Methyl iodide → 2-{3-[4-(4-Fluorophenyl)-1-piperazinyl]-2-methoxypropyl)naphtho[1,8-cd]isothiazole 1,1-dioxide

HRID 1087519Notes

Reaction equation

HRID 1087519 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH:15]([OH:31])[CH2:16][N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[C:25]5[CH:26]=[CH:27][CH:28]=[C:19]([C:20]=45)[S:18]3(=[O:30])=[O:29])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:34]I>CN(C)C=O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH:15]([O:31][CH3:34])[CH2:16][N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[C:25]5[CH:26]=[CH:27][CH:28]=[C:19]([C:20]=45)[S:18]3(=[O:29])=[O:30])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 147267882-(3-[4-(4-Fluorophenyl)-1-piperazinyl]-2-hydroxypropyl}naphtho[1,8-cd]isothiazole 1,1-dioxide

Product 1

HCID 147267952-{3-[4-(4-Fluorophenyl)-1-piperazinyl]-2-methoxypropyl)naphtho[1,8-cd]isothiazole 1,1-dioxide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
20 °C

Procedure

A solution of 2-{3-[4-(4-fluorophenyl)-1-piperaziny]-2-hydroxypropyl}naphtho[1,8-cd]isothiazole 1,1-dioxide (4.41 g) in dimethylformamide (50 cc) is poured over 30 minutes into a mixture of sodium hydride (0.53 g) in a 50% dispersion in vaseline oil, and dimethylformamide (10 cc), under a current of argon, maintaining the temperature between 20° and 30° C. The reaction medium is stirred for 1 hour at temperature of about 20° C. and then methyl iodide (0.7 cc) is added over 10 minutes. Stirring is maintained for 15 hours at a temperature of about 20° C. The mixture is redissolved in distilled water (200 cc) and the organic phase is extracted with dichloromethane (4×100 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 is purified by flash-chromatography on a silica column, under a current of argon at medium pressure (0.5-1.5 bar) with ethyl acetate as eluant, and recrystallized from boiling acetonitrile (10 cc). 2-{3-[4-(4-Fluorophenyl)-1-piperazinyl]-2-methoxypropyl)naphtho[1,8-cd]isothiazole 1,1-dioxide (2.1 g) is obtained, m.p. 128° C.

Workup

  1. temperatureunder a current of argon, maintaining the temperature between 20° and 30° C
  2. stirringStirring
  3. temperatureis maintained for 15 hours at a temperature of about 20° C
  4. extractionthe organic phase is extracted with dichloromethane (4×100 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 is purified by flash-chromatography on a silica column
  9. customunder a current of argon at medium pressure (0.5-1.5 bar) with ethyl acetate as eluant, and recrystallized

Sources & evidence

ORD record
ord-6d56cbeedab541ffa126131a80569e0f
Source dataset
uspto-grants-1991_07
Patent number
US05036075

Reaction notes

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