2-Pyrazinecarboxylic acid, 5-methyl-, ethyl ester

The reaction was carried out, under nitrogen, in a 2 L.x.4 neck flask equipped with a mechanical stirrer, water condenser (with gas inlet), and a thermocouple. The reactor was charged with 5-methylpyrazinecarboxylic acid (300.84 g), AMBERLYST.(R). 15 ion exchange resin (60.17 g), and ethanol (1004 g). The mixture was stirred at reflux for about 16 h after which the reaction was found to be complete by GC or GC/MS. The resin was removed by pressure filtration and rinsed with ethanol. The rinse was added to the alcohol solution of the ester. Evaporation of the solvent under reduced pressure gave 336.7 g (93percent) of 5-methylpyrazinecarboxylic acid, ethyl ester that was suitable for use in the following examples. It was also possible to pass the material through a thin film evaporator at 125° C./3 mm. The material from this distillation was almost colorless and crystallizes at about 20° C.A. Ethyl 5-methyl-2-pyrazinecarboxylate 5-methyl pyrazine-2-carboxylic acid (6.65 g, 48.14 mmol) was refluxed in 50 mL of EtOH containing a few drops of H2SO4 for 5h and then cooled and concentrated. The residue was redissolved in EtOAc and washed 1 x NaHCO3, 1 x brine and the organics dried (Na2SO4), filtered and concentrated to give the title compound (7.05 g, 42.42 mmol, 88percent yield) as a pale yellow oil :'H NMR (CDCI3, 400 MHz) 8 9.16 (s, 1H), 8.55 (s, 1H), 4.47 (dd, J= 14.1, 7.1 Hz), 2.64 (s, 3H), 1.42 (t, J = 7. 2 Hz, 3H).The reaction is carried out, under nitrogen, in a 1 L.x.4 neck flask equipped with a mechanical stirrer, water condenser (with gas inlet), and a thermocouple. The reactor is charged with 5-methylpyrazinecarboxylic acid (100 g), ethanol (300 g) and sulfuric acid (2 g). The contents are refluxed for eight hours at 78° C. The reaction mixture is cooled to ambient temperature and sodium bicarbonate (4 g) is added. About 75percent of the solvent is removed under reduced pressure and the resulting suspension is allowed to stand overnight. The solids are filtered and washed with cold methanol (2.x.80 g). Drying under oven (25 inches of Hg) yielded 101.25 g (84percent) of 5-methyl-2-pyrazonecarboxylic acid, ethyl ester.To the solution of 5-methyl-2-pyrazine carboxylic acid (1) (0.01 mol) in absolute ethyl alcohol (10 mL), conc. H2SO4 (2 mL) was added. The mixture was refluxed for 4 hwith constant stirring. After completion of the reaction (monitored by the TLC), the mixture was poured into ice-cold water. Crude product was collected by filtration, washed with 10 percent NaHCO3 solution, dried and recrystallized from ethyl alcohol to get pure 5-methyl-2-pyrazine carboxylic acid ethyl ester (2).A mixture of 5-methyl-2-pyrazinecarboxylic acid ethyl ester (2) (0.01 mol) and hydrazine hydrate (0.02mol) in ethyl alcohol (20 mL) was refluxed for 3 h with consistent stirring. After realization of the reaction (examined by the TLC), the reaction mixture is cooled to room temperature and filtered. The crude product was recrystallized from ethanol to offer pure 5-methyl-2-pyrazine carboxylic acid hydrazide (3).

Molecular Weight:166.18
XLogP3:0.6
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:166.074227566
Monoisotopic Mass:166.074227566
Topological Polar Surface Area:52.1
Heavy Atom Count:12
Complexity:161
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes