Sodium hydride → HCID 178424263, compound

HRID 2289714Notes

Reaction equation

HRID 2289714 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][C:29]=3[CH3:34])[CH2:23][C:24]([OH:26])=[O:25])(=[O:21])=[O:20])=[CH:16][CH:17]=2)[C:12]([NH:35][C:36]([NH2:38])=[NH:37])=[N:11][CH:10]=1.[H-].[Na+].[C:41](OC(=O)CN(S(C1C=C2C(C(Cl)=CN=C2Cl)=CC=1)(=O)=O)CC1C=CC=CC=1C)([CH3:44])([CH3:43])[CH3:42]>COCCOC.CCOC(C)=O>[C:41]([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:35][C:36]([NH2:38])=[NH:37])=[CH:17][CH:16]=1)(=[O:20])=[O:21])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[CH3:34])([CH3:44])([CH3:43])[CH3:42]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 18698336HCID 18698336, compoundHCID 178424264HCID 178424264, compound

Product 1

HCID 178424263HCID 178424263, compoundYield 44.4%

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

N-[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(2-methylbenzyl)glycine trifluoroacetate ##STR20## Guanidine hydrochloride (120 mg, 1.26 mmol) was added in one portion to a suspension of NaH (32 mg, 80% dispersion by wt in mineral oil, 1.06 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-(2-methylbenzyl)glycine t-butyl ester (200 mg, 0.405 mmol) was added and the mixture heated at 90° C. for 2 h. The cooled mixture was diluted with EtOAc, washed with water, brine, dried (Na2SO4) and evaporated in vacuo. The residue was purified by column chromatography upon silica gel using pentane-CH2Cl2 (50:50), then CH2Cl2, and finally CH2Cl2 -MeOH-0.880NH3 (95:5:0.5) as eluant to give N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(2-methylbenzyl)glycine t-butyl ester (94 mg, 0.18 mmol) as an off-white solid.

Workup

  1. temperaturethe mixture heated at 90° C. for 2 h
  2. washwashed with water, brine
  3. dry with materialdried (Na2SO4)
  4. customevaporated in vacuo
  5. customThe residue was purified by column chromatography upon silica gel

Sources & evidence

ORD record
ord-a18857348fa540b096af404d459b302f
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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