Application of 109838-85-9,Some common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, molecular formula is C9H16N2O2, 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.
Example 1; (2S)-2- (fert-butoxycarbonyl) aminol-3-cLrcloheptylpropanoic acid building block; a) Methyl (2S)-2-amino-3-cycloheptylpropanoate; To a stirred solution of R-2,5-dihydro-3, 6-dimethoxy-2-isopropyl pyrazine (5 g, 27 mmol) in THF (80 mL) at-78 °C was added dropwise 2.5 M n-butyllithium in hexanes over 40 min, maintaining the temperature of the reaction mixture below-70 °C. To the reaction mixture was added dropwise a solution of iodomethylcycloheptane (Webb et al, J. Med. Chem. , 42,8 (1999), 1415-1421. ) (6.8 g, 28. 5 mmol) in THF (12 mL) over 50 min, maintaining the temperature of the reaction mixture below-70 °C. The reaction mixture was then stirred at 0 °C for another 75 min, acetic acid was added (2.45 mL) and stirring was continued for another 20 min. The reaction mixture was then diluted with ethyl acetate (200 mLI), washed with brine (2 x 50 mLI), dried (MgS04), filtered and concentrated in vacuo. Column chromatography of the residue using stepwise gradient elution (ethyl acetate in hexane 0-5percent) gave the pyrazine derivative as an oil (5.4 g, 68percent). A mixture of the pyrazine derivative (5.4 g, 18.5 mmol) in acetonitrile (55 mL), water (45 mL) and 1 M aqueous hydrochloric acid (45 mL) was stirred at room temperature for 2 h, then concentrated in vacuo to approximately half the volume. Aqueous NaHCO3 (1 M) was added until just alkaline, then the reaction was extracted with dichloromethane (3 x 50 mL). The extracts were dried (MgSO4), filtered and concentrated in vacuo onto silica. Column chromatography of the residue using stepwise gradient elution (ethyl acetate in hexane and triethylamine (0.5percent) 20-100percent) gave pure fractions of (8) which were concentrated in vacuo to a syrup (2.14 g, 58percent). Additional material could be obtained by repeated chromatography.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, its application will become more common.
Reference:
Patent; MEDIVIR UK LTD; PEPTIMMUNE, INC; WO2005/82876; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem