Water → HCID 178501486, compound

HRID 2289737Notes

Reaction equation

Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([S:13]([NH:16][C@@H:17]([C:19]([OH:21])=[O:20])[CH3:18])(=[O:15])=[O:14])=[CH:10][CH:11]=2)[C:6]([NH:22][C:23]([NH2:25])=[NH:24])=[N:5][CH:4]=1.Cl.N[C:28](N)=N.O>CS(C)=O>[CH3:28][O:20][C:19](=[O:21])[C@@H:17]([CH3:18])[NH:16][S:13]([C:9]1[CH:8]=[C:7]2[C:12]([C:3]([Cl:2])=[CH:4][N:5]=[C:6]2[NH:22][C:23]([NH2:25])=[NH:24])=[CH:11][CH:10]=1)(=[O:14])=[O:15]

Participants

Conditions

Temperature: 60 °C

Procedure

N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-D-alanine hydrochloride ##STR33## NaH (35 mg, 80% dispersion by wt in mineral oil, 1.17 mmol) was added in one portion to a stirred solution of guanidine hydrochloride (179 mg, 1.87 mmol) in DMSO (5 mL) and the mixture was heated at 60° C. under N2 for 45 min. 1-{[(1,4-Dichloro-7-isoquinolinyl)sulphonyl]amino}-D-alanine methyl ester (170 mg, 0.47 mmol) was added and the mixture heated at 90° C. for 4 h. The cooled mixture was poured into water and extracted with EtOAc (3×30 mL). The combined organic extracts were dried (MgSO4) and the solvents evaporated in vacuo. The residue was purified by column chromatography upon silica gel using pentane-EtOAc (66:33 to 0:100) as eluant to give N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-D-alanine methyl ester (22 mg, 0.057 mmol) as a yellow foam/oil.

Workup

temperaturethe mixture heated at 90° C. for 4 h
extractionextracted with EtOAc (3×30 mL)
dry with materialThe combined organic extracts were dried (MgSO4)
customthe solvents evaporated in vacuo
customThe residue was purified by column chromatography upon silica gel

Sources & evidence

ORD record: ord-58392633043e4ad88d2fdd2d33ee2376
Source dataset: uspto-grants-2000_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06093731

Reaction notes

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