Thionyl Chloride → 1-Chloro-5-(1,4-diazepane-1-sulfonyl)isoquinoline

HRID 2118502Notes

Reaction equation

HRID 2118502 reaction equation
S(Cl)(Cl)=O.[Cl:5][C:6]1[C:15]2[CH:14]=[CH:13][CH:12]=[C:11]([S:16]([OH:19])(=[O:18])=O)[C:10]=2[CH:9]=[CH:8][N:7]=1.C(=O)([O-])O.[Na+].[NH:25]1[CH2:31][CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>ClCCl.O.CN(C)C=O>[Cl:5][C:6]1[C:15]2[CH:14]=[CH:13][CH:12]=[C:11]([S:16]([N:25]3[CH2:31][CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)(=[O:18])=[O:19])[C:10]=2[CH:9]=[CH:8][N:7]=1

Participants

8

Reactant 4

HCID 24386Thionyl ChlorideHCID 68163Hexahydro-1,4-diazepineHCID 516892Sodium BicarbonateHCID 137300201-Chloroisoquinoline-5-sulfonic acid

Product 1

HCID 223931531-Chloro-5-(1,4-diazepane-1-sulfonyl)isoquinolineYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

To 50 ml of thionyl chloride were added 5.85 g of 1-chloro-5-isoquinolinesulfonic acid as obtained in Example 1 and 0.5 ml of N,N-dimethylformamide. Then, the resulting mixture was refluxed while heating at 80° to 85° C. for 2 hours, followed by removal of the thionyl chloride and N,N-dimethylformamide under reduced pressure to obtain a residue. The residue was dissolved in a liquid consisting of 20 ml of water and 50 ml of dichloromethane, and the pH of the aqueous solution was adjusted to 6.0 with an aqueous sodium hydrogencarbonate saturated solution. Then, the dichloromethane layer was added to a 100 ml of a dichloromethane solution containing 6.0 g of homopiperazine for 20 minutes while cooling with ice, followed by stirring for 1 hour at a temperature of 15° C. to 20° C. The obtained reaction mixture was washed thrice with 50 ml of water, dried with anhydrous sodium sulfate and then distilled under reduced pressure to obtain oily residue. The thus obtained oily residue was subjected to purification by the silica gel column chromatography (Wacogel C-200, 150 g; solvent: a 5% methanol solution in chloroform), thereby to obtain 5.5 g of 1-(1-chloro-5-isoquinolinesulfonyl)homopiperazine, i.e., Compound (76), in a 84% yield. Analytical data on Compound (76) are given below.

Workup

  1. temperatureThen, the resulting mixture was refluxed
  2. temperaturewhile heating at 80° to 85° C. for 2 hours
  3. customfollowed by removal of the thionyl chloride and N,N-dimethylformamide under reduced pressure
  4. customto obtain a residue
  5. dissolutionThe residue was dissolved in a liquid
  6. temperaturewhile cooling with ice
  7. customThe obtained reaction mixture
  8. washwas washed thrice with 50 ml of water
  9. dry with materialdried with anhydrous sodium sulfate
  10. distillationdistilled under reduced pressure
  11. customto obtain oily residue
  12. customThe thus obtained oily residue was subjected to purification by the silica gel column chromatography (Wacogel C-200, 150 g

Sources & evidence

ORD record
ord-6eddf1b99d7543eba0ae3e82068030fe
Source dataset
uspto-grants-1987_07
Patent number
US04678783

Reaction notes

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