Water → HCID 178490339, compound

HRID 2289717Notes

Reaction equation

HRID 2289717 reaction equation
[Cl:1]C1C2C(=CC(S(N(CC3C=CC=C(OC)C=3)CC(O)=O)(=O)=O)=CC=2)C([NH:29][C:30]([NH2:32])=[NH:31])=NC=1.[H-].[Na+].[C:35]([O:39][C:40](=[O:67])[CH2:41][N:42]([S:52]([C:55]1[CH:64]=[C:63]2[C:58]([C:59]([Cl:66])=[CH:60][N:61]=[C:62]2Cl)=[CH:57][CH:56]=1)(=[O:54])=[O:53])[CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[C:46]([O:50][CH3:51])[CH:45]=1)([CH3:38])([CH3:37])[CH3:36].O>COCCOC>[ClH:1].[C:35]([O:39][C:40](=[O:67])[CH2:41][N:42]([S:52]([C:55]1[CH:64]=[C:63]2[C:58]([C:59]([Cl:66])=[CH:60][N:61]=[C:62]2[NH:31][C:30]([NH2:32])=[NH:29])=[CH:57][CH:56]=1)(=[O:53])=[O:54])[CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[C:46]([O:50][CH3:51])[CH:45]=1)([CH3:36])([CH3:37])[CH3:38]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 18698239HCID 18698239, compoundHCID 178490340HCID 178490340, compound

Product 1

HCID 178490339HCID 178490339, compoundYield 53.8%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
60 °C

Procedure

N-[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(3-methoxybenzyl)glycine ##STR22## Guanidine hydrochloride (149 mg, 1.55 mmol) was added in one portion to a suspension of NaH (35 mg, 80% dispersion by wt in mineral oil, 1.16 mmol) in DME (10 mL) and the mixture was heated at 60° C. under N2 for 30 min. N-[(1,4-Dichloro-7-isoquinolinyl)sulphonyl]-N-(3-methoxybenzyl)glycine t-butyl ester (200 mg, 0.39 mmol) was added and the mixture heated at 90° C. for 2 h. The cooled mixture was poured into water, extracted with EtOAc (×3), and the combined organic extracts were washed with brine, dried (Na2SO4) and evaporated in vacuo. The residue was dissolved in Et2O-EtOAc and a solution of HCl in Et2O (0.5 M) was added to give a precipitate. The solid was collected by filtration, triturated with EtOAc and then dried to give N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(3-methoxybenzyl)glycine t-butyl ester hydrochloride (124 mg, 0.21 mmol) as a white solid.

Workup

  1. temperaturethe mixture heated at 90° C. for 2 h
  2. extractionextracted with EtOAc (×3)
  3. washthe combined organic extracts were washed with brine
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo
  6. dissolutionThe residue was dissolved in Et2O-EtOAc
  7. additiona solution of HCl in Et2O (0.5 M) was added
  8. customto give a precipitate
  9. filtrationThe solid was collected by filtration
  10. customtriturated with EtOAc
  11. customdried

Sources & evidence

ORD record
ord-1302e4562f6e49d087473d1b2f1fab0f
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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