Potassium Hydroxide → HCID 178440237, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-ethyl-6,7-dimethoxyisoquinolin-3-ol RBO 35142 (117 mg, 473 μmol) in toluene (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.52 mL, 1.04 mmol) at RT followed by 3-(chloromethyl)-7-methoxyquinoline hydrochloride MDE 32012 (124 mg, 508 μmol) and the mixture was stirred at 150° C. for 2 h under microwave irradiation. After cooling to RT, the mixture was diluted with CH2Cl2 (50 mL) and H2O (10 mL). The organic phase was isolated and the aqueous phase was further extracted with CH2Cl2 (50 mL). The combined organic phase was washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5) gave 26 mg of 6,7-dimethoxy-4-((7-methoxyquinolin-3-yl)methyl)-1-propylisoquinolin-3-ol. This free base was dissolved in MeOH (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.09 M HCl solution in MeOH (2.0 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 6,7-dimethoxy-4-((7-methoxyquinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 32 as a brown solid (30 mg, 13% yield).

Provenance & Evidence