Water → HCID 178451235, compound

HRID 2289712Notes

Reaction equation

HRID 2289712 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([S:19]([N:22]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:23][C:24]([OH:26])=[O:25])(=[O:21])=[O:20])=[CH:16][CH:17]=2)[C:12]([NH:34][C:35]([NH2:37])=[NH:36])=[N:11][CH:10]=1.[H-].[Na+].[C:40](OC(=O)CN(S(C1C=C2C(C(Cl)=CN=C2Cl)=CC=1)(=O)=O)CC1C=CC=CC=1)([CH3:43])([CH3:42])[CH3:41].O>COCCOC>[C:40]([O:25][C:24](=[O:26])[CH2:23][N:22]([S:19]([C:15]1[CH:14]=[C:13]2[C:18]([C:9]([Cl:8])=[CH:10][N:11]=[C:12]2[NH:34][C:35]([NH2:37])=[NH:36])=[CH:17][CH:16]=1)(=[O:20])=[O:21])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([CH3:43])([CH3:42])[CH3:41]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 16658744HCID 16658744, compoundHCID 178512671HCID 178512671, compound

Product 1

HCID 178451235HCID 178451235, compoundYield 72.8%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
60 °C

Procedure

N-[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-benzylglycine trifluoroacetate ##STR19## Guanidine hydrochloride (180 mg, 1.88 mmol) was added in one portion to a suspension of NaH (45 mg, 80% dispersion by wt in mineral oil, 1.5 mmol) in DME (11 mL) and the mixture was heated at 60° C. under N2 for 30 min. N-[(1,4-Dichloro-7-isoquinolinyl)sulphonyl]-N-benzylglycine t-butyl ester (225 mg, 0.467 mmol) was added and the mixture heated at 90° C. for 18 h. The cooled mixture was poured into water, extracted with EtOAc (×3) and the combined organic phase was then washed with water, dried (Na2SO4) and evaporated in vacuo. The residue was purified by column chromatography upon silica gel using CH2Cl2 -MeOH-0.880NH3 (97:3:0.3) as eluant to give N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-benzylglycine t-butyl ester (172 mg, 0.34 mmol) as a yellow foam.

Workup

  1. temperaturethe mixture heated at 90° C. for 18 h
  2. extractionextracted with EtOAc (×3)
  3. washthe combined organic phase was then washed with water
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo
  6. customThe residue was purified by column chromatography upon silica gel

Sources & evidence

ORD record
ord-3d58f43333da46ffb92b67b7adedf04b
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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