetrahydropyridyl)propyl]-2H-isothiazolo[3,4,5-de]isoquinoline 1,1-dioxide (1.6 g) (Rf =0.27; support: silica gel; eluant: ethyl acetate-ethanol (9-1 vol)). This product is dissolved in ethyl acetate (100 cc) before adding a 3 N solution of hydrochloric acid in isopropyl oxide (5 cc). The precipitate is centrifuged, washed with ethyl acetate and dried under vacuum (0.1 mm Hg) at 35° C. 2-[3-(4-Phenyl-1,2,3,6-tetrahydropyridyl)propyl]-2H-isothiazolo[3,4,5-de]isoquinoline 1,1-dioxide dihydrochloride (1.6 g) is obtained in the form of a yellow (amorphous) solid.

Workup

  1. customobtained
  2. temperatureby heating
  3. temperatureThe reaction medium is heated for 2 hours at 100° C.
  4. washThe organic phase is washed with water (3×300 cc)
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated to dryness
  7. customThe residue is purified by chromatography on a silica column under a slight overpressure of nitrogen
  8. washeluting with ethyl acetate
  9. additionwith a mixture of ethyl acetate and ethanol vol)

Sources & evidence

ORD record
ord-da779bf03b4f467e81c4b0d2d0ba67aa
Source dataset
uspto-grants-1991_07
Patent number
US05036075

Reaction notes

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