Water → HCID 178450692, compound

HRID 2289698Notes

Reaction equation

FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([S:19]([NH:22][C:23]3[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=3)[C:26]([OH:28])=[O:27])(=[O:21])=[O:20])=[CH:16][CH:17]=2)[C:12]([NH:32][C:33]([NH2:35])=[NH:34])=[N:11][CH:10]=1.[H-].[Na+].ClC1[C:48]2[C:43](=[CH:44]C=C(S(NC3C=C(C=CC=3)C(OC(C)(C)C)=O)(=O)=O)C=2)[C:42](Cl)=CN=1.O>CS(C)=O>[Cl:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([S:19]([NH:22][C:23]3[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=3)[C:26]([O:28][C:43]([CH3:48])([CH3:44])[CH3:42])=[O:27])(=[O:20])=[O:21])=[CH:16][CH:17]=2)[C:12]([NH:32][C:33]([NH2:35])=[NH:34])=[N:11][CH:10]=1

Participants

Conditions

Temperature: 60 °C

Procedure

3-{[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]amino}benzoic acid trifluoroacetate ##STR11## Guanidine hydrochloride (140 mg, 1.47 mmol) was added in one portion to a suspension of NaH (44 mg, 80% dispersion by wt in mineral oil, 1.47 mmol) in DMSO (4.0 mL) and the mixture was heated at 60° C. under N2 for 30 min. A solution of tert-butyl 3-{[(1,4-dichloro-7-isoquinolinyl)-sulphonyl]amino}benzoate (280 mg, 0.59 mmol) in DMSO (2.0 mL) was added and the mixture heated at 90° C. for 18 h. The cooled mixture was poured into water (50 mL), extracted with EtOAc (×3) and the combined organic phase was then evaporated in vacuo. The residue was purified by column chromatography upon silica gel using CH2Cl2 -MeOH-0.880NH3 (97:3:0.3 to 95:5:0.5) as eluant to give tert-butyl 3-{[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]amino}benzoate (64 mg, 0.13 mmol) as a tan solid.

Workup

temperaturethe mixture heated at 90° C. for 18 h
extractionextracted with EtOAc (×3)
customthe combined organic phase was then evaporated in vacuo
customThe residue was purified by column chromatography upon silica gel

Sources & evidence

ORD record: ord-41cf2bcc97904d0489a4ac8dc25d906a
Source dataset: uspto-grants-2000_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06093731

Reaction notes

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