Lithium Hydroxide → HCID 178437776, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 3-(chloromethyl)-N-isopropyl-6-methoxyquinolin-2-amine hydrochloride SLA 28190 (323 mg, 1.07 mmol) in THF (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added 1-ethyl-6,7-dimethoxyisoquinolin-3-ol SLA 28136 (250 mg, 1.07 mmol) followed by a 2 N aq. LiOH solution (1.07 mL, 2.14 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 (150 mL), washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent EtOAc:MeOH=100:0 to 94:6) followed by a second purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 93:7) provided, after evaporation, 60 mg of 1-ethyl-4-((2-(isopropylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxyisoquinolin-3-ol as a brown solid. This free base was dissolved in CH2Cl2 (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.49 M HCl solution in MeOH (1.04 mL). The reaction mixture was stirred for 5 min at RT then concentrated at 40° C. under vacuum to afford 1-ethyl-4-((2-(isopropylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxyisoquinolin-3-ol dihydrochloride 43 as a yellow solid (69 mg, 12% yield).

Provenance & Evidence