Lithium Hydroxide → HCID 178488007, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of N-(2-(3-(chloromethyl)-6-methoxyquinolin-2-ylamino)ethyl)acetamide hydrochloride SLA 41176 (115 mg, 0.33 mmol) in THF (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added 6,7-dimethoxy-1-methylisoquinolin-3-ol CCH18060 (73 mg, 0.33 mmol) followed by a 2 N aq. LiOH solution (0.33 mL, 0.66 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 CH2Cl2:MeOH=100:0 to 90:10) provided N-(2-(3-((3-hydroxy-6,7-dimethoxy-1-methylisoquinolin-4-yl)methyl)-6-methoxyquinolin-2-ylamino)ethyl)acetamide. This free base was dissolved in CH2Cl2 (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of 0.49 M HCl in MeOH (2 mL) and the solution was stirred for 5 min at RT then concentrated at 40° C. under vacuum to afforded N-(2-(3-((3-hydroxy-6,7-dimethoxy-1-methylisoquinolin-4-yl)methyl)-6-methoxyquinolin-2-ylamino)ethyl)acetamide dihydrochloride 73 as a yellow solid (19.5 mg, 10% yield).

Provenance & Evidence