Hydrogen Bromide → (R)-4-((1-methylpiperidin-2-yl)methoxy)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Participants

Reaction Conditions

Reaction Steps

(R)-4-((1-methylpiperidin-2-yl)methoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (197 mg, 0.44 mmol) was dissolved in 1,4-dioxane (0.5 mL) and then treated with 48% HBr(aq) (0.5 mL) and heated at 75° C. for 15 minutes. The cooled reaction mixture was then basified to pH ˜12 by dropwise addition of 6N sodium hydroxide and then immediately acidified to pH ˜8-9 by dropwise addition of concentrated hydrochloric acid, producing a cloudy precipitate. The solid was collected by centrifugation, dissolved in dimethylsulfoxide (2 mL), and purified by preparative HPLC [5-85% methanol in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min] to afford the title compound as a white solid (39 mg, 28%). 1H NMR (400 MHz, d6-DMSO) δ 12.80 (s, 1H), 8.98 (d, J=0.9, 1H), 8.55 (d, J=5.7, 1H), 8.47 (d, J=0.9, 1H), 7.07 (d, J=5.8, 1H), 4.39 (ddd, J=35.9, 10.4, 4.4, 2H), 2.84 (m, 1H), 2.34 (s, 3H), 2.16 (td, J=11.4, 3.3, 1H), 1.92-1.82 (m, 1H), 1.76 (m, 1H), 1.62 (m, 1H), 1.58-1.43 (m, 2H), 1.43-1.29 (m, 1H), 1.23 (s, 1H). LCMS (Method D): RT=7.48 min, M+H+=322.1.

Provenance & Evidence