Acetic Anhydride → 1-(Acetamidomethyl)-4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxyisoquinolin-3-yl acetate

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-((4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-3-hydroxy-6,7-dimethoxyisoquinolin-1-yl)methyl)isoindoline-1,3-dione CCH 42006-1 (75 mg, 130 μmol) in EtOH (5 mL) in a 10 mL microwave vial equipped with a magnetic stirrer was added hydrazine monohydrate (26 μL, 536 μmol) and the mixture was stirred for 10 min at 130° C. under microwave irradiation. After cooling to RT, the reaction mixture was concentrated to dryness at 40° C. under vacuum. The residue CCH 42006-2 was dissolved in dry CH2Cl2 (4 mL) and half of the solution (around 65 μmol) was transferred in a 5 mL microwave vial equipped with a magnetic stirrer before addition of diisopropylaminomethyl-polystyrene resin (3 mmol/g, 86 mg, 258 μmol), DMAP (2 mg, 16 μmol) and acetic anhydride (34.5 μL, 365 μmol) and the reaction mixture was stirred for 20 min at 100° C. under microwave irradiation. After cooling to RT, the mixture was diluted with CH2Cl2 (30 mL), filtered through cotton wool, then washed with brine (5 mL), dried over Na2SO4, filtered, and concentrated under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 0:100) gave 1-(acetamidomethyl)-4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxyisoquinolin-3-yl acetate 56 as an off-white solid (25 mg, 72% yield).

Provenance & Evidence