Citric Acid → HCID 178487430, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 6,7-dimethoxy-1-methylisoquinolin-3-ol CCH 18060 (200 mg, 912 μmol) in toluene (15 mL) in a 20 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 3-(chloromethyl)-7-methoxyquinoline hydrochloride MDE 32012 (245 mg, 1.00 mmol) and the mixture was stirred at 150° C. for 20 min under microwave irradiation. After cooling to RT, another portion of a 2 N aq. KOH solution (0.30 mL, 0.60 mmol) was added and the mixture was stirred at 150° C. for 20 min under microwave irradiation. After cooling to RT, the mixture was diluted with EtOAc (50 mL) and acidified by a 10% aqueous citric acid solution (5 mL) before neutralisation with a saturated aqueous NaHCO3 solution. The organic phase was isolated and the aqueous phase was further extracted with CH2Cl2 (50 mL). Both organic phases were washed with brine (10 mL), combined, dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:7N NH3 in MeOH=100:0 to 94:6) gave 23 mg of 6,7-dimethoxy-4-((7-methoxyquinolin-3-yl)methyl)-1-methylisoquinolin-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 0.09 M HCl solution in MeOH (4 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 6,7-dimethoxy-4-((7-methoxyquinolin-3-yl)methyl)-1-methylisoquinolin-3-ol dihydrochloride 29 as a brown solid (27 mg, 6% yield).

Provenance & Evidence