Potassium Hydroxide → HCID 178486662, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 6,7-dimethoxy-1-methylisoquinolin-3-ol CCH 18060 (200 mg, 0.912 mmol) in DME (5 mL) in a 10 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.95 mL, 1.90 mmol) at RT followed by 6-(chloromethyl)quinoline hydrochloride (234 mg, 1.093 mmol, prepared by stirring quinolin-6-yl methanol (330 mg) in SOCl2 (1 mL) for 1 h at RT, then concentration under vacuum and repeated coevaporation with CH2Cl2 and the mixture was stirred at 115° C. for 25 min under microwave irradiation. After cooling to RT, the mixture was diluted with H2O (5 mL) before extraction with EtOAc (50 mL). The organic phase was washed with brine (10 mL) and the aqueous phase was further extracted with CH2Cl2 (50 mL). The dichloromethane phase was washed with brine (10 mL), combined with the first organic phase, dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 92:8) gave 37 mg of 6,7-dimethoxy-1-methyl-4-(quinolin-6-ylmethyl)isoquinolin-3-ol as a yellow solid. This free base 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 (4.0 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-6-ylmethyl)isoquinolin-3-ol dihydrochloride 24 as a brown solid (44 mg, 11% yield).

Provenance & Evidence