Lithium Hydroxide → HCID 178440234, compound

Participants

Reaction Steps

To a solution of 6,7-dimethoxy-1-propylisoquinolin-3-ol RBO 35134 (434 mg, 1.75 mmol) in THF (13 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 6-(chloromethyl)-2-methylquinolinehydrochloride SLA 47080B (400 mg, 1.75 mmol) and a 2 N aq. LiOH solution (1.75 mL, 3.50 mmol) and the mixture was stirred at 160° C. for 1.5 h under microwave irradiation. After cooling to RT, THF was removed at 40° C. under vacuum and the residue was taken up in CH2Cl2 (50 mL), washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated 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 6,7-dimethoxy-4-((2-methylquinolin-6-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 0.49 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-((2-methylquinolin-6-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 80 as a yellow solid (28 mg, 3% yield).

Provenance & Evidence