4-{[(4-Chloro-1-guanidino-7-isoquinolinyl)sulphonyl]amino}tetrahydro-2H-pyran-4-carboxylic acid hydrochloride ##STR55## NaH (33.5 mg, 80% dispersion by wt in mineral oil, 1.12 mmol) was added in one portion to a stirred solution of guanidine hydrochloride (176 mg, 1.84 mmol) in DMSO (3.0 mL) under N2 and the mixture was heated at 50° C. for 15 min. Methyl 4-{[(1,4-dichloro-7-isoquinolinyl)sulphonyl]amino}tetrahydro-2H-pyran-4-carboxylate (187 mg, 0.446 mmol) was added in one portion and the mixture heated at 80° C. for 8 h. A second portion of guanidine (0.45 mmol) [prepared from guanidine hydrochloride and NaH] in DMSO (1.0 mL) was added and the mixture heated at 90° C. for an additional 4 h. The cooled mixture was poured into water (100 mL), extracted with EtOAc (3×50 mL) and the combined organic extracts were washed with brine, dried (Na2SO4). The solvents were evaporated in vacuo and the residue purified by column chromatography upon silica gel using CH2Cl2 -MeOH-0.880NH3 (95:5:0.5) as eluant, and then crystallised with EtOAc, to give to give methyl 4-{[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]amino}tetrahydro-2H-pyran-4-carboxylate (83 mg, 0.186 mmol) as a yellow solid.
