Sodium hydride → HCID 178451140, compound

HRID 2289756Notes

Reaction equation

HRID 2289756 reaction equation
Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([S:13]([NH:16][C@H:17]3[CH2:22][CH2:21][CH2:20][CH2:19][C@H:18]3[C:23]([OH:25])=[O:24])(=[O:15])=[O:14])=[CH:10][CH:11]=2)[C:6]([NH:26][C:27]([NH2:29])=[NH:28])=[N:5][CH:4]=1.[H-].[Na+].ClC1[C:42]2[C:37](=[CH:38]C=C(S(N[C@H]3CCCC[C@H]3C(OC(C)(C)C)=O)(=O)=O)C=2)[C:36](Cl)=CN=1>COCCOC>[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([S:13]([NH:16][C@H:17]3[CH2:22][CH2:21][CH2:20][CH2:19][C@H:18]3[C:23]([O:25][C:37]([CH3:42])([CH3:38])[CH3:36])=[O:24])(=[O:14])=[O:15])=[CH:10][CH:11]=2)[C:6]([NH:26][C:27]([NH2:29])=[NH:28])=[N:5][CH:4]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86590049HCID 86590049, compoundHCID 178479408HCID 178479408, compound

Product 1

HCID 178451140HCID 178451140, compoundYield 17.6%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
60 °C

Procedure

(±)-cis-2-{[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]amino}cyclohexanecarboxylic acid hydrochloride ##STR56## Guanidine hydrochloride (325 mg, 3.4 mmol) was added in one portion to a stirred suspension of NaH (89 mg, 80% dispersion by wt in mineral oil, 2.97 mmol) in DME (5 mL) and the mixture was heated at 60° C. under N2 for 30 min. A solution of t-butyl (±)-cis-2-{[(1,4-dichloro-7-isoquinolinyl)sulphonyl]amino}cyclohexanecarboxylate (391 mg, 0.85 mmol) in DME (5 mL) was added and the mixture heated at 90° C. for 6 h. The solvents were evaporated in vacuo, the residue was dissolved with EtOAc, washed with aqueous NH4Cl, dried (MgSO4) and evaporated in vacuo. The residue was purified by column chromatography upon silica gel using using toluene-i-PrOH-0.880NH3 (100:0:0 to 90:10:0.05) as eluant to give t-butyl (±)-cis-2-{[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]amino}cyclohexanecarboxylate (75 mg, 0.15 mmol) as a white solid.

Workup

  1. temperaturethe mixture heated at 90° C. for 6 h
  2. customThe solvents were evaporated in vacuo
  3. dissolutionthe residue was dissolved with EtOAc
  4. washwashed with aqueous NH4Cl
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography upon silica gel using

Sources & evidence

ORD record
ord-191e10e301294ea7b007e9fbf88b3148
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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