Sodium Carbonate → 1-(1-Chloro-5-isoquinolinesulfonylaminoethyl)-4-[3-(phenoxy) propyl]piperazine

HRID 1728399Notes

Reaction equation

HRID 1728399 reaction equation
Cl[C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([S:12]([OH:15])(=[O:14])=O)[C:6]=2[CH:5]=[CH:4][N:3]=1.S(Cl)([Cl:18])=O.C(=O)([O-])[O-].[Na+].[Na+].[NH2:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][CH2:37][O:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:31][CH2:30]1>C(N(CC)CC)C.ClCCl.CN(C)C=O>[Cl:18][CH:28]([N:29]1[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][CH2:37][O:38][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH2:31][CH2:30]1)[CH2:27][NH:26][S:12]([C:7]1[C:6]2[CH:5]=[CH:4][N:3]=[CH:2][C:11]=2[CH:10]=[CH:9][CH:8]=1)(=[O:14])=[O:15]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 24386Thionyl ChlorideHCID 137300201-Chloroisoquinoline-5-sulfonic acidHCID 190180451-(2-Aminoethyl)-4-[3-(phenoxy)propyl]piperazine

Product 1

HCID 678297351-(1-Chloro-5-isoquinolinesulfonylaminoethyl)-4-[3-(phenoxy) propyl]piperazineYield 69%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

To 14.2 g of 1-chloro-5-isoquinolinesulfonic acid were added 142 ml of thionyl chloride and 1 . 42 ml of dimethylformamide. The resultant mixture was heated under reflux for 3 hours and the thionyl chloride was removed by distillation under reduced pressure to obtain a residue. The thus obtained residue was dissolved in 100 ml of ice water and adjusted to a pH of 6 with a saturated aqueous sodium carbonate solution, followed by extraction with 100 ml of dichloromethane to obtain a dichloromethane phase. The dichloromethane phase was dropwise added to 100 ml of a dichloromethane solution containing 15.4 g of 1-(2-aminoethyl)-4-[3-(phenoxy)propyl]piperazine and 6.5 g of triethylamine over 30 minutes while cooling with ice. The resultant mixture was stirred at a temperature of 15° C. to 20° C. for 2 hours to carry out a reaction. After completion of the reaction, the reaction mixture was washed with 200 ml of water and dried over anhydrous magnesium sulfate. Then, solvent removal was conducted by distillation under reduced pressure to thereby obtain a residue. The thus obtained residue was subjected to purification by means of a column for chromatography packed with 250 g of silica gel (Wakogel C-200, manufactured by Wako Pure Chemical Industries, Ltd., Japan) using a mixed solvent of methanol and chloroform (2% methanol) as an eluent, to thereby obtain 19.6 g of 1 -(1-chloro-5-isoquinolinesulfonylaminoethyl)-4-[3-(phenoxy) propyl]piperazine (yield: 69%).

Workup

  1. temperatureunder reflux for 3 hours
  2. customthe thionyl chloride was removed by distillation under reduced pressure
  3. customto obtain a residue
  4. extractionfollowed by extraction with 100 ml of dichloromethane
  5. customto obtain a dichloromethane phase
  6. temperaturewhile cooling with ice
  7. customa reaction
  8. customAfter completion of the reaction
  9. washthe reaction mixture was washed with 200 ml of water
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThen, solvent removal
  12. distillationwas conducted by distillation under reduced pressure
  13. customto thereby obtain a residue
  14. customThe thus obtained residue was subjected to purification by means of a column for chromatography

Sources & evidence

ORD record
ord-5d6877dba26449438da3cf55000a3d3f
Source dataset
uspto-grants-1994_07
Patent number
US05326870

Reaction notes

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