ethyl 2-(((tert-butoxycarbonyl)amino)methyl)-5-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-1H-pyrrole-3-carboxylate → 2-(((tert-butoxycarbonyl)amino)methyl)-5-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with ethyl 2-(((tert-butoxycarbonyl)amino)methyl)-5-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-1H-pyrrole-3-carboxylate (301b) (380 mg, 0.75 mmol) and LiOH monohydrate (157 mg, 3.74 mmol) in dioxane (5 mL) and water (2.5 mL). The tube was sealed and the reaction mixture was stirred and heated at 110° C. for 3 h. After cooling to RT, the reaction mixture was diluted with Et2O and water and the layers were separated. The Et2O layer was discarded. The aq. layer was acidified with 2 M HCl (aq.) and extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to give 2-(((tert-butoxycarbonyl)amino)methyl)-5-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid (308 mg, 0.64 mmol) as an orange solid. m/z (ESI, +ve) 480.2 (M+H)+. The orange solid (308 mg) was dissolved in 4 mL of dioxane and treated with a 4 M solution of HCl in 1,4-dioxane (4.68 mL, 18.72 mmol) at RT. The reaction mixture was stirred at RT overnight and was then concentrated. The solid was suspended with 1/1 Et2O/hexanes and collected by filtration to give 2-(aminomethyl)-5-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride (301c) (255 mg, 0.61 mmol, 82% yield) as a red solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.30 (br. s., 1H), 8.37 (t, J=5.77 Hz, 2H), 7.95 (dt, J=7.48, 0.76 Hz, 1H), 7.77 (t, J=6.16 Hz, 1H), 7.71 (dt, J=7.97, 0.81 Hz, 1H), 7.46 (t, J=7.82 Hz, 1H), 7.42 (dd, J=2.35, 0.39 Hz, 1H), 4.38-4.49 (m, 2H), 4.34 (q, J=5.35 Hz, 2H), 2.60 (s, 3H). 19F NMR (377 MHz, DMSO-d6) δ ppm −69.61 (s, 3F). m/z (ESI, +ve) 363.0 (M-NH2)′.

Provenance & Evidence