Reference of 13924-94-2, The chemical industry reduces the impact on the environment during synthesis 13924-94-2, name is Methyl 5-aminopyrazine-2-carboxylate, I believe this compound will play a more active role in future production and life.
To a solution of Int-1 (100 g, 1.063 mmol)) in DME (400 mL) was added Int-2 (155 g, 1.595 mmol) at room temperature. The reaction mixture was heated to 85 C. and stirring was continued overnight. The volatiles were concentrated under reduced pressure, then residue was diluted with water (500 mL) and dichloromethane (500 mL). The pH was adjusted to neutral by using sat. NaHCO3. The organic layer was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified through silica gel column chromatography, eluted with ethyl acetate to afford Int-3 (40 g, 28.5%) as syrup. To a solution of Int-3 (40 g, 0.303 mol) in acetonitrile (200 mL) was added N-Iodo succinamide (81 g, 0.3636 mol) at room temperature, and then stirred for 1 hour. The reaction mixture was poured into water and stirred for 30 minutes. The precipitated solids were filtered and solids were triturated in ethyl acetate (1 L), filtered solid, and washed with ethyl acetate. Then filtrate was washed with 10% Na2CO3 solution (250 mL), water, dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford Int-4 (18.1 g, 23%) as a solid. Mass (m/z): 259 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 8.43 (d, J=8 Hz, 1H), 7.69-7.53 (m, 2H), 7.23 (t, J=6.6 Hz, 1H), 2.42 (s, 3H). To a suspended solution of Int-5 (12 g, 46.51 mmol) in IPA: water (80 mL: 30 mL) was added Pd Cl2(dppf).DCM (7.5 g, 9.3 mmol), tertiary butyl amine (4.9 g, 69.76 mmol) and Na2CO3 (7.3 g, 69.76 mmol) at room temperature. The reaction mixture was heated to 100 C. and stirring was continued overnight. The reaction mixture was allowed to room temperature, and then diluted with dichloromethane (250 mL) and water. The organic layer was separated, washed with 10% Na2CO3 solution (75 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified through silica gel column chromatography, eluted product with ethyl acetate to afford Int-6 (4.8 g, 42.4%) as a solid. Mass (m/z): 244 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 8.51 (t, J=5 Hz, 2H), 7.71 (s, 1H0, 7.63-7.55 (m, 2H), 7.34 (t, J=7 Hz, 1H), 6.94 (t, J=7 Hz, 1H), 2.43 (s, 3H). To a solution of Int-7 (1 g, 5.797 mmol) in THF (10 mL) was added 4-methoxy benzyl amine (1.98 g, 14.49 mmol) at room temperature and, then stirred overnight. The reaction mixture was filtered, concentrated under reduced pressure. The residue was purified through silica gel column chromatography, eluted product with 50% ethyl acetate/dichloromethane to afford Int-8 (800 mg, 50.6%) as a solid. Mass (m/z): 274 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 8.6 (s, 1H), 8.61-8.42 (brs, 1H), 8.01 (s, 1H), 7.23 (d, J=8.5 Hz, 2H), 6.83 (d, J=8.4 Hz, 2H). To a solution of Int-8 (800 mg, 2.925 mmol) in trifluoro acetic acid (5 mL) was stirred for 1 hour at 60 C. The reaction mixture was allowed to room temperature, and then quenched with solid sodium bicarbonate. The reaction mixture was diluted with ethyl acetate and water. The organic layer was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure rotavapour to afford Int-9 (350 mg, 78%) as a solid. Mass (m/z): 154 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 8.51 (s, 1H), 8.7.83 (s, 1H), 7.39 (brs, 2H), 3.79 (s, 3H). To a solution of Int-6 (1.58 g, 6.535 mmol) in 1,4-dioxane (25 mL) was added palladium acetate (238 mg, 1.045 mmol), Xantpos (498 mg, 1.045 mmol), Int-9 (1 g, 6.535 mmol) and cesium carbonate (3.21 g, 9.802 mmol) at room temperature. The reaction mixture was heated to 100 C. and stirring was continued for 18 hours. The reaction mixture was concentrated under reduced pressure, then residue was diluted with ethyl acetate. The precipitated solids were filtered, then washed with water (25 mL) and dried under vacuum. The solids were purified through silica gel column chromatography, eluted product with 3% methanol/dichloromethane to afford Int-10 (200 mg, 8.5%) as a solid. Mass (m/z): 361 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 10.8 (brs, 1H), 9.06 (s, 1H), 8.09 (s, 1H), 8.59-8.4 (m, 2H), 8.01 (s, 1H), 7.6 (d, J=7.4 Hz, 1H), 7.7.29-7.2 (m, 2H), 6.98 (t, J=7 Hz, 1H), 3.81 (s, 3H). To a solution of Int-10 (200 mg, 0.555 mmol) in methanol (4 mL) and dichloromethane (10 mL) was added hydroxyl amine solution (aqueous 50%) (4 mL) and reaction mixture was stirred for 20 minutes at 0 C. Then sodium hydroxide solution (3 mL) was added and the reaction mixture was allowed to room temperature, then stirred for 5 hours. The volatiles were concentrated under reduced pressure, then adjusted pH to neutral by using 1N HCl at 0 C. The precipitated solids were filtered, washed with water, dichloromethane and hexanes to afford the title compound (150 mg, 75%) as a solid. Mass (m/z): 362 [M++1]. (1H NMR 200 MHz (dmso-d6): delta 10.96 (brs, 1H), 9.01 (s, 1H), 8.72 (s, 1H), 8.54 (d, J=6.6 Hz, 1H), 8.47 (d, J=5.4 Hz, 1H), 7.99 (s, 1H), 7.6 (d, J=8.8 Hz, 1H), 7.33 (t, J=7.6 Hz, 1H), 7.24 (d, J=3.8 Hz, 1H), 6.99 (t, J=7 Hz, 1H), 6.42 (s,…
In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, Methyl 5-aminopyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.
Reference:
Patent; Melvin, JR., Lawrence S.; Graupe, Michael; Venkataramani, Chandrasekar; US2010/29638; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem