METHYL 3-AMINO-5,6-DIMETHYLPYRAZINE-2-CARBOXYLATE synthesis

Yield:6294-72-0 87.3%

Reaction Conditions:

with tris-(dibenzylideneacetone)dipalladium⁽⁰⁾;XPhos in 1,4-dioxane at 110;Inert atmosphere;

Steps:

A2-2.1 Step 1:

To a mixture of methyl 3-amino-5,6-dichloro-pyrazine-2-carboxylate (4 g, 18.0 mmol, 1.0 eq) and tetramethylstannane (8.05 g, 45.0 mmol, 2.5 eq) in 1,4-dioxane (50 mL) were added X-phos (3.43 g, 7.2 mmol, 0.4 eq) and Pd₂(dba)₃(1.03 g, 1.8 mmol, 0.1 eq). The mixture was degassed and stirred under N2, then warmed up to 110^oC and stirred overnight. LCMS showed the main peak was the desired product and no starting material remained. The mixture was cooled to room temperature, diluted with water (50 mL), and extracted with CH₂Cl2 (100 mL×3). The combined organics were washed with NaHCO3(aq) (100 mL) and brine (100 mL), dried over Na2SO4, and concentrated in vacuo to afford the crude product. The crude product was purified by FCC (Petroleum ether:EtOAc = 52:48) to afford the desired product (3 g, 87.3%) as a yellow solid. LCMS: M+H=182, Ref. time=0.85

References:

WO2022/236272,2022,A2 Location in patent:Paragraph 00469; 00574