2,3-Dibromo-5,6-dihydro-8H-imidazo[1,2-a]pyrazine-7-carboxylic acid tert-butyl ester synthesis

Yield:1250999-20-2 15%

Reaction Conditions:

with isopropylmagnesium chloride in tetrahydrofuran at -25; for 0.466667 h;Inert atmosphere;

Steps:

25.1 Step 1) 2-bromo-7-(tert-butoxycarbonyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine

To a solution of 2,3-dibromo-7-(tert-butoxycarbonyl)-5, 6,7,8- tetrahydroimidazo[l,2-a]pyrazine (1.47 g, 3.86 mmol) in anhydrous THF (20 mL) was added 'PrMgCl (2 mL, 4 mmol) dropwise at -25 °C over 5 min under ₂ atmosphere. The mixture was stirred at -25 °C for 10 min, additional amount of 'PrMgCl (1.47 mL, 2.94 mmol) was then added to the mixture over 3 min. The reaction was continued to stir at -25 °C for 10 min before being quenched with H₂0 (2 mL). The solvent was decanted, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (v/v) = 3/1) to give the title compound as colorless colloidal (0.18 g, 15%). MS (ESI, pos., ion.) m/z: 302 [M + H]⁺; NMR (400 MHz, CDC1₃) δ (ppm): 6.81 (s, 1H), 4.63 (s, 2H), 3.95-3.93 (t, J= 5.2 Hz, 2H), 3.83-3.81 (t, J= 5.2 Hz, 2H), 1.46 (s, 9H).

References:

WO2014/89324,2014,A1 Location in patent:Paragraph 0312