3-(chloromethyl)-6-methoxy-N-propylquinolin-2-amine → HCID 178456828, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 6,7-dimethoxy-1-propyl-isoquinolin-3-ol RBO 35134 (250 mg, 1.01 mmol) in THF (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added 3-(chloromethyl)-6-methoxy-N-propylquinolin-2-amine free base SLA 28178 (269 mg, 1.01 mmol) followed by a dropwise addition of n-Buli (1.6 M in hexane, 0.65 mL, 1.04 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) and 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 92:8) followed by a second purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5) provided, after evaporation, 70 mg of 6,7-dimethoxy-4-((6-methoxy-2-(propylamino)quinolin-3-yl)methyl)-1-propylisoquinolin-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 (0.40 mL). The reaction mixture was stirred for 5 min at RT then concentrated at 40° C. under vacuum to afford 6,7-dimethoxy-4-((6-methoxy-2-(propylamino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 52 as a yellow solid (26.6 mg, 5% yield).

Provenance & Evidence