Lithium Hydroxide → HCID 178440221, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 3-(chloromethyl)-2-ethyl-6-methoxyquinoline hydrochloride SMA 44014 (183 mg, 0.67 mmol) in THF (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added 6,7-dimethoxy-1-propylisoquinolin-3-ol RBO 35134 (166 mg, 0.67 mmol) followed by a 2 N aq. LiOH solution (0.67 mL, 1.34 mmol) and the mixture was stirred at 160° C. for 1.5 h under microwave irradiation. After cooling to room temperature, the mixture was diluted with CH2Cl2:MeOH=9:1 (150 mL), washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent EtOAc:MeOH=100:0 to 95:5) followed by a new purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5) provided after evaporation 4-((2-ethyl-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol. This free base was dissolved in CH2Cl2 (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.49 M HCl solution in MeOH (0.32 mL) and the mixture was stirred for 5 min at RT then concentrated at 40° C. under vacuum to afford 4-((2-ethyl-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 66 as a yellow solid (17 mg, 5% yield).

Provenance & Evidence