Hydrogen Bromide → (S)-3-Bromo-4-(3-(ethylamino)pyrrolidin-1-yl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Participants

Reaction Conditions

Reaction Steps

(S)-tert-butyl 1-(3-bromo-6-cyano-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-4-yl)pyrrolidin-3-yl(ethyl)carbamate (65 mg, 0.1 mmol) was dissolved in 1,4-dioxane (0.3 mL) and then treated with 48% HBr(aq) (0.3 mL) and heated at 55° C. for 20 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 (23 mg, 26% over two steps). 1H NMR (500 MHz, d6-DMSO) δ 8.97 (s, 1H), 8.78 (s, 1H), 8.60 (s, 1H), 3.79-3.73 (m, 2H), 3.62-3.51 (m, 3H), 3.43 (m, 1H), 2.72-2.59 (m, 2H), 2.26 (m, 1H), 1.97 (m, 1H), 1.14 (t, J=7.1, 3H), NH signal not observed. LCMS (Method D): RT=7.535 min, M+H+=385.0/387.0.

Provenance & Evidence