Sodium hydride → HCID 178451176, compound

HRID 2289744Notes

Reaction equation

Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([S:13]([N:16]3[CH2:23][CH2:22][CH2:21][C@@H:17]3[C:18]([OH:20])=[O:19])(=[O:15])=[O:14])=[CH:10][CH:11]=2)[C:6]([NH:24][C:25]([NH2:27])=[NH:26])=[N:5][CH:4]=1.[H-].[Na+].[C:30](OC(=O)[C@H]1CCCN1NS(C1C=C2C(C(Cl)=CN=C2Cl)=CC=1)(=O)=O)([CH3:33])([CH3:32])[CH3:31]>COCCOC.CCOC(C)=O>[C:30]([O:19][C:18](=[O:20])[C@H:17]1[CH2:21][CH2:22][CH2:23][N:16]1[S:13]([C:9]1[CH:8]=[C:7]2[C:12]([C:3]([Cl:2])=[CH:4][N:5]=[C:6]2[NH:24][C:25]([NH2:27])=[NH:26])=[CH:11][CH:10]=1)(=[O:15])=[O:14])([CH3:33])([CH3:32])[CH3:31]

Participants

Conditions

Temperature: 60 °C

Procedure

N-[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-D-proline hydrochloride ##STR41## Guanidine hydrochloride (220 mg, 2.3 mmol) was added in one portion to a stirred suspension of NaH (55 mg, 80% dispersion by wt in mineral oil, 1.83 mmol) in DME (8 mL) and the mixture was heated at 60° C. under N2 for 30 min. 1-{[(1,4-Dichloro-7-isoquinolinyl)sulphonyl]amino}-D-proline t-butyl ester (250 mg, 0.58 mmol) was added and the mixture heated at reflux for 5 h. The cooled mixture was diluted with EtOAc, washed with water, brine, dried (MgSO4) and the solvents evaporated in vacuo. The residue was purified by column chromatography upon silica gel using CH2Cl2 -MeOH-0.880NH3 (97:3:0.3) as eluant to give N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-D-proline t-butyl ester (200 mg, 0.44 mmol) as a yellow solid.

Workup

temperaturethe mixture heated
temperatureat reflux for 5 h
washwashed with water, brine
dry with materialdried (MgSO4)
customthe solvents evaporated in vacuo
customThe residue was purified by column chromatography upon silica gel

Sources & evidence

ORD record: ord-e90b28c772e740c19cb46c9bc71e6d71
Source dataset: uspto-grants-2000_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06093731

Reaction notes

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