Sodium Carbonate → 5-{3-[(3,5-Dimethoxybenzyl)oxy]phenyl}-7-(4-pyrrolidin-1-ylbutyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 5-bromo-7-(4-pyrrolidin-1-ylbutyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (70 mg, 0.21 mmol), 3-(3,5-dimethoxybenzyloxy)phenyl boronic acid (179 mg, 0.62 mmol), and tetrakis(triphenylphosphine)palladium(0) (23 mg, 0.021 mmol) in degassed DME (1.5 mL) was added aqueous Na2CO3 solution (2 M, 310 μL). The reaction was heated (80° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (25 mL) and water (25 mL). The layers were separated and the organic phase was washed dried (Na2SO4) and concentrated to dryness. The residue was purified by preparative HPLC using a gradient elution from 20% to 70% acetonitrile followed by preparative TLC eluting with 9:1 ethyl acetate/methanol (with 1% concentrated ammonium hydroxide) to obtain 29 mg (28%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 7.88 (s, 1 H), 7.36 (t, 1 H), 7.07-7.04 (m, 1 H), 7.03-6.96 (m, 2 H), 6.60 (d, 2 H), 6.55 (s, 1 H), 6.43 (t, 1 H), 5.07 (s, 2 H), 3.73 (s, s H), 2.88 (t, 2 h), 2.56-2.48 (m, 6 H), 1.78-1.65 (m, 6 H), 1.60-1.49 (m, 2 H); ES-MS m/z 502.2 [M+H]+, HPLC RT (min) 2.27.

Provenance & Evidence