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. Computed Properties of C9H16N2O2
General procedure: n-Butyllithum (500 muL, 1.6 M in hexane) was added dropwise to a stirred solution of (2R)-2,5 -dihydro-2-isopropyl-3,6-dimethoxypyrazine( 150 jiL, 0.83 mmol) in 3 mL dry THF at -78°C under argon atmosphere. The resultant mixture was allowed to be stirred for additional 5 mm. The obtained yellow solution was subsequently transferred via a double-tipped needle to stirred slurry of copper (I) cyanide (38 mg, 0.42 mmol) in 2 mL THF at -78°C under argon. This mixture was stirred at 0 °C for around 1.5 mm to afford cyanocuprate as a tan colored solution. The reaction was then immediately cooled down to-78 °C. A solution of the iodide 6 (0.28 mmol) in 10 mL dry THF was then added dropwise. The reaction mixture was stirred at -78 °C for 30 mm and then for 16 h at -25 °C under argon. The reaction was quenched by adding a 1:9 mixture of aqueous ammonia/saturated aqueous ammonium chloride (15 mL). The aqueous phase was further extracted with diethyl ether (3 x20 mL). The organic layer was combined and then washed with the 1:9 mixtures of concentrated aqueous ammonia/saturated aqueous ammonium chloride, followed by brine, and then dried with anhydrous Na2SO4. After removing the volatile components with rotavapor, the crude product was purified by silica gel flash chromatography (hexane:EtOAc = 4:1 then 3:1) afforded the desired product 7 as colorless oil. [0066] 7b R = Et, 79percent yield. [CL]D179 +6.75(c 1.01, CHC13); 1H-NMR (600 MHz, DMSO-d6,64°C): delta 0.65(d, 3H,J= 6.8 Hz), 0.99(d, 3H,J= 6.8 Hz), 1.10(t, 3H,J= 7.0 Hz), 1.25(s,3H), 1.37(s, 3H), 1.45-1.48(m, 1H), 1.50-1.60(m, 3H), 1.71-1.75(m, 1H), 1.82-1.85(m, 1H),2.15-2.20(m, 1H), 3.14-3.19(m, 2H), 3.25(s, 3H), 3.60(s, 3H), 3.61(s, 3H), 3.89(t, 1H, J 3.6Hz), 3.98(dd, 1H, J= 10.8Hz, 4.0 Hz), 3.99-4.01(m, 2H), 4.53(d, 1H, J 5.9 Hz), 4.55(d, 1H,J= 5.9 Hz), 4.86(s, 1H), 5.09(s, 2H), 7.30-7.31(m, 1H), 7.33-7.36(m, 4H); 13C-NMR (150MHz, DMSO-d6 rotamers): delta 14.20, 15.17, 16.38, 19.01, 24.64, 26.23, 27.90, 30.73, 31.03,37.52, 37.88, 52.07, 53.83, 54.03, 54.27, 59.77, 65.81, 66.13, 83.29, 83.41, 83.66, 83.70,84.90, 109.05, 109.22, 111.32, 127.22, 127.60, 127.68, 128.21, 128.36, 136.97, 137.26,155.52, 162.76, 163.03, 163.11; MS(ESI) mlz: 590 [M+H] HRMS: calculated forC31H48N308 ([M+H]+) 590.3441, found 590.3440.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 109838-85-9, its application will become more common.
Reference:
Patent; MEMORIAL SLOAN-KETTERING CANCER CENTER; ZHENG, Weihong; LUO, Minkui; IBANEZ SANCHEZ, Glorymar del Valle; WO2013/63417; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem