Potassium Hydroxide → HCID 178486660, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 6,7-dimethoxy-1-methylisoquinolin-3-ol CCH 18060 (147 mg, 0.67 mmol) in toluene (3 mL) in a 10 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.70 mL, 1.40 mmol) at RT followed by 2-(chloromethyl)quinoline hydrochloride (158 mg, 0.74 mmol) and the mixture was stirred at 115° C. for 25 min under microwave irradiation. Another portion of a 2 N aq. KOH solution (0.30 mL, 0.60 mmol) was then added at RT followed by 2-(chloromethyl)quinoline hydrochloride (70 mg, 0.33 mmol) and the mixture was stirred at 115° C. for 10 min under microwave irradiation. After cooling to RT, the mixture was diluted with H2O (5 mL) and neutralised with a 10% aqueous citric acid solution before extraction with CH2Cl2 (50 mL). The 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 100:7) gave 49 mg of 6,7-dimethoxy-1-methyl-4-(quinolin-2-ylmethyl)isoquinolin-3-ol as a yellow solid. The free base (45 mg) was dissolved in MeOH (10 mL) in a 25 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.09 M HCl solution in MeOH (5.5 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 6,7-dimethoxy-1-methyl-4-(quinolin-2-ylmethyl)isoquinolin-3-ol hydrochloride 23 as a yellow solid (54 mg, 19% yield).

Provenance & Evidence