Hydrogen Bromide → (R)-4-(piperidin-2-ylmethoxy)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Participants

Reaction Conditions

Reaction Steps

(R)-4-(piperidin-2-ylmethoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (467 mg, 1.1 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 (122 mg, 37%). 1H NMR (400 MHz, d6-DMSO) δ 8.97 (d, J=0.7, 1H), 8.54 (m, 2H), 7.05 (d, J=5.8, 1H), 4.30-4.18 (m, 2H), 3.11 (m, 1H), 3.03 (m, 1H), 2.69-2.60 (m, 1H), 1.79 (m, 2H), 1.58 (m, 1H), 1.45-1.33 (m, 2H), 1.33-1.21 (m, 1H). LCMS (Method D): RT=7.41 min, M+H+=308.1.

Provenance & Evidence