Pyrazine-2-carbaldehyde

brown liquid

Method 54; Pvrazine-2-carboxaldehyde oxime A IN solution of lithium aluminium hydride in THF (73. 8ml, 73.8mmol) was added to a suspension of methyl pyrazine-2-carboxylate (20g, 145mmol) in anhydrous THF (300. 0ml) at-78°C keeping the reaction temperature below-72°C. On completion of addition the reaction mixture was left to stir at-78°C for a further 20 minutes and then quenched with glacial acetic acid (20. 0ml). The resulting mixture was warmed to room temperature and the volatiles removed by evaporation. The residue was dissolved in 3N hydrochloric acid (116ml) and extracted with DCM. The extracts were combined, washed with saturated aqueous sodium hydrogen carbonate solution and the solvent evaporated. The residue was purified by chromatography on silica gel eluting with DCM/diethylether (100: 0 then 80: 20 and then 0: 100) to give pyrazine-2-carboxaldehyde (15.67g, 100percent). This was immediately dissolved in chloroform (200ml) cooled to 0°C and hydroxylamine mono-hydrochloride (11. 02g, 159. 5mmol) and triethylamine (24. 2ml, 117. 4mmol) were added. The reaction mixture was then stirred at ambient temperature for 0.5 hour, and the solvent removed by evaporation. The residue suspended in diethylether (500ml) and the insolubles removed by filtration. The filtrate was evaporated and the residue purified by chromatography eluting with DCM/diethylether (100: 0 then 80: 20 and then 0: 100) to give the title compound (5. 5g, 31percent) as a solid. NMR (DMSO-d6) : 8.15 (s, 1H), 8.62 (dd, 2H), 8. 99 (s, 1H).To a stirred solution pyrazin-2-ylmethanol (500 mg, 4.545 mmol) in DCM (20 ml) was added Dess-martin periodinane (2.89 g, 6.818 mmol) and stirred for 1 hr at RT. Reaction mass was diluted with DCM (100 ml) washed with saturated sodium bicarbonate solution (50 ml X 2) twice. DCM part was separated, dried over sodium sulfate, evaporated to dryness to get 300 mg crude, which was purified by column chromatography using 100-200 silica and 20percent EtOAc in hexane as eluent to afford pyrazine-2-carbaldehyde (100 mg) as brown liquid.Pyrazine carboxaldehyde, O-methyl oxime In a similar manner to that described in Example 7, but starting form pyrazine carboxaldehyde (J. Org. Chem. 37, 111 (1972)), the title compound was obtained in a 60percent yield m.p. 40°-41° C.pyrazine-2-carboxaldehyde After dissolving 2.50 ml of 2, 2, 6, 6-tetramethylpiperidine in 40 ml of tetrahydrofuran, the solution was cooled to -50° C. Next, 5.25 ml of n-butyllithium (2.6 M, n-hexane solution) was added dropwise thereto under a nitrogen atmosphere. The mixture was stirred for 25 minutes, cooled on ice, and stirred for an additional 35 minutes. It was then cooled to -78° C., and a solution of 1.89 g of 2-tert-butoxypyrazine [CAS No.70090-30-1] in tetrahydrofuran (5 ml) was added dropwise. After stirring the mixture for 15 minutes, 1.25 ml of N, N-dimethylformamide was added dropwise. After 10 minutes, water was added to the reaction solution and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in that order and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (1.00 g, 45percent, yield). 1H-NMR (400 MHz, CDCl3); delta (ppm) 1.68 (9H, s), 8.28 (1H, d, J=2.4 Hz), 8.30 (1H, d, J=2.4 Hz), 10.33 (1H, s).By the procedure of Example 2, using the following carboxaldehydes in place of 2-pyridinecarboxaldehyde:4-pyrimidinecarboxaldehyde2-By the procedure of Example 23, using in place of 2-pyridinecarboxaldehyde, the following carboxaldehydes:2-pyrimidinecarboxaldehyde2-pyrrolecarboxaldehyde2-EXAMPLE 112 7-[3-(Difluoromethyl)-1-piperazinyl]-1-ethyl-6, 8-difluoro-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acid A mixture of 3.54 g of pyrazine carboxaldehyde and 5.63 g of diethylaminosulfurtrifluoride were reacted as described by W. J. Middeton, J. of Chemistry, 40, 577 (1975). The product was purified by chromatography, then hydrogenated at 20 C. under 50 psi hydrogen with 0.58 g of platinum oxide in methanol for 4 hours. The product was collected and purified by chromatography, giving 100 mg of 3-difluoromethylpiperazine.A 3.54 g portion of 2-

Molecular Weight:108.10
XLogP3:-0.4
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:108.032362755
Monoisotopic Mass:108.032362755
Topological Polar Surface Area:42.8
Heavy Atom Count:8
Complexity:84.5
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes