Application of 4949-13-7, A common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, molecular formula is C4H3FN2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
General procedure: (R)-4-N-Boc-2-methylpiperazine (665 mg, 3.32 mmol), 1-adamantoyl chloride (990 mg, 4.98 mmol), and DIEA (1.15 mL, 6.64 mmol) were dissolved in 2.0 mL of dichloromethane, and the reaction was monitored by LCMS. Upon completion, 5.0 mL of MeOH was added, and the mixture was concentrated in vacuo. The residue was purified by flash chromatography. The purified product was immediately dissolved in 1.0 mL of MeOH and excess 4 N HCl in dioxanes (4.0 mL, 16 mmol). Once the protecting group had cleaved as judged by LCMS, an aqueous solution of saturated sodium bicarbonate was added until the pH was basic. The mixture was extracted with dichloromethane, and the organic layers were concentrated in vacuo to afford 814 mg (94% yield) of adamantan-1-yl((R)-2-methylpiperazin-1-yl)methanone as a white solid. Adamantan-1-yl((R)-2-methylpiperazin-1-yl)methanone (355 mg, 1.35 mmol) and 2-cyano-3-fluoropyridine (1.42 mL, 5.41 mmol) were dissolved in 4.0 mL of NMP in a microwave reaction vial and heated in the microwave for 10 min at 250 C. The reaction mixture was purified via reverse phase chromatography (0.1% TFA in H2O/MeCN). The fractions containing the product were combined and neutralized by the addition of aqueous saturated sodium bicarbonate. The mixture was extracted with dichloromethane, and the organic layers were combined and concentrated in vacuo. The residue was dissolved in 1.0 mL of MeOH and 4 N HCl in dioxanes (3.0 mL, 12 mmol) and stirred for 2 h. The mixture was concentrated in vacuo to afford 212 mgs (39% yield) of the HCl salt as a yellow solid.
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Article; Lovell, Kimberly M.; Felts, Andrew S.; Rodriguez, Alice L.; Venable, Daryl F.; Cho, Hyekyung P.; Morrison, Ryan D.; Byers, Frank W.; Daniels, J. Scott; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A.; Bioorganic and Medicinal Chemistry Letters; vol. 23; 13; (2013); p. 3713 – 3718;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem