Reaktion #88582

Reaktionsgleichung

hydrochloric acid

HBr

(R)-4-((1-ethylpiperidin-2-yl)methoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile

sodium hydroxide

→

title compound

Ausbeute 32.0%

(R)-4-((1-ethylpiperidin-2-yl)methoxy)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile

Ausbeute 32.0%

Lösungsmittel

1,4-dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe cooled reaction mixture
2. 2
   Sonstigeproducing a cloudy precipitate
3. 3
   SonstigeThe solid was collected by centrifugation
4. 4
   workup.DISSOLUTIONdissolved in dimethylsulfoxide (2 mL)
5. 5
   Sonstigepurified by preparative HPLC [5-85% methanol in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min]

Vorschrift

(R)-4-((1-ethylpiperidin-2-yl)methoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (64 mg, 0.14 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 solid (15 mg, 32%). 1H NMR (500 MHz, d6-DMSO) δ 12.81 (s, 1H), 8.98 (s, 1H), 8.55 (d, J=5.7, 1H), 8.43 (s, 1H), 7.05 (d, J=5.8, 1H), 4.27 (m, 3H), 3.05 (m, 1H), 2.77 (m, 1H), 2.36 (m, 1H), 2.25 (m, 1H), 1.99 (m, 1H), 1.83 (m, 1H), 1.70 (m, 1H), 1.57 (m, 1H), 1.23 (m, 1H), 1.03 (t, J=7.1, 3H), 0.92 (d, J=6.6, 1H). LCMS (Method D): RT=6.63 min, M+H+=336.2.

Quelle