Hydrochloric Acid → HCID 178483754, compound

HRID 2289791Notes

Reaction equation

HRID 2289791 reaction equation
[ClH:1].Cl.C([CH:5]1[CH2:33][CH2:32][CH2:31][C:6]1([C:34]([OH:36])=[O:35])[N:7]([S:13]([C:16]1[CH:25]=[C:24]2[C:19]([C:20]([Br:30])=[CH:21][N:22]=[C:23]2[NH:26][C:27]([NH2:29])=[NH:28])=[CH:18][CH:17]=1)(=[O:15])=[O:14])[CH2:8][CH2:9][N:10]([CH3:12])[CH3:11])C.[OH-].[Na+].Cl>CCO>[ClH:1].[ClH:1].[Br:30][C:20]1[C:19]2[C:24](=[CH:25][C:16]([S:13]([N:7]([CH2:8][CH2:9][N:10]([CH3:12])[CH3:11])[C:6]3([C:34]([OH:36])=[O:35])[CH2:31][CH2:32][CH2:33][CH2:5]3)(=[O:14])=[O:15])=[CH:17][CH:18]=2)[C:23]([NH:26][C:27]([NH2:29])=[NH:28])=[N:22][CH:21]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 178435657HCID 178435657, compound

Product 1

HCID 178483754HCID 178483754, compoundYield 31.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

Ethyl N-[(4-Bromo-1-guanidino-7-isoquinolinyl)sulphonyl]-N-[2-(dimethylamino)ethyl]cycloleucine dihydrochloride (95 mg, 0.17 mmol) in EtOH (3 ml) was treated with NaOH (4N, 8 ml) and the solution stirred at 60° C. for 5 h and allowed to stand for 60 h at room temperature. The reaction mixture was acidified using 2N HCl, concentrated in vacuo and the residue azeotroped with i-PrOH to give an off-white solid. This was extracted into MeOH, the solution evaporated in vacuo and the residue purified by column chromatography upon silica gel using CH2Cl2 -MeOH-0.880 NH3 (80:20:5) as eluant. The product was suspended in EtOAc, treated with ethereal HCl, the mixture evaporated in vacuo and the product triturated with EtOAc to afford N-({4-bromo-1-guanidino-7-isoquinolinyl}sulphonyl)-N-[2-(dimethylamino)ethyl]cycloleucine dihydrochloride (15 mg, 0.027 mmol) as a pale yellow solid.

Workup

  1. waitto stand for 60 h at room temperature
  2. concentrationconcentrated in vacuo
  3. customthe residue azeotroped with i-PrOH
  4. customto give an off-white solid
  5. extractionThis was extracted into MeOH
  6. customthe solution evaporated in vacuo
  7. customthe residue purified by column chromatography upon silica gel
  8. additiontreated with ethereal HCl
  9. customthe mixture evaporated in vacuo
  10. customthe product triturated with EtOAc

Sources & evidence

ORD record
ord-01d9ac19e28242bca5ff7f478da61695
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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