A new synthetic route of 109838-85-9

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.

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. COA of Formula: C9H16N2O2

DMSO (1.95 g, 1.64 mL, 25.0 mmol) was added dropwise to a solution of oxalyl chloride (1.52 g,1.05 mL, 12.0 mmol) in CH2Cl2 at -78 0C. After stirring at -78 0C for 15 min, 4-phenyl-l-butanol (1.50 g, 1.52 mL, 10.0 mmol) was added dropwise. After 15 min, triethylamine (5.05 g, 6.96 mL) was added dropwise. After warming to r.t. over 2 hours, water (50 mL) was added and the solution was extracted with CH2Cl2 (4 X 50 mL). The combined organic phase was washed with HCl (0.25 N, 3 X 50 mL), water (50 mL), saturated NaHCO3, and brine. The organic extract was dried over Na2SO4, concentrated, and passed through a short silica column (2 x 3 cm), eluted with CH2Cl2. Solvent was removed to give 4-phenylbutanal as a colorless oil (1.30 g, 87percent). 1H NMR (500 MHz, CDCl3) delta 9.76 (t, / = 1.5 Hz, 1 H), 7.31-7.27 (m, 2 H), 7.22-7.17 (m, 2 H), 2.67 (t, / = 7.5 Hz, 2 H), 2.46 (dt, J = 1.6, 7.32 Hz, 2 H), 1.97 (m, 2 H).[000199] To a solution of the bislactim (R)-2-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (1.842 g, 1.792 mL, 10.0 mmol) in THF (20 mL) at -78 0C was slowly added n-BuLi (6.875 mL, 1.6 M in hexanes, 11.0 mmol) under Ar. After stirring at -78 0C for 20 min, A methyl iodide solution (1.562 g, 0.686 mL, 11.0 mmol) in THF (5 mL) was added. It was stirred at -78 0C for 2 h. A further portion of n-BuLi (6.25 mL, 1.6 M in hexanes, 10.0 mmol) was added at -78 0C and the solution was warmed to 0 0C. A solution of SnCl2 (1.0 g, 5.3 mmol) in THF (20 mL) was added and stirred at 0 0C for 15 min. After cooling to -78 0C, a 4-phenylbutanal solution (0.74 g, 5.0 mmol) was added. After the mixture was stirred at -78 0C for 3 h, it was warmed to r.t. and a phosphate buffer (pH 7.0, 0.10 M, 150 mL) was added with stirring for an additional 10 min. The mixture was filtered and the solid washed with ether. The aqueous phase was extracted with ether (3 X 50 mL) and the combined organic phase was washed with brine and dried over Na2SO4. Solvent was removed and the residue was purified by silica gel column chromatography (3 X 25 cm, hexanes: EtOAc 9:1) to give compound 65 as a colorless viscous oil (850mg, 49percent). 1H NMR (500 MHz, CDCl3) delta 7.28-7.25 (m, 2 H), 7.19-7.15 (m, 3 H), 3.94 (d, / = 3.5 Hz, 1 H), 3.70 (s, 3 H), 3.64 (s, 3 H), 3.59 (dt, J = 2.0, 10.3 Hz, IH), 2.66-2.60 (m, 2 H), 2.28-2.25 (m, 1 H), 1.99 (d, J = 10.0 Hz, 1 H), 1.95-1.85 (m, I H), 1.75-1.65 (m, I H), 1.60-1.52 (m, 1 H), 1.35 (s, I H), 1.33-1.23 (m, 1 H), 1.08 (d, / = 7.0 Hz, 3 H), 0.69 (d, / = 6.9 Hz, 1 H). ESIMS (MNa+) m/z 369.4.[000200] Compound 65 (692 mg, 2.0 mmol) is dissolved in acetonitrile (24 mL) containing HCl (0.50 M, 24 mL). After the mixture is stirred at r.t. for 12 h, the solvent is removed, the residue is dissolved in a NaOH solution (2.0 M, 20 mL) in MeOH (2OmL), and the progress of the reaction is monitored by TLC. The reaction mixture was neutralized with a solution of HOAc, and solvent is removed. The residue is purified by reverse phase HPLC to give desired product, compound 66, as an amorphous white solid.

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; FORBES MEDI-TECH (RESEARCH), INC.; WO2008/31032; (2008); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem