Triethylamine → methyl 3-[7-[3-(dimethylamino)prop-1-yn-1-yl]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoate

Participants

Reaction Conditions

Reaction Steps

A mixture of the methyl 4-methyl-3-[1-oxo-7-{[(trifluoromethyl)sulfonyl]oxy} isoquinolin-2(1H)-yl]benzoate (284 mg), PdCl2(PPh3)2 (13 mg), CuI (6 mg) and triethylamine (449 μl) were stirred in acetonitrile (4.2 ml) for 20 minutes. 1-Dimethylamino-2-propyne (69 μl) in acetonitrile (2.8 mL) was added dropwise and the reaction was stirred at 80° C. for 22 hours. LiCl (81 mg) was added and stirring continued at 80° C. for 1.5 hours. PdCl2(PPh3)2 (13 mg), CuI (6 mg) and 1-dimethylamino-2-propyne (69 μl) was added and stirring continued for a further 22 hours. The reaction mixture was concentrated and the residue was dissolved in ethyl acetate, washed with water (×5), brine, dried (magnesium sulfate), and concentrated to an oil. Purification by column chromatography on a silica column eluting using a gradient of ethyl acetate to 10% methanol/ethyl acetate gave methyl 3-[7-[3-(dimethylamino)prop-1-yn-1-yl]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoate as a light brown solid (126 mg); NMR Spectrum: (DMSOd6) 2.15 (s, 3H), 2.27 (s, 6H), 3.52 (s, 2H), 3.86 (s, 3H), 6.79 (d, 1H), 7.43 (d, 1H), 7.60 (d, 1H), 7.79 (m, 2H), 7.87 (s, 1H), 7.99 (d, 1H), 8.23 (s, 1H); Mass Spectrum: M+H+ 375.

Provenance & Evidence