Triethyl Phosphate → HCID 49838510, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 2-(4-(3-iodobenzyloxy)-2-methylphenethyl)-8-methylbenzo[f][1,7]naphthyridin-5-amine (1.0 equiv.) in triethyl phosphate (1.05 eq.) was added palladium acetate (0.08 eq.). The resulting reaction mixture was heated at 90° C. overnight. After the reaction was cooled down to room temperature, the residue was taken up in DCM (0.27 M) at 0° C., and was treated with TMSBr (11 equiv.). The reaction was warmed to room temperature over 2 hours, and then quenched with small amounts of MeOH. The DCM was removed by evaporation, and then added DMSO/water. The mixture was adjusted to pH 9 and directly purified on RP-HPLC using a C18 column, eluting with 10-40% 95:5 (MeCN/5 mM NH4OAc) in 10 mM NH4OAc (pH 9) gradient. The fractions containing the product were combined and concentrated in vacuo to give 3-((4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylphenoxy)methyl)phenylphosphonic acid (13) as a solid. 1H NMR (Dimethylsulfoxide-d6): δ 8.84 (s, 1H), 8.72 (s, 1H), 8.35 (d, 1H, J=8.4 Hz), 7.67 (d, 1H, J=12 Hz), 7.60-7.54 (m, 1H), 7.30-7.20 (m, 2H), 7.15 (d, 1H, J=8.4 Hz), 7.11 (d, 1 H, J=8.4 Hz), 7.04 (s, 1H), 6.84 (s, 1H), 6.77 (m, 1H), 4.99 (s, 2H), 3.12-2.92 (m, 4H), 2.44 (s, 3 H), 2.27 (s, 3H). LRMS [M+H]=514.2

Provenance & Evidence