Water → HCID 54516061, compound

HRID 1196604Notes

Reaction equation

HRID 1196604 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH:12]1[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][N:20]2[C:24]3[CH:25]=[CH:26][CH:27]=[C:28]4[CH:29]=[CH:30][CH:31]=[C:22]([C:23]=34)[S:21]2(=[O:33])=[O:32])[CH2:14][CH2:13]1.[H-].[Na+].[CH3:36]I.O>CN(C)C=O.O1CCOCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:36])[CH:6]=[C:5]2[CH2:11][CH:12]1[CH2:13][CH2:14][N:15]([CH2:18][CH2:19][N:20]2[C:24]3[CH:25]=[CH:26][CH:27]=[C:28]4[CH:29]=[CH:30][CH:31]=[C:22]([C:23]=34)[S:21]2(=[O:32])=[O:33])[CH2:16][CH2:17]1

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 15646689HCID 15646689, compound

Product 1

HCID 54516061HCID 54516061, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of 2-{2-[4-((5-fluoro-3-indolyl)methyl)piperidino]ethyl}naphtho[1,8-cd]isothiazole 1,1-dioxide (2.3 g) in dimethylformamide (40 cc) is added in the course of 15 minutes to a 50% strength dispersion of sodium hydride (0.27 g) in liquid paraffin, under a stream of argon, while the temperature is maintained in the region of 20° C. The reaction medium is stirred for 1 hour at a temperature in the vicinity of 20° C. and a solution of methyl iodide (0.4 cc) in dioxane (20 cc) is then added in the course of 15 minutes. Stirring is maintained for 15 hours at a temperature in the vicinity of 20° C. The reaction mixture is taken up with distilled water (25 cc) and the organic phase is extracted with dichloromethane (4×50 cc), then washed with distilled water (25 cc), dried over anhydrous magnesium sulphate, filtered and concentrated to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa). The residue obtained is purified by flash chromatography on a silica column under a stream of argon at moderate pressure (0.5-1.5 bar) with dichloromethane and then a mixture of ethyl acetate and methanol (97:3 by volume) as eluent. 2-{2-[4-((5-Fluoro-1-methyl-3-indolyl)methyl)piperidino]ethyl} naphtho[1,8-cd]isothiazole 1,1-dioxide (0.8 g) is obtained in the form of a yellow oil, which is converted to an acid oxalate, m.p. 150°-152° C.

Workup

  1. stirringStirring
  2. temperatureis maintained for 15 hours at a temperature in the vicinity of 20° C
  3. extractionthe organic phase is extracted with dichloromethane (4×50 cc)
  4. washwashed with distilled water (25 cc)
  5. dry with materialdried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa)
  8. customThe residue obtained
  9. customis purified by flash chromatography on a silica column under a stream of argon at moderate pressure (0.5-1.5 bar) with dichloromethane
  10. additiona mixture of ethyl acetate and methanol (97:3 by volume) as eluent

Sources & evidence

ORD record
ord-8a26cd72793a44f688361e6b2090cd14
Source dataset
uspto-grants-1992_05
Patent number
US05114949

Reaction notes

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