5-Chloropyrazinoic acid → (R)-N-(3-(2-Amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-chloropyrazine-2-carboxamide

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

5-Chloropyrazine-2-carboxylic acid (367 mg, 2.31 mmol) was combined with MeOH (25 ml) to give a colorless solution. 4-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMTMM, 705 mg, 2.55 mmol) was added at 0° C. and the solution was stirred at 0° C. for 30 min. A solution of (R)-4-(5-amino-2-fluoro-phenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate A 8.1, 600 mg, 2.31 mmol) in MeOH (10 ml) was added dropwise and the reaction mixture was stirred overnight at 0° C. Sat. aq. NaHCO3 was added and the product was extracted with three portions of AcOEt. The combined organic layers were dried over Na2SO4 and concentrated under vacuum. The crude material was purified by flash chromatography (SiO2, 50 g, 50 to 100% EtOAc in heptane). White solid (540 mg, 58%). MS (ISP): m/z=400.1 [M+H]+.

Herkunft & Nachweise