Triethylamine → 2-(2,6-dichloroanilino)-1,6-dimethyl-7-((E)-3-{methyl[3-(methylamino)propyl]amino}-1-propenyl)-8,9-dihydro-1H-imidazo[4,5-h]isoquinolin-9-one

Participants

Reaction Steps

A solution of tris(dibenzylidineacetone)dipalladium (0) (0.016 g, 0.01697 mmol) in tetrahydrofuran under nitrogen atmosphere was treated with triphenylphosphine (0.007 g, 0.0255 mmol). The reaction mixture was stirred for about 20 minutes under a nitrogen atmosphere. A solution of 1-[2-(2,6-dichloroanilino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinolin-7-yl]allyl acetate (Snow et al., 2001) (0.080 g, 0.1697 mmol) in tetrahydrofuran was added to the palladium solution. Triethylamine (0.052 g, 0.509 mmol) and N,N′-dimethyl-1,3-propanediamine (0.087 g, 0.8485 mmol) were added to the reaction solution. The reaction mixture was stirred at room temperature for 15 hours under a nitrogen atmosphere. Tetrahydrofuran was removed from the reaction mixture under reduced pressure. Acetic acid (0.5 mL) and dimethylformamide (5 mL) were added. The reaction mixture was filtered through a Gelman filter disk and was then purified by preparative HPLC chromatography. The preparative column afforded 0.012 g (14%) of pure 13, 2-(2,6-dichloroanilino)-1,6-dimethyl-7-((E)-3-{methyl[3-(methylamino)propyl]amino}-1-propenyl)-8,9-dihydro-1H-imidazo[4,5-h]isoquinolin-9-one. 1H NMR (CDCl3, 400 MHz) δ 7.8572-7.8355 (d, 1H J=8.68 Hz), 7.5408-7.5189 (d, 1H, J=8.76 Hz), 7.399-7.366 (m, 2H), 7.118-7.078 (t, 1H) 6.786-6.746 (m, 1H), 6.312-6.256 (m, 1H), 4.288 (s, 3H), 3.213-3.199 (m, 2H), 2.696-2,663 (t, 2H), 2.518-2.483 (t, 2H), 2.443 (s, 3H), 2.377 (s, 3H), 2.24 (s, 3H), 1.740-1.689 (m, 2H)); LCMS (Thermoquest AQA single-quad MS, Genesis C18 column, 3 μm particle size, 33×4.6 mm; 70% 50 mM ammonium acetate in water to 95% CH3CN over 6 min, 0.8 to 0.5 mL/min) Rt 2.05 min (100%), M+ 513.5 and 515.5.

Provenance & Evidence