Water → HCID 178491118, compound

HRID 2289721Notes

Reaction equation

HRID 2289721 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[CH2:16][C:17]([OH:19])=[O:18])(=[O:14])=[O:13])=[CH:9][CH:10]=2)[C:5]([NH:29][C:30]([NH2:32])=[NH:31])=[N:4][CH:3]=1.[H-].[Na+].[C:35]([O:39][C:40](=O)[CH2:41]N(S(C1C=C2C(C(Cl)=CN=C2Cl)=CC=1)(=O)=O)CC1C=CC(OC)=CC=1)([CH3:38])([CH3:37])[CH3:36].O>COCCOC>[O:39]([CH:35]([CH3:37])[CH3:38])[CH:40]([CH3:41])[CH3:2].[C:35]([O:18][C:17](=[O:19])[CH2:16][N:15]([S:12]([C:8]1[CH:7]=[C:6]2[C:11]([C:2]([Cl:1])=[CH:3][N:4]=[C:5]2[NH:29][C:30]([NH2:32])=[NH:31])=[CH:10][CH:9]=1)(=[O:13])=[O:14])[CH2:20][C:21]1[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=1)([CH3:38])([CH3:37])[CH3:36]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 18698353HCID 18698353, compoundHCID 178491121HCID 178491121, compound

Product 2

HCID 7914Diisopropyl EtherHCID 178491118HCID 178491118, compoundYield 96.8%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
60 °C

Procedure

N-[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(4-methoxybenzyl)glycine ##STR24## Guanidine hydrochloride (118 mg, 1.24 mmol) was added in one portion to a stirred suspension of NaH (23 mg, 80% dispersion by wt in mineral oil, 0.78 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-(4-methoxybenzyl)glycine t-butyl ester (155 mg, 0.31 mmol) was added and the mixture heated at 90° C. for 1 h. The cooled mixture was poured into water and extracted with EtOAc (×3). The combined organic extracts were then washed with water, brine, dried (Na2SO4) and evaporated in vacuo. The residue was purified by column chromatography upon silica gel using hexane-EtOAc (80:20), and then CH2Cl2 -MeOH-0.880NH3 (95:5:0.5 to 90:10:1) as eluant to give a yellow gum. Trituration with i-Pr2O gave N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(4-methoxybenzyl)glycine t-butyl ester (80 mg, 0.15 mmol) as a sticky yellow solid. A small sample (10-15 mg) was dissolved in EtOAc, a solution of HCl in Et2O was added and the solvents were evaporated in vacuo, to give N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(4-methoxybenzyl)glycine t-butyl ester hydrochloride (18 mg) as a solid. (All characterisation data is for the HCl salt).

Workup

  1. temperaturethe mixture heated at 90° C. for 1 h
  2. extractionextracted with EtOAc (×3)
  3. washThe combined organic extracts were then washed with water, brine
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo
  6. customThe residue was purified by column chromatography upon silica gel
  7. custom880NH3 (95:5:0.5 to 90:10:1) as eluant to give a yellow gum

Sources & evidence

ORD record
ord-bc97715a058a4562a834804328a12b25
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

Loading…