Water → 1,2-Benzisothiazole-3-carboxamide, N-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)-, hydrochloride, hydrate (2:2:1)

HRID 1885312Notes

Reaction equation

HRID 1885312 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.[S:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[C:15]([N:22]2[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][CH2:30][CH2:31][NH2:32])[CH2:24][CH2:23]2)=[N:14]1.C(N(CC)CC)C.O>C1(C)C=CC=CC=1>[ClH:12].[S:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[C:15]([N:22]2[CH2:23][CH2:24][N:25]([CH2:28][CH2:29][CH2:30][CH2:31][NH:32][C:10]([C:3]3[C:4]4[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=4[S:1][N:2]=3)=[O:11])[CH2:26][CH2:27]2)=[N:14]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 105654621-Piperazinebutanamine, 4-(1,2-benzisothiazol-3-yl)-HCID 15639471Benzo[d]isothiazole-3-carbonyl chloride

Product 1

HCID 30730691,2-Benzisothiazole-3-carboxamide, N-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)-, hydrochloride, hydrate (2:2:1)Yield 27.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 1,2-benzisothiazole-3-carboxylic acid chloride (2.6 g), 1-(1,2-benzisothiazol-3-yl)-4-(4-aminobutyl)piperazine (3.45 g), and triethylamine (5 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 added to water. The organic phase was separated and the aqueous phase was extracted with ethyl acetate. The ethyl acetate extracts and the toluene phase were combined and dried anhydrous over magnesium sulfate. The organic phase was filtered and the filtrate concentrated in vacuo. The residue was chromatographed on silica using ethyl acetate. The appropriate fractions were collected and concentrated in vacuo. The residue was taken up in ether and hydrogen chloride in ether was added. The precipitate was recrystallized from dichloromethane/ether and dried (0.1 mm mercury, refluxing isopropanol alcohol temperature) to provide 1.60 g (27.1%) of product, mp 203°-205° C.

Workup

  1. waitAfter 24 hr
  2. customThe organic phase was separated
  3. extractionthe aqueous phase was extracted with ethyl acetate
  4. filtrationThe organic phase was filtered
  5. concentrationthe filtrate concentrated in vacuo
  6. customThe residue was chromatographed on silica
  7. customThe appropriate fractions were collected
  8. concentrationconcentrated in vacuo
  9. additionhydrogen chloride in ether was added
  10. customThe precipitate was recrystallized from dichloromethane/ether
  11. customdried
  12. temperature(0.1 mm mercury, refluxing isopropanol alcohol temperature)

Sources & evidence

ORD record
ord-c64bfd68e001464fa3d45384951ce8fd
Source dataset
uspto-grants-1992_09
Patent number
US05143923

Reaction notes

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