Methanol → 2-(1-((tert-butoxycarbonyl)amino)ethyl)-5-(3-((2,2-difluoroethyl)amino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with ethyl 2-(1-((tert-butoxycarbonyl)amino)ethyl)-5-(3-((2,2-difluoroethyl)amino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (950 mg, 1.887 mmol) and LiOH monohydrate (396 mg, 9.43 mmol) in dioxane (8.0 mL) and water (4.00 mL). The reaction mixture was stirred and heated in at 110° C. for 80 min. LC-MS indicated >87% conversion to the desired carboxylic acid m/z (ESI, +ve ion) 476.1 (M+H)+. The reaction mixture was transferred to a 250 mL RBF, using MeOH and concentrated to dryness affording 2-(1-((tert-butoxycarbonyl)amino)ethyl)-5-(3-((2,2-difluoroethyl)amino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid as an orange solid. The orange solid was treated with 4.0 M HCl solution in 1,4-dioxane (11.79 mL, 47.2 mmol) at RT and stirred for 30 min. The reaction mixture was concentrated to give 2-(1-aminoethyl)-5-(3-((2,2-difluoroethyl)amino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride (382b) as a red-orange solid. It was used in the subsequent step without further purification assuming quantitative yield. 19F NMR (377 MHz, DMSO-d6) δ ppm −120.68 (1F, s). (m/z (ESI, +ve ion) 376.1 (M+H)+).

Provenance & Evidence