2,6-Dimethoxypyrazine

6-Dimethoxypyrazine (V): A mixture of 1, 6-dichloropiρerazine U (3.9g; 26 mmol) and freshly prepared sodium methoxide (62 mmol) in anhydrous methanol (50 ml) was refluxed overnight and the solvent was removed under reduced pressure. The residue was diluted to 100 ml with CHthe molar ratio of Sodiummethoxide and dibromopyrazine is 5:1 placed into three-necked flask with astirrer and a thermometer, added 500ml of Distilled water, start the mixer andwith speed of 200r / min it was stirredfor 10min; After the mixing the mixture was placed at reflux apparatus , heatedup to 60 C, refluxed for 2h, , the collected reflux liquid was put into abeaker then placed in an ice-water bath , at 4 C under ice the precipitatewas allowed to stand for 2h, filtered toobtain precipitate and spare after rotary evaporation drying; The massconcentration of concentrated sulfuric acid is 98% and after drying as mentioned above the precipitatemass ratio is 12: 1 were mixed andtogether poured into a beaker of 500mL, after stirred with a glass rod for10min placed on the shaker and Oscillating reaction for 2 h , then againadded 50mL of nitric acid solution with a mass concentration of 95% , continues to oscillate the reaction for 20minto obtain a mixed solution; The ratio of the mixed liquid and ammonia water is1:5, the ammonia water was poured into the above mentioned mixed solution, placedthe reaction solution on a magnetic stirrer, with speed of 600r / min it was stirred for 10s , afterwards reduce speed to200r / min and continue to stir for 30min. After completion of the stirring, 400ml of anhydrous ethanol added into the mixture solution, placed intoultrasonic vibration device, ultrasonic vibration reaction for 1h, thentransferred to a distillation apparatus, heated to 60 C, ethanol was removedby distillation, for drying used vacuum freeze-drying machine and after crushingof solid particles; Take 1g of the above mentioned solid particles and put into100ml of beaker , added 15ml of glacial acetic acid and 10ml of hydrogenperoxide with a mass concentration of 30%, water bath warmed to 40 C, andafter the 6hrs of reaction filtrated to obtain precipitate and dried to obtain 2, 6-diamino-3, 5-dinitro-1-oxidepyrazine.General procedure: Representative procedure for the preparation of 1-phenoxycarbonyl-2-phenyl-3-methoxy-1, 2-dihydropyrazine (3a). To a stirred solution of 2-methoxypyrazine (0.200 g, 1.816 mmol) inanhydrous THF (5 mL) was added phenylchloroformate (0.28 mL, 2.225 mmol) at 0 C andstirring was continued under nitrogen atmosphere until salt formation was completed (15 min, asdetermined by TLC on neutral alumina, EtOAc/hexanes 1:19). The reaction mixture was cooledto -41 C, a 1 M solution of phenylmagnesium bromide in THF (2.4 mL, 2.4 mmol) was addedand the mixture stirred until reaction completion (40 min, as determined by TLC on neutral SiO2, EtOAc/hexanes 1:9), and then quenched with 2 mL of aqueous 20% NH4OH/NH4Cl 1:1 (w/w).The mixture was extracted with dichloromethane (2 × 15 mL), dried over Na2SO4, andconcentrated in vacuo. Purification of the crude mixture by flash silica gel columnchromatography (0-15% EtOAc/hexanes) afforded 3a (0.488 g, 87%) as a white solid (3:2mixture of rotamers): mp: 81-82 C; 1H NMR (CDCl3, 500 MHz) delta 7.49-7.27 (m, 7H), 7.20 (t, J= 7.5 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 6.99 (d, J = 7.5 Hz, 1H), 6.67 and 6.63 (2d due torotamers, J = 5.5 Hz, 1H), 6.16 and 6.14 (2d due to rotamers, J = 5.0 Hz, 1H), 5.89 and 5.87 (2sdue to rotamers, 1H), 3.84 and 3.83 (2s due to rotamers, 3H); 13C NMR (CDCl3, 125 MHz) delta160.2, 160.0, 151.6, 151.5, 150.7, 150.4, 136.8, 135.9, 129.3, 128.8, 128.7, 128.6, 127.2, 126.6, 125.9, 125.8, 121.3, 118.2, 118.1, 112.5, 111.8, 56.0, 54.6, 54.0, 53.9; HRMS (ESI) m/z calcdfor C18H17N2O3 [M + H]+ 309.12337, found 309.123554General procedure: A magnetically stirred solution of xanthate (2.0 equiv) and pyrazine (1.0 equiv) in 1, 2-dichloroethane (1.0mmol/mL according to the xanthate) was refluxed for 15min under a flow of nitrogen. Then dilauroyl peroxide (DLP) was added portionwise (20mol % according to the xanthate) every hour until total consumption of one substrate. The reaction mixture was then cooled to room temperature and the solvent was evaporated under reduced pressure. Unless otherwise specified, the crude product was purified by flash chromatography on silica gel.General procedure: A magnetically stirred solution of xanthate (2.0 equiv) and pyrazine (1.0 equiv) in 1, 2-dichloroethane (1.0mmol/mL according to the xanthate) was refluxed for 15min under a flow of nitrogen. Then dilauroyl peroxide (DLP) was added portionwise (20mol % according to the xanthate) every hour until total consumption of one substrate. The reaction mixture was then cooled to room temperature and the solvent was evaporated under reduced pressure. Unless otherwise specified, the crude product was purified by flash chromatography on silica gel.20 ml of 30% hydrogen peroxide was slowly added to 20 ml of acetic acid at room temperature, and then 4 g of , 6-Dimethoxypyrazine (V): A mixture of 1, 6-dichloropirhoerazine U (3.9g; 26 mmol) and freshly prepared sodium methoxide (62 mmol) in anhydrous methanol (50 ml) was refluxed overnight and the solvent was removed under reduced pressure. The residue was diluted to 100 ml with CH2Cl2 and the solution washed with water, brine and dried over anhydrous MgSO4 and filtered off. The filtrate was evaporated under reduced pressure to

Used as pharmaceutical intermediate

Molecular Weight:140.14
XLogP3:1.6
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:140.058577502
Monoisotopic Mass:140.058577502
Topological Polar Surface Area:44.2
Heavy Atom Count:10
Complexity:89.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes