3-(1-Piperazinyl)-1,2-benzisothiazole → 2-[4-(1,2-Benzisothiazol-3-yl)-1-piperazinylmethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one

HRID 362251Notes

Reaction equation

HRID 362251 reaction equation
C1(C)C=CC(S(O[CH2:11][C@@H:12]2[O:25][C:16]3=[C:17]4[C:21](=[CH:22][CH:23]=[C:15]3[O:14][CH2:13]2)[NH:20][C:19](=[O:24])[CH2:18]4)(=O)=O)=CC=1.[S:27]1[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[C:29]([N:36]2[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)=[N:28]1>CS(C)=O.C(OCC)(=O)C.CCCCCC>[S:27]1[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[C:29]([N:36]2[CH2:37][CH2:38][N:39]([CH2:11][CH:12]3[O:25][C:16]4=[C:17]5[C:21](=[CH:22][CH:23]=[C:15]4[O:14][CH2:13]3)[NH:20][C:19](=[O:24])[CH2:18]5)[CH2:40][CH2:41]2)=[N:28]1

Participants

5

Reactant 2

HCID 27721443-(1-Piperazinyl)-1,2-benzisothiazoleHCID 15381104(R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one

Product 1

HCID 699552932-[4-(1,2-Benzisothiazol-3-yl)-1-piperazinylmethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

(R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one (1.0 g, 2.7 mmole) and 1-(1,2-benzisothiazol-3-yl)piperazine (2.2 g, 10 mmole) are combined in 30 ml of dry DMSO and heated at 80°-90° C. for 4 hours under an argon atmosphere. After cooling to room temperature, the mixture is diluted with 500 ml of 1:1 ethyl acetate/hexane and washed with 250 ml of saturated aqueous sodium bicarbonate and with two 250 ml portions of water, dried over sodium sulfate, filtered and concentrated in vacuum. The residue is column chromatographed on silica gel using 0.5% methanol/CHCl3 as eluant to give the free base of the title compound. The product is crystallized from ethanol with the addition of one equivalent of fumaric acid to give the (S) enantiomer of the title compound as a fumarate salt.

Workup

  1. temperatureheated at 80°-90° C. for 4 hours under an argon atmosphere
  2. washwashed with 250 ml of saturated aqueous sodium bicarbonate and with two 250 ml portions of water
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum
  6. customchromatographed on silica gel using 0.5% methanol/CHCl3 as eluant

Sources & evidence

ORD record
ord-99e4930b68b44138a38487d31bf9dd9e
Source dataset
uspto-grants-1999_02
Patent number
US05869490

Reaction notes

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