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

Participants

Reaction Conditions

Reaction Steps

(R)-4-(1-methylpiperidin-3-ylmethoxy)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (45 mg, 0.1 mmol) was dissolved in 1,4-dioxane (0.2 mL) and then treated with 48% HBr(aq) (0.2 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 pale yellow solid (26 mg, 70% over two steps). 1H NMR (400 MHz, d6-DMSO) δ 8.97 (d, J=0.7, 1H), 8.54 (d, J=5.7, 1H), 8.44 (s, 1H), 7.04 (d, J=5.8, 1H), 4.28 (d, J=6.4, 2H), 2.88 (m, 1H), 2.65 (m, 1H), 2.27 (m, 1H), 2.19 (s, 3H), 1.97 (m, 2H), 1.83 (m, 1H), 1.74-1.66 (m, 1H), 1.59 (m, 1H), 1.28-1.18 (m, 1H), NH signal not observed. LCMS (method D): RT=7.182 min, M+H+=322.1.

Provenance & Evidence