Water → HCID 178499191, compound

HRID 2289753Notes

Reaction equation

HRID 2289753 reaction equation
Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([S:13]([NH:16][C:17]3([C:23]([OH:25])=[O:24])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)(=[O:15])=[O:14])=[CH:10][CH:11]=2)[C:6]([NH:26][C:27]([NH2:29])=[NH:28])=[N:5][CH:4]=1.Cl.N[C:32](N)=N.ClC1C2C(=CC=C(S(NC3(C(OC)=O)CCCCC3)(=O)=O)C=2)C(Cl)=CN=1.O>CS(C)=O>[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([S:13]([NH:16][C:17]3([C:23]([O:25][CH3:32])=[O:24])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)(=[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

6

Reactant 4

HCID 962WaterHCID 5742Guanidine HydrochlorideHCID 16658027Methyl 1-{[(1,4-dichloro-7-isoquinolinyl)sulphonyl]amino}-cyclohexanecarboxylateHCID 178479403HCID 178479403, compound

Product 1

HCID 178499191HCID 178499191, compoundYield 5.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

1-{[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]amino}cyclohexanecarboxylic acid hydrochloride ##STR54## NaH (22.3 mg, 80% dispersion by wt in mineral oil, 0.743 mmol) was added in one portion to a stirred solution of guanidine hydrochloride (117 mg, 1.98 mmol) in DMSO (5 mL) and the mixture was heated at 50-70° C. under N2 for 25 min. Methyl 1-{[(1,4-dichloro-7-isoquinolinyl)sulphonyl]amino}-cyclohexanecarboxylate (124 mg, 0.30 mmol) was added in one portion and the mixture heated at 80° C. for 8 h. The cooled mixture was poured into water (50 mL), extracted with EtOAc (2×50 mL) and the combined organic extracts were washed with water, brine, dried (MgSO4) and evaporated in vacuo. The residue was crystallised from a minimum of hot EtOAc to give methyl 1-{[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]amino}cyclohexanecarboxylate (12 mg, 0.043 mmol) as yellow solid. Evaporation of the mother liquors and trituration of the residue with Et2O gave a second crop (7 mg).

Workup

  1. temperaturethe mixture heated at 80° C. for 8 h
  2. extractionextracted with EtOAc (2×50 mL)
  3. washthe combined organic extracts were washed with water, brine
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo
  6. customThe residue was crystallised from a minimum of hot EtOAc

Sources & evidence

ORD record
ord-93568fb32c9d426faa1cc4ef8da2bb0f
Source dataset
uspto-grants-2000_07
Patent number
US06093731

Reaction notes

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