Hydrochloric Acid → HCID 18354551, compound

HRID 429150Notes

Reaction equation

HRID 429150 reaction equation
[Cl:1]C(OC(Cl)=O)C.[CH3:8][O:9][C:10]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]2[C:11]=1[CH2:12][CH2:13][N:14]([S:22]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[C:27]([N:33]3[CH2:38][CH2:37][N:36](C)[CH2:35][CH2:34]3)[CH:26]=1)(=[O:24])=[O:23])[CH2:15]2.C(N(C(C)C)CC)(C)C.Cl>ClCCCl.CC(C)=O.ClCCl>[ClH:1].[CH3:8][O:9][C:10]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]2[C:11]=1[CH2:12][CH2:13][N:14]([S:22]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[C:27]([N:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)[CH:26]=1)(=[O:24])=[O:23])[CH2:15]2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 17940230HCID 17940230, compound

Product 1

HCID 18354551HCID 18354551, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 21584124Propan-2-one--dichloromethane (1/1)Solvent

Procedure

A solution of 1-chloroethylchloroformate (0.12 ml;1.11 mmol) and 5,8-dimethoxy-2-[4-methoxy-3-(4-methyl-1-piperazinyl)benzenesulfonyl]-1,2,3,4-tetrahydroisoquinoline (E21) (111 mg;0.223 mmol) in 1,2-dichloroethane (3 ml) was refluxed for 0.75 h, cooled, diluted with diisopropylethylamine (0.19 ml;1.11 mmol) and refluxed for a further 2.5 hrs. The solution was concentrated to a residue which was re-dissolved in methanol, refluxed for 1 hr and then stirred at room temperature for 24 h. The mixture was concentrated, and the residue partitioned between ethyl acetate and aqueous sodium bicarbonate solution. The organic layer was dried, concentrated to a residue and purified by column chromatography on silica gel using a methanol/dichloromethane solvent gradient. The title compound was prepared by dissolving the pure free base material from chromatography in acetone/dichloromethane and acidifying with 1M ethereal HCl (53 mg, 49%). MH+456/458.

Workup

  1. temperaturecooled
  2. temperaturerefluxed for a further 2.5 hrs
  3. concentrationThe solution was concentrated to a residue which
  4. dissolutionwas re-dissolved in methanol
  5. temperaturerefluxed for 1 hr
  6. concentrationThe mixture was concentrated
  7. customthe residue partitioned between ethyl acetate and aqueous sodium bicarbonate solution
  8. customThe organic layer was dried
  9. concentrationconcentrated to a residue
  10. custompurified by column chromatography on silica gel using a methanol/dichloromethane solvent gradient

Sources & evidence

ORD record
ord-33e841f47b0c4439979089be8e1da74a
Source dataset
uspto-grants-2001_11
Patent number
US06316450B1

Reaction notes

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