Electric Literature of 5521-58-4, These common heterocyclic compound, 5521-58-4, name is 5-Methylpyrazin-2-amine, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
Examples (2R)-2-(3-Chloro-4-cyclopropanesulfonylphenyl)-3-(tetrahydropyran-4-yl)propionic acid (Preparation 9) was coupled with amines selected from 2-amino-5-methylpyrazine, 3- amino-5-methylisoxazole, 3-aminoisoxazole, 2-amino-5-methylthiazole, 3-amino-6- methylpyridazine, l-methyl-3-aminopyrazole, 2-aminopyrazine and 4-aminopyrimidine using the following procedure to provide Examples 1-8.CH2Cl2 (6OmL) and DMF (0.08mL, 1.064mmol, 1.2 eq) were cooled to -100C and oxalylchloride slowly added (0.09mL, 0.465mol, 1.2 eq). After stirring for 15 min the reaction mixture was cooled to -300C and (2R)-2-(4-cyclopropanesulfonylphenyl)-3- (tetrahydropyran-4-yl)propionic acid (Preparation 8, 0.300g, 0.886mmol, 1.0 eq) was added.The reaction was stirred at -300C for 45min then pyridine (1.395mol, 0.3ImL in ImL CH2Cl2, 4.5eq) and the amine (4.43mmol, 5.0eq) were slowly added in parallel at -400C. The reaction mixture was stirred for 15min then the ice bath removed. The reaction mixture was stirred for 2h until it reached rt. The solvent was removed under partial vacuum and the crude mixture dissolved in EtOAc (1OmL) and aqueous HCl (1.5mL). The layers were separated and the aqueous phase extracted with EtOAc (5mL). The organic fractions were combined and washed with H2O (1OmL), saturated aqueous NaHCO3 (2 x 1OmL), water (5mL) and brine (5mL) and dried (MgSOzi). Purification was by flash chromatography (EtOAc :heptane, 2:1) and/or recrystallisation.
Statistics shows that 5-Methylpyrazin-2-amine is playing an increasingly important role. we look forward to future research findings about 5521-58-4.
Reference:
Patent; PROSIDION LTD; WO2007/51846; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem