Lithium Hydroxide → HCID 178437788, compound

Participants

Reaction Steps

To a solution of 1-ethyl-6,7-dimethoxyisoquinolin-3-ol SLA 28136 (288 mg, 1.18 mmol) in THF (13 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added 3-(chloromethyl)-6-methoxyquinoline hydrochloride SLA 47088B (275 mg, 1.18 mmol) and a 2 N aq. LiOH solution (1.20 mL, 2.40 mmol) and the mixture was stirred at 160° C. for 1.5 h under microwave irradiation. After cooling to RT, THF was then removed at 40° C. under vacuum and the solution was extracted with CH2Cl2 (50 mL), washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 94:6) followed by a new purification by column chromatography (RP 18, eluent CH3CN:H2O=100:0 to 34:66) gave 1-ethyl-6,7-dimethoxy-4-((6-methoxyquinolin-3-yl)methyl)isoquinolin-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 0.149 M HCl solution in MeOH (3.0 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 1-ethyl-6,7-dimethoxy-4-((6-methoxyquinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 85 as a brown solid (46.5 mg, 8% yield).

Provenance & Evidence