Some common heterocyclic compound, 19745-07-4, name is 2,5-Dichloropyrazine, molecular formula is C4H2Cl2N2, 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. category: Pyrazines
Preparation of (l^S^^^-methyl 3-amino-5-(5-(( )-2-(5-chloropyrazin-2-yl)-2- fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-l- carboxylate (Example 149). 1 ) A solution of 3-((tert-butoxycarbonyl)((2-(trimethylsilyl)ethoxy) methyl)amino)-5-(2-fluoro-5-((i-2-fluoro-2-(tributylstannyl)vinyl)phenyl)-5-methyl-2-thia- 4-azabicyclo[4.1.0]hept-3-ene-l-carboxylate (20B) (80 mg, 0.093 mmol) in 0.5 mL of DMF was added dropwise to a mixture of 2,5-dichloropyrazine (62.5 mg, 0.420 mmol), bis(di-fert- butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(ii) (6.60 mg, 9.33 muiotaetaomicron) and copper(i) iodide (18 mg, 0.093 mmol) in 0.5 mL of DMF. After 1 hour, the mixture was directly loaded onto a flash column (DCM to DCM/EA = 20: 1) to give (lS,5S,6S)-methyl 3- ((teri-butoxycarbonyl)((2-(trimethylsilyl)ethoxy)methyl)amino)-5-(5-((Z)-2-(5- chloropyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5 -methyl -2 -thia-4-azabicyclo [4.1.0]hept- 3-ene-l-carboxylate (22 mg, 35percent yield) as a gum. To neat ( 3-((teri-butoxycarbonyl)((2- (trimethylsilyl)ethoxy)methyl)amino)-5-(5-((Z)-2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2- fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-l-carboxylate (22 mg, 0.032 mmol) was added 0.2 mL of 96percent sulfuric acid. After stirring for 10 minutes (mix thoroughly), the reaction was quenched with sat. NaHCC>3 to pH = 8 and was extracted with DCM three times. The combined organic phases was dried over sodium sulfate, and concentrated. Flash chromatography (S1O2, DCM/EtOAc = 10: 1 to 4: 1 to 2: 1) gave (15′,55′,6S)-methyl 3-amino-5-(5-((Z)-2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2- fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-l-carboxylate (Example 149) (13 mg, 0.029 mmol, 89 percent yield) as a white solid. MS m/z = 451 (M+H). l NMR (300 MHz, CDCI3) delta 8.65 (s, 1H), 8.56 (s, 1H), 7.99 (d, J=7.45 Hz, 1H), 7.64-7.81 (m, 1H), 7.00- 7.20 (m, 2H), 3.81 (s, 3H), 2.58 (t, J=8.62 Hz, 1H), 1.77 (s, 3H), 1.57 (dd, J=4.82, 9.50 Hz, 1H), 1.10-1.21 (m, 1H).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 19745-07-4, its application will become more common.
Reference:
Patent; AMGEN INC.; ALLEN, Jennifer, R.; AMEGADZIE, Albert; BOURBEAU, Matthew, P.; BROWN, James, A.; CHEN, Ning; FROHN, Michael, J.; LIU, Longbin; LIU, Qingyian; PETTUS, Liping, H.; QIAN, Wenyuan; REEVES, Corey, M.; SIEGMUND, Aaron, C.; (509 pag.)WO2017/24180; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem