Bromotrimethylsilane → 2-(5-Amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)ethylphosphonic acid

Participants

Reaction Steps

To a solution of diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)ethylphosphonate (3-3) (1.0 equiv.) in DCM (0.02 M) at 0° C. was added TMSBr (10 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 DMSO/water was added. 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 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)ethylphosphonic acid (11) as a solid. 1H NMR (Dimethylsulfoxide-d6): δ 9.66 (s, 1H), 9.30 (s, 1H), 8.95 (s, 1H), 8.78 (s, 1H), 8.50 (d, 1H, J=8.4 Hz), 7.54 (s, 1H), 7.45 (d, 1H, J=8.4 Hz), 7.02 (d, 1H, J=8.4 Hz), 6.69 (d, 1H, J=2.8 Hz), 6.61 (dd, 1H, J=2.8, 8.4 Hz), 3.64 (s, 3H), 3.14-3.06 (m, 2H), 3.00-2.90 (m, 4H), 2.22 (s, 3H), 2.02-1.92 (m, 2H). LRMS [M+H]=452.2

Provenance & Evidence