At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl imidazo[1,2-a]pyrazine-3-carboxylate, and friends who are interested can also refer to it.
Synthetic Route of 1286754-14-0, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 1286754-14-0 name is Ethyl imidazo[1,2-a]pyrazine-3-carboxylate, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.
To a suspension of imidazo[1,2-a]pyrazine-3-carboxylic acid ethyl ester (0.21 g) and a solution of 4 mol/L hydrogen chloride in ethyl acetate (360 muL) in ethanol (3 mL) was added 10% palladium carbon (0.080 g) at room temperature, and the mixture was stirred overnight under hydrogen atmosphere. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. To the residue were added tetrahydrofuran (3 mL), triethylamine (460 muL) and benzyloxycarbonyl chloride (250 muL), and the mixture was stirred overnight at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by aminopropyl silica gel column chromatography (eluent:ethyl acetate/n-hexane=60/40 to 85/15) to afford 5,6-dihydro-8H-imidazo[1,2-a]pyrazine-3,7-dicarboxylic acid 7-benzyl-3-ethyl ester (0.16 g). To a solution of 5,6-dihydro-8H-imidazo[1,2-a]pyrazine-3,7-dicarboxylic acid 7-benzyl-3-ethyl ester (0.16 g) in ethanol (3 mL) was added an aqueous solution of 2 mol/L sodium hydroxide (315 muL). The mixture was stirred for 30 minutes under reflux, and allowed to cool to room temperature. To the mixture was added 2 mol/L hydrochloric acid (315 muL), and concentrated under reduced pressure to afford 5,6-dihydro-8H-imidazo[1,2-a]pyrazine-3,7-dicarboxylic acid 7-benzyl ester (0.146 g). To a solution of (R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride (0.108 g) and triethylamine (0.049 g) in methanol (2 mL) was added benzaldehyde (0.052 g), and the mixture was stirred for 30 minutes at 65 C. The reaction mixture was allowed to cool to room temperature. To the mixture were added 5,6-dihydro-8H-imidazo[1,2-a]pyrazine-3,7-dicarboxylic acid 7-benzyl ester (0.146 g) and 4-phenylcyclohexen-1-ylisocyanide (0.089 g). The mixture was stirred overnight at 65 C., then allowed to cool to room temperature, and concentrated under reduced pressure. To the obtained residue were added tetrahydrofuran (4 mL), water (100 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (500 muL), and the mixture was stirred for 30 minutes at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by aminopropyl silica gel column chromatography (eluent: methanol/ethyl acetate=4/96) to afford 3-{N–[(R)-carbamoylphenylmethyl]-N–[(R)-6-chloro-4-fluoroindan-1-yl]car- bamoyl}-5,6-dihydro-8H-imidazo[1,2-a]pyrazine-7-carboxylic acid benzyl ester (0.038 g) as a low polarity diastereomer. To a suspension of 3-{N–[(R)-carbamoylphenylmethyl]-N–[(R)-6-chloro-4-fluoroindan-1-yl]car- bamoyl}-5,6-dihydro-8H-imidazo[1,2-a]pyrazine-7-carboxylic acid benzyl ester (0.038 g) in tetrahydrofuran (3 mL) was added 10% palladium carbon (0.020 g) at room temperature, and the mixture was stirred for a day under hydrogen atmosphere. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by aminopropyl silica gel column chromatography (eluent: methanol/ethyl acetate=0/100 to 20/80) to afford the title compound (0.23 g).
At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl imidazo[1,2-a]pyrazine-3-carboxylate, and friends who are interested can also refer to it.
Reference:
Patent; Kissei Pharmaceutical Co., Ltd; Hirasawa, Hideaki; Kawamura, Naohiro; Kobayashi, Junichi; (160 pag.)CN105263901; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem