Water → N-[4-(1-(2-Methoxyphenyl)-4-piperazinyl)butyl]-1,2-benzisothiazole-3-carboxamide dihydrochloride

HRID 1885311Notes

Reaction equation

HRID 1885311 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([C:10]([Cl:12])=[O:11])=[N:2]1.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N:21]1[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][CH2:29][CH2:30][NH2:31])[CH2:23][CH2:22]1.C(N(CC)CC)C.O>C1(C)C=CC=CC=1>[ClH:12].[ClH:12].[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N:21]1[CH2:22][CH2:23][N:24]([CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:10]([C:3]2[C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[S:1][N:2]=2)=[O:11])[CH2:25][CH2:26]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 109999031-(4-Aminobutyl)-4-(2-methoxyphenyl)piperazineHCID 15639471Benzo[d]isothiazole-3-carbonyl chloride

Product 1

HCID 19752300N-[4-(1-(2-Methoxyphenyl)-4-piperazinyl)butyl]-1,2-benzisothiazole-3-carboxamide dihydrochlorideYield 69.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 1,2-benzisothiazole-3-carboxylic acid chloride (2.44 g), 1-(2-methoxyphenyl)-4-(4-aminobutyl)piperazine (3.26 g), and triethylamine (6 ml), in sieve-dried toluene (100 ml) was heated to 80° C., with stirring, overnight. After 24 hr, the reaction mixture was cooled to room temperature and poured into water. The organic phase was separated and the aqueous phase was extracted with ether. The ether extracts and toluene phase were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The residue was chromatographed on silica using ethyl acetate as the eluent. The appropriate fractions were collected and concentrated. The residue was taken up in ether and ethereal hydrogen chloride was added. The precipitate was recrystallized from ethanol/ethyl acetate and dried (0.1 mm mercury, refluxing toluene temperature) to provide 2.13 g (34.6%) of product, mp 174°-178° C.

Workup

  1. waitAfter 24 hr
  2. customThe organic phase was separated
  3. extractionthe aqueous phase was extracted with ether
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe residue was chromatographed on silica
  8. customThe appropriate fractions were collected
  9. concentrationconcentrated
  10. additionethereal hydrogen chloride was added
  11. customThe precipitate was recrystallized from ethanol/ethyl acetate
  12. customdried
  13. temperature(0.1 mm mercury, refluxing toluene temperature)

Sources & evidence

ORD record
ord-a85c9cce09b641fca63da3256bf65bd8
Source dataset
uspto-grants-1992_09
Patent number
US05143923

Reaction notes

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