Category: 622392-04-5

These common heterocyclic compound, 622392-04-5, name is 2-Bromo-5-iodopyrazine, 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. category: Pyrazines

2-Bromo-5-iodopyrazine [CAS RN: 622392-04-5] (3.50 g, 12.3 mmol, 1.0 eq),4,4,5,5-tetramethyl-2-(prop-1 -en-2-yl)-1 ,3,2-dioxaborolane [CAS RN: 126726-62-3] (3.10 g, 18.4 mmo[, 1.5 eq), Pd(dppf)C[2.CH2C[2 (502 mg, 0.61 mmo[, 0.05 eq) and cesium carbonate (12.0 g, 36.9 mmo[, 3.0 eq) were dissolved in 130 mL dioxane/water (5/1). The reaction mixture was heated to 90C for 2 h. On cooling, the reaction mixture was partitioned between water anddichloromethane. The organic phase was washed with brine and the phases were separated by the use of a Whatman filter. The volatile components were removed in vacuo and the crude material was purified via preparative MPLC (Biotage Isolera; 100 g SNAP cartridge: hexane -> hexane/ethyl acetate 9/1) to give 600 mg (25% yield of theory) of the title compound in a round 50% purity(UPLC-area%). The impurity was identified as 2,5-di(prop-1-en-2-yl)pyrazine, that was not expected to interfere in the subsequent reaction step. The material obtained was used without further purification.UPLC-MS (Method 4): R = 1.18 mm; MS (ESI0): m/z = 199 [M].

The synthetic route of 2-Bromo-5-iodopyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BAeRFACKER, Lars; SIEMEISTER, Gerhard; HEINRICH, Tobias; PRECHTL, Stefan; STOeCKIGT, Detlef; ROTTMANN, Antje; WO2015/113927; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 622392-04-5, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 622392-04-5 as follows.

a) 2-Bromo-5- (4- [ 1 ,2,4] triazol- 1 -yl-but- 1 -ynyl)-pyrazine A mixture of 2.00 g (7.0 mmol) 2-bromo-5-iodo-pyrazine, 1.02 g (8.4 mmol) 1- but-3-ynyl- IH-[1, 2,4] triazole, 9.95 g (98.3 mmol) triethylamine, 147 mg (0.8 mmol) copper (I) iodide and 404 mg (0.3 mmol) tetrakis(triphenylphophine) palladium (0) in 30 ml DMF were stirred at room temperature overnight. After addition of 80 ml dichloromethane and 100 ml 0.5N HCl the phases were separated and the organic layer was dried over Na2SCv Column chromatography (silica, ethyl acetaterheptane 0:1 to 1:1) returned 0.90 g (46%) 2-bromo-5-(4-[ 1,2,4] triazol- 1-yl- but-l-ynyl)-pyrazine as a yellow solid. MS: M = 278.0 (ES+) 1H-NMR (400 MHz, D.-DMSO): delta= 3.08 (t, 6.5 Hz, 2H), 4.47 (t, 6.5 Hz, 2H), 8.02 (s, IH), 8.49 (s, IH), 8.62 (s, IH), 8.82 (s, IH).

According to the analysis of related databases, 622392-04-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2007/39226; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 622392-04-5, These common heterocyclic compound, 622392-04-5, name is 2-Bromo-5-iodopyrazine, 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.

Preparation 67: iert-Butyl (2S)-2-{4-[4-(5-bromopyrazin-2-yl)phenyl]-1 H-imidazol-2-yl}pyrrolidine-1- carboxylateMethod A:Potassium phosphate (7.39 g, 34.81 mmol) was added to a stirred solution of 2-bromo-5-iodopyrazine obtained from Preparation 10 (7.65 g, 17.41 mmol) and tert-butyl (2S)-2-{4-[4-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)phenyl]-1 H-imidazol-2-yl}pyrrolidine-1 -carboxylate obtained from Preparation 3 (6.45 g, 22.63 mmol) in a mixture of 1 ,4-dioxane : water (3:7, 500 mL). The mixture was degassed for 20 minutes after which time tetrakis(triphenylphosphine)palladium (0) (2.00 g, 1 .74 mmol) was added and the reaction heated to 90C for 2 hours. After this time, the reaction mixture was cooled to room temperature and poured into a saturated solution of sodium bicarbonate (500 mL). The product was extracted with ethyl acetate (3 x 500 mL). The combined organic layers were dried over sodium sulphate and the solvent was removed under reduced pressure to a brown crude oil. The crude product was purified by flash chromatography (ethyl acetate:dichloromethane, 50 : 50 to 100 : 0) to give the title compound as a pale yellow solid (5.56 g).LCMS: (run time = 4.5 minutes, System J): Rt = 2.22 minutes; m/z 470.19 and 472.07 [MH+]H NMR (400 MHz, CD3OD) delta = 8.95 (s, 1 H), 8.75 (s, 1 H), 8.1 (d, 2H), 7.85 (d, 2H), 7.50-7.40 (m, 1 H), 4.90- 4.80 (m, 1 H), 3.75-3.65 (m, 1 H), 3.55-3.45 (m, 1 H), 2.40-2.30 (br. m, 1 H), 2.10-1.90 (m, 3H), 1.25 (s, 9H)

The synthetic route of 622392-04-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER LIMITED; MILBANK, Jared Bruce John; TRAN, Thien Duc; WAKENHUT, Florian; WO2011/154871; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 622392-04-5, name is 2-Bromo-5-iodopyrazine, A new synthetic method of this compound is introduced below., Application In Synthesis of 2-Bromo-5-iodopyrazine

Intermediate 31 (200 mg, 0.602 mmol), 2-bromo-5-iodopyrazine (172 mg, 0.602 mmol), 2M aqueous sodium carbonate solution (0.903 mL, 1.807 mmol) and anhydrous DMSO (2 mL) were charged to a sealed tube. The mixture was degassed by bubbling30 with nitrogen for 5 minutes before the addition of tetrakis(triphenylphosphine)palladium(0) (35 mg, 0.03 mmol). The mixture was sealed under nitrogen, then stirred at100C for 1 h. The reaction mixture was partitioned between water (25 mL) and EtOAc(50 mL), then the organic phase was washed with saturated aqueous NaHCO3 solution(10 mL) and brine (10 mL), dried over sodium sulfate and concentrated under vacuum. The residue was purified by FCC, eluting with a gradient of 17-100% EtOAc in heptane, to afford the title compound (160 mg, 42%) as an off white solid. oH (500 MHz, CDC13) 8.72-8.68 (m, 2H), 7.93 (s, 2H), 7.33-7.26 (m, 2H), 7.18 (d, J8.0 Hz, 1H), 7.13 (t, J7.55 Hz, 1H), 7.01 (t, J8.3 Hz, 1H), 6.82-6.52 (t, 1H), 4.36 (s, 2H), 2.61 (s, 3H).

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:
Patent; UCB PHARMA S.A.; BENTLEY, Jonathan Mark; BROOKINGS, Daniel Christopher; BROWN, Julien Alistair; CAIN, Thomas Paul; CHOVATIA, Praful Tulshi; FOLEY, Anne Marie; GALLIMORE, Ellen Olivia; GLEAVE, Laura Jane; HEIFETZ, Alexander; HORSLEY, Helen Tracey; HUTCHINGS, Martin Clive; JACKSON, Victoria Elizabeth; JOHNSON, James Andrew; JOHNSTONE, Craig; KROEPLIEN, Boris; LECOMTE, Fabien Claude; LEIGH, Deborah; LOWE, Martin Alexander; MADDEN, James; PORTER, John Robert; QUINCEY, Joanna Rachel; REED, Laura Claire; REUBERSON, James Thomas; RICHARDSON, Anthony John; RICHARDSON, Sarah Emily; SELBY, Matthew Duncan; SHAW, Michael Alan; ZHU, Zhaoning; WO2014/9295; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 622392-04-5, name is 2-Bromo-5-iodopyrazine, molecular formula is C4H2BrIN2, 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: C4H2BrIN2

t-butyl 4-(hydroxymethyl)piperidin-1-carboxylate (the product of synthesis step 1 of compound 431; 2.70 g, 12.54 mmol), 2-bromo-5-iodopyrazine (3.57 g, 12.54 mmol) and NaH (0.36 g, 15.05 mmol) were dissolved in 70 C. for THF (30 mL), following with stirring at the same temperature for 6 hours. The reaction mixture was added with water, and extracted with EtOAc. The organic layer was washed with saturated NH4Cl aqueous solution, dried over anhydrous MgSO4, and filtered. The filtrate was concentrated under reduced pressure. The concentrate was purified by column chromatography (SiO2, 12 g cartridge; EtOAchexane=0% to 20%), and concentrated to yield the title compound as white solid (4.04 g, 76%)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 622392-04-5, its application will become more common.

Reference:
Patent; CHONG KUN DANG PHARMACEUTICAL CORP.; Lee, ChangSik; Jang, TaegSu; Choi, DaeKyu; Ko, MooSung; Kim, DoHoon; Kim, SoYoung; Min, JaeKi; Kim, WooSik; Lim, YoungTae; US2015/166480; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem