Water → HCID 178486667, compound

Participants

Reaction Steps

To a stirred solution of 4-((6-bromopyridin-2-yl)methyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol CCH 34150 (53 mg, 136 μmol) in EtOH (0.9 mL) in a 20 mL microwave vial equipped with a magnetic stirrer were added 4-pyridinylboronic acid (17 mg, 138 μmol), Pd(PPh3)2Cl2 (10 mg, 14 μmol), a 2 N aq. Na2CO3 solution (0.30 mL, 0.60 mmol), H2O (2.7 mL) and dimethoxyethane (3.5 mL) and the resulting mixture was stirred at 140° C. for 25 min. After cooling to RT, the mixture was diluted with EtOAc (30 mL) and the solution was filtered through a celite plug, then washed with brine (10 mL). The organic layer was isolated and the celite plug was then further washed with CH2Cl2 (50 mL) and the organic layer was washed with brine (20 mL). The organic layers were then combined, dried over Na2SO4, filtered, and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 92:8) provided 16 mg of 4-(2,4′-bipyridin-6-ylmethyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol. This free base was dissolved in MeOH (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 (0.5 mL). The reaction mixture was stirred for 5 min at RT then concentrated at 40° C. under vacuum to afford 4-(2,4′-bipyridin-6-ylmethyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol trihydrochloride trihydrochloride 14 as a pale brown solid (20 mg, 30% yield).

Provenance & Evidence