Triethylamine → 2-[4-[4-(6-chloro-2-pyrazinyl)-1-piperazinyl]butyl]-3a,4,7,7a-tetrahydro-4,7-ethano-1,2-benzisothiazol-3(2H)-one 1,1-dioxide,hydrochloride

HRID 569578Notes

Reaction equation

HRID 569578 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10](=[O:11])[CH:9]2[CH:12]3[CH2:17][CH2:16][CH:15]([CH:8]2[S:7]1(=[O:19])=[O:18])[CH:14]=[CH:13]3.C(N(CC)CC)C.Cl.[Cl:28][C:29]1[N:34]=[C:33]([N:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH:32]=[N:31][CH:30]=1>CN(C)C=O>[ClH:28].[Cl:28][C:29]1[N:34]=[C:33]([N:35]2[CH2:36][CH2:37][N:38]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]3[C:10](=[O:11])[CH:9]4[CH:12]5[CH2:17][CH2:16][CH:15]([CH:8]4[S:7]3(=[O:19])=[O:18])[CH:14]=[CH:13]5)[CH2:39][CH2:40]2)[CH:32]=[N:31][CH:30]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 198421MK-212 hydrochlorideHCID 201476643a,4,7,7a-Tetrahydro-2-[4-bromobutyl]-4,7-ethano-1,2-benzisothiazol-3(2H)-one 1,1-dioxide

Product 1

HCID 201476682-[4-[4-(6-chloro-2-pyrazinyl)-1-piperazinyl]butyl]-3a,4,7,7a-tetrahydro-4,7-ethano-1,2-benzisothiazol-3(2H)-one 1,1-dioxide,hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1.0 g (2.9 mmol) of 3a,4,7,7a-tetrahydro-2-(4-bromobutyl)-4,7-ethano-1,2-benzisothiazol-3(2H)-one 1,1-dioxide in 25 ml of anhydrous dimethylformamide is treated with 1.6 g (16 mmol) of triethylamine and 866 mg (3.2 mmol) of 1-(6-chloro-2-pyrazinyl)piperazine, monohydrochloride salt. The mixture is maintained at room temperature with stirring for 15 hours and then is partitioned between water and methylene chloride. The methylene chloride extracts are combined, dried over MgSO4, filtered and rotoevaporated to give crude free base. Preparative HPLC (silica gel; ethyl acetate: methylene chloride (9:1)) followed by evaporation of the appropriate fractions, treatment with ethanolic hydrochloric acid and recrystallization from methanol gives the title compound: mp. 263°-267° C.

Workup

  1. customis partitioned between water and methylene chloride
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customto give crude free base
  5. customPreparative HPLC (silica gel; ethyl acetate: methylene chloride (9:1)) followed by evaporation of the appropriate fractions, treatment with ethanolic hydrochloric acid and recrystallization from methanol

Sources & evidence

ORD record
ord-9abfd88af25c40cf9e32d5b68c00eec1
Source dataset
uspto-grants-1988_03
Patent number
US04732984

Reaction notes

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