Methyl 2-pyrazinecarboxylate

White solid

Pyrazine-2-carboxylic acid (5 g, 40.3 mmol) was dissolved inMeOH (150 ml), and a few drops of H2SO4 were added. The resultingreaction mixture was refluxed for 2 h. Methanol was evaporated and the resulting reaction mixture was extracted withEtOAc, washed with saturated NaHCO3 solution, then with brineand dried over anhydrous Na2SO4. The solvent was removed invacuo to give the methyl pyrazine-2-carboxylate (5.5 g, yield98percent). 1H NMR (CDCl3, 400 MHz) d 9.32 (d, 1H, J = 1.5 Hz), 8.78(d, 1H, J = 2.4 Hz), 8.73 (dd, 1H, J = 2.4, 1.5 Hz), 4.04 (s, 3H).Methyl pyrazine-2-carboxylate (Formula 3). 20.0 g (805.8 mmole) of pyrazine-2-carboxylic acid was added to 160 mL of methanol, and 1.0 mL of a concentrated sulfuric acid was gradually dropwise added thereto with stirring. A reaction solution was refluxed at a temperature of 80 to 85°C for 5 hours. The reaction solution was cooled to a temperature of 20 to 22 °C and concentrated to a volume of 25mL. Then, 80 mL of methylenechloride and 40 mL of water were added to the resultant concentrate. The resultant solution was then neutralized by gradual addition of 40 mL of a saturated sodium hydrogen carbonate solution to get a pH of 8.5. An organic layer was separated and a water layer was extracted again with 40 mL of methylenechloride. The combined organic layer was dried over anhydrous magnesium sulfate, filtered, and washed with 20 mL of methylenechloride. A filtrate was concentrated to give 21.1 g of the titled compound as a pale brown solid (yield 94.8percent). Melting point: 60-61 °C• Charged MeOH (8.8 L) and OT-1 (1758 g) at RT. (0129) • Charged HREFERENCE EXAMPLE 8-42-pyrazinemethanol (Compound CD)Step 1; To methanol (8.0 mL), thionyl chloride (2.08 mL) was added dropwise under a nitrogen atmosphere at -10° C. and the mixture was stirred at the same temperature for 30 minutes. To this, 2-pyrazinecarboxylic acid (1.00 g, 8.06 mmol) was added at the same temperature and the mixture was stirred at room temperature for 72 hours. The reaction mixture was concentrated, a saturated aqueous sodium bicarbonate solution was added to the residue, and extraction with ethyl acetate was performed, followed by washing with brine and drying over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol 19/1) to give methyl 2-pyrazinecarboxylate (969 mg, yield: 87percent).General procedure: A catalytic amount of concentrated H2SO4 wasadded to a solution of carboxylic acids 16(a–j) (1.0 mmol)in 50 mL of methanol, and the mixture was refluxed for 6 h. It was allowed to cool. The saturated solution ofNaHCO3 was added to the reaction mixture, and it wasextracted with EtOAc (2 X 50 mL). The combined organiclayer was dried Na2SO4 and concentrated to obtain puremethyl esters 17(a–j).[0535] Synthesis of methyl pyrazine-2-carboxylate: [0536] To a stirred solution of pyrazine-2-carboxylic acid (5 g, 40.29 mmol) in MeOH (20 mL) was added concentrated HTo pyrazinecarboxylic acid (5.80 g, 46.5 mmol) in dichloromethane (100 mL) was added oxalyl chloride (5.10 mL, 60.4 mmol) followed by catalytic DMF. The reaction mixture was stirred at 23°C for 6 h. Methanol (30 mL) was then added, and the mixture was stirred for an additional 30 min. The reaction mixture was concentrated in vacuo. The residue was taken up in EtOAc (200 mL), and washed with sat. NaHCOSynthesis of methyl pyrazine-2-carboxylate: To a stirred solution of pyrazine-2-carboxylic acid (5 g, 40.29 mmol) in MeOH (20 mL) was added concentrated HExample 19.1Pyrazine-2-carboxylic acid methyl ester To pyrazine-2-carboxylic acid (15.0 g, 121 mmol) in DMF (150 mL) were added K

Molecular Weight:138.12
XLogP3:-0.2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:138.042927438
Monoisotopic Mass:138.042927438
Topological Polar Surface Area:52.1
Heavy Atom Count:10
Complexity:127
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes