Lithium Hydroxide → HCID 178437770, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-ethyl-6,7-dimethoxyisoquinolin-3-ol SLA 28136 (284 mg, 1.22 mmol) in toluene (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. LiOH solution (1.20 mL, 2.40 mmol) at RT followed by 7-(chloromethyl)-N-methyl-[1,3]dioxolo[4,5-g]quinolin-6-amine hydrochloride CCH 34158B (350 mg, 1.22 mmol) and the mixture was stirred at 150° C. for 1.5 h under microwave irradiation. After cooling to RT, the mixture was diluted with CH2Cl2:MeOH=9:1 (80 mL) and the organic solution was washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:7 N NH3 solution in MeOH=100:0 to 95:5) gave 1-ethyl-6,7-dimethoxy-4-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)isoquinolin-3-ol. This free base was dissolved in MeOH (6 mL) in a 25 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.19 M HCl solution in MeOH (5 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum. Recrystallization from a mixture of MeOH:Et2O afforded 1-ethyl-6,7-dimethoxy-4-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)isoquinolin-3-ol dihydrochloride 61 as a pale brown solid (104 mg, 16% yield).

Provenance & Evidence