7-tert-Butyl 1-methyl 3-(trifluoromethyl)-5H,6H,7H,8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylate synthesis

Yield:1174039-45-2 67%

Reaction Conditions:

with potassium carbonate;dicobalt octacarbonyl in methanol at 60; for 6.25 h;

Steps:

27.3 3-Trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylic acid 7-tert-butyl ester 1-methyl ester

Octacarbonyldicobalt (5.54 g, 16.2 mmol) and potassium carbonate (11.2 g, 81.1 mmol) was dissolved in 100 mL of methanol under stirring. The reaction mixture was stirred for 15 minutes at 60 °C, and 1-bromo-3-trifluoromethyl-5,6-dihydro -8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester 27b (3 g, 8.11 mmol) and methyl chloroacetate (5.25 g, 48.6 mmol) were then added to the solution. The reaction mixture was reacted for 6 hours under a carbon monoxide atmosphere and monitored by thin layer chromatography until the disappearance of the starting materials. After cooling to room temperature, the reaction mixture was filtered through a pad of silica gel, rinsed with methanol. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylic acid 7-tert-butyl ester 1-methyl ester 27c (1.92 g, yield 67%) as a white solid. (Reference: J. Organomet. Chem, 1985, 293) MS m/z (ESI): 350.5 [M+1].

References:

EP2230241,2010,A1 Location in patent:Page/Page column 46-47