Lithium Hydroxide → HCID 178463390, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 3-(chloromethyl)-N-ethyl-6-methoxyquinolin-2-amine hydrochloride SLA 28166 (84 mg, 0.29 mmol) in THF (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added 6,7-dimethoxy-1-(methoxymethyl)isoquinolin-3-ol SMA 44012 (73 mg, 0.29 mmol) followed by a 2 N aq. LiOH solution (0.29 mL, 0.58 mmol) and the mixture was stirred at 160° 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 95:5) followed by a new purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5) provided 4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-(methoxymethyl)isoquinolin-3-ol. 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 (0.28 mL) and the mixture was stirred for 5 min at room temperature and concentrated at 40° C. under vacuum to afford 4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-(methoxymethyl)isoquinolin-3-ol dihydrochloride 67 as a yellow solid (9 mg, 6% yield).

Provenance & Evidence