Sodium hydride → HCID 178451243, compound

HRID 2289725Notes

Reaction equation

HRID 2289725 reaction equation
Cl.Cl.[Cl:3][C:4]1[C:13]2[C:8](=[CH:9][C:10]([S:14]([N:17]([CH2:22][C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)[CH2:18][C:19]([OH:21])=[O:20])(=[O:16])=[O:15])=[CH:11][CH:12]=2)[C:7]([NH:29][C:30]([NH2:32])=[NH:31])=[N:6][CH:5]=1.[H-].[Na+].[C:35](OC(=O)CN(S(C1C=C2C(C(Cl)=CN=C2Cl)=CC=1)(=O)=O)CC1C=NC=CC=1)([CH3:38])([CH3:37])[CH3:36]>COCCOC>[C:35]([O:20][C:19](=[O:21])[CH2:18][N:17]([S:14]([C:10]1[CH:9]=[C:8]2[C:13]([C:4]([Cl:3])=[CH:5][N:6]=[C:7]2[NH:29][C:30]([NH2:32])=[NH:31])=[CH:12][CH:11]=1)(=[O:15])=[O:16])[CH2:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1)([CH3:38])([CH3:37])[CH3:36]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 18698268HCID 18698268, compoundHCID 178478802HCID 178478802, compound

Product 1

HCID 178451243HCID 178451243, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
60 °C

Procedure

N-[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(3-pyridylmethyl)glycine dihydrochloride ##STR26## Guanidine hydrochloride (317 mg, 3.32 mmol was added in one portion to a stirred suspension of NaH (62.3 mg, 80% dispersion by wt in mineral oil, 2.08 mmol) in DME (10 mL) and the mixture was heated at 60° C. under N2 for 30 min. A solution of N-[(1,4-dichloro-7-isoquinolinyl)sulphonyl]-N-(3-pyridylmethyl)glycine t-butyl ester (400 mg, 0.83 mmol) in DME (10 mL) was added and the mixture heated at 80° C. for 4 h. The solvents were evaporated in vacuo, the residue was dissolved with EtOAc (200 mL), and washed with aqueous NH4Cl (200 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by column chromatography upon silica gel using (i) pentane-EtOAc (70:30 to 50:50) and then (ii) CH2Cl2 -MeOH-0.880NH3 (95:5:0.5 to 90:101) as eluant to give N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(3-pyridylmethyl)glycine t-butyl ester (104 mg, 0.21 mmol) as a pale yellow solid.

Workup

  1. temperaturethe mixture heated at 80° C. for 4 h
  2. customThe solvents were evaporated in vacuo
  3. dissolutionthe residue was dissolved with EtOAc (200 mL)
  4. washwashed with aqueous NH4Cl (200 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography upon silica gel using (i) pentane-EtOAc (70:30 to 50:50)

Sources & evidence

ORD record
ord-09306ad77ba242068be145932850a004
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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