Pyrazines

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. 24241-18-7, name is 2-Amino-3,5-dibromopyrazine, A new synthetic method of this compound is introduced below., HPLC of Formula: C4H3Br2N3

3,5-Dibromopyrazin-2-amine (200 mg, 0.79 mmol) and chloroacetaldehyde (200 mul, 1.58 mmol) were dissolved in DMF (5 ml). The mixture was stirred at 100 C. overnight. LC/MS showed 6,8-dibromoimidazo[1,2-a]pyrazine plus the mass with one bromine displaced by chlorine. The crude material was used for the next step without further purification. 1H NMR (400 MHz, CDCl3) delta 8.28 (s, 1H) 7.88 (s, 1H) 7.80 (s, 1H). [M+H] calc’d for C6H3Br2N3, 276; found, 276.

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; Dong, Qing; Hosfield, David J.; Paraselli, Bheema R.; Scorah, Nicholas; Stafford, Jeffrey A.; Wallace, Michael B.; Zhang, Zhiyuan; US2006/84650; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 6164-79-0, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 6164-79-0, name is Methyl 2-pyrazinecarboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

[0537] Synthesis of pyrazin-2-ylmethanol: [0538] To a stirred solution of methyl pyrazine-2-carboxylate (0.5 g, 3.62 mmol) in H20 (10 mL) was added NaBH4 (685 g, 18.02 mmol) portion wise at 0 C, and the reaction mixture was allowed to warm to RT and stirred for 30 min under inert atmosphere. To this saturated K2C03 (10 mL) and EtOH (5 mL) was added and stirring was continued for another 1 h at RT. The progress of the reaction was monitored by TLC; the reaction mixture was extracted with EtOAc. The combined organic layer was dried over sodium sulphate, filtered and concentrated in vacuo to afford crude pyrazin-2-ylmethanol (0.3 g). LC-MS: 99.91%; 111.9 (M++l) (column; X-bridge C-18, (50×3.0 mm, 3.5mu); RT 0.72 min. 0.1% TFA in water: ACN; 0.8 ml/min); TLC: 100% EtOAc (Rf: 0.2).

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

Reference:
Patent; ENVIVO PHARMACEUTICALS, INC.; RIPKA, Amy; SHAPIRO, Gideon; MCRINER, Andrew, J.; BURSAVICH, Matthew, Gregory; WO2013/142269; (2013); A1;,
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Synthetic Route of 143591-61-1, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 143591-61-1, name is 3-Bromo-8-chloroimidazo[1,2-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows.

Intermediate Example 7-1 : Preparation of 3-bromo-N-(2- methylpropyl)imidazo[ 1 ,2-a]pyrazin-8-amineTo a stirred solution of 3-bromo-8-chloro-imidazo[1 ,2-a]pyrazine which was prepared according to intermediate example 2-1 (4 g, 17.2 mmol) in THF (54 mL) was added 4.9 mL isobutylamine (3.77 g, 51.6 mmol, 3 eq) and 7.2 mL TEA (5.22 g, 51.6 mmol, 3 eq) in one portion at rt and the mixture was heated at 140C in a microwave tube. Purification by flash chromatography yielded 4.45 g (91 %) of the title compound. 1H-NMR (300 MHz, d6-DMSO): delta = 7.64 (d, 1 H), 7.61 (s, 1 H), 7.48 (d, 1 H), 7.36 (d, 1 H), 3.24 (dd, 2H), 1.96 (m, 1 H), 0.85 (d, 6H) ppm. UPLC-MS: RT = 0.84 min; m/z 270.2 [MH+]; required MW = 269.2.

The chemical industry reduces the impact on the environment during synthesis 3-Bromo-8-chloroimidazo[1,2-a]pyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; KOPPITZ, Marcus; KLAR, Ulrich; JAUTELAT, Rolf; KOSEMUND, Dirk; BOHLMANN, Rolf; BADER, Benjamin; LIENAU, Philip; SIEMEISTER, Gerhard; WO2012/80229; (2012); A1;,
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Reference of 13924-94-2, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 13924-94-2, name is Methyl 5-aminopyrazine-2-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Methyl 5-aminopyrazine-2-carboxylate (8) (0.650g, 4.2483mmol) was reacted with excess of acetic anhydride (5mL) and heated at 90C for 2h. The reaction mixture was evaporated and partitioned between saturated NaHCO3 solution and ethyl acetate. Organic layer was evaporated to get 0.345g of compound 9a as pale yellow solid (yield 41.6%). 1H NMR (400MHz, DMSO-d6) delta 11.29 (s, 1H), 9.41 (d, J=1.4Hz, 1H), 8.96 (d, J=1.4Hz, 1H), 2.18 (s, 3H), 1.81 (s, 3H). C8H9N3O3 [M]: 195.18; MS (ESI) m/z: [M+H]+: 196.05 [M-H]+, 194.05

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, Methyl 5-aminopyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Trivedi, Prakruti; Adhikari, Nilanjan; Amin, Sk. Abdul; Jha, Tarun; Ghosh, Balaram; European Journal of Pharmaceutical Sciences; vol. 124; (2018); p. 165 – 181;,
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117719-17-2, name is 5-Bromo-3-morpholinopyrazin-2-amine, belongs to pyrazines compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. name: 5-Bromo-3-morpholinopyrazin-2-amine

Chloroacetaldehyde (4.4 g) was mixed with isopropanol (15 mL) and a portion of the mixture (10 mL) was added to a round bottom flask containing compound 2 (1.7 g). Then the temperature was raised to 45 C and stirring was continued. After 1 h, the remaining solution was added and thetemperature raised to 65 C with continuous stirring. After TLC indicated the reaction was finished, the reaction was stopped and cooled to room temperature. Then the solution was added into a beaker containing ice water (300 mL) with continuous stirring. The brown-yellow solid that precipitated was filtered and dried to give the product in a yield of 26.8%. 1H-NMR (DMSO-d6) delta 7.93 (s, 1H),7.25 (d, J = 7.3 Hz, 1H), 7.01 (d, J = 7.3 Hz, 1H), 3.45 (s, 4H), 3.77 (d, J = 4.3 Hz, 4H).

The synthetic route of 117719-17-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Xu, Shan; Sun, Chengyu; Chen, Chen; Zheng, Pengwu; Zhou, Yong; Zhou, Hongying; Zhu, Wufu; Molecules; vol. 22; 2; (2017);,
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875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, belongs to pyrazines compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. HPLC of Formula: C6H4BrN3

To a solution of I-69 (300 mg, 0.6 mmol) in DMF (10 mL) are added I-87 (140 mg, 0.7 mmol), tetrakis(triphenylphosphine)palladium (0) (70 mg, 0.06 mmol) and 2M Na2CO3 (1.5 mL, 3.0 mmol). The mixture is heated to 100 C. for 1 hour in a microwave reactor. The mixture is cooled down and is extracted with H2O (20 mL) and EtOAc (30 mL). The combined organic layer is dried with MgSO4 and is filtered. The filtrate is concentrated and the residue is purified by silica gel flash column chromatography with 10% MeOH in CH2Cl2 as the eluent to afford the title compound (200 mg). Example 176-180, Table 1-the reaction is run at 120 C.Example 176-180, Table 1-the reaction is run at 120 C. [0509] Example 184-185, Table 1-the reaction is run at 120 C Example 191, Table 1-the reaction is run at 120 C. Example 239-243, Table 1-the reaction is run for 6 hours at 100 C. in an oil bath

The synthetic route of 875781-43-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Boehringer Ingelheim International GmbH; BYLOCK, Lars Anders; US2013/195879; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. name: (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

To a 500 mL flame dried flask was added (i?)-2-isopropyl-3, 6- dimethoxy-2,5-dihydropyrazine (10.0 g, 54.3 mmol) and anhydrous THF (200 mL). The solution was cooled to -78 °C. “-BuLi (2.5M in hexane, 24.0 mL, 59.7 mmol) was added dropwise. After the solution was allowed to stir at -78 °C for 30 minutes, Compound Int-16b (in 5 mL anhydrous THF) was added dropwise. After the solution was allowed to stir at -78 °C for 1 hour, it was allowed to warm up to room temperature in two hours. Water (100 mL) and Et20 (150 mL) were added. The organic layer was separated and the aqueous layer was extracted with Et20 (100 mL) twice. The organic layers were combined, washed with brine, dried over Na2S04, filtered and concentrated in vacuo. The residue obtained was purified using Si02 chromatography (40 g, eluted with Et20 in Hexane: 0percent to 3percent) to provide Compound Int-16c (10.43 g, 58.0percent).

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; MERCK SHARP & DOHME CORP.; KOZLOWSKI, Joseph A.; ROSENBLUM, Stuart B.; COBURN, Craig A.; SHANKAR, Bandarpalle, B.; ANILKUMAR, G., Nair; CHEN, Lei; DWYER, Michael, P.; JIANG, Yueheng; KEERTIKAR, Kartik, M.; LAVEY, Brian, J.; SELYUTIN, Oleg, B.; TONG, Ling; WONG, Michael; YANG, De-Yi; YU, Wensheng; ZHOU, Guowei; WU, Hao; HU, Bin; ZHONG, Bin; SUN, Fei; JI, Tao; SHEN, Changmao; RIZVI, Razia; ZENG, Qingbei; WO2012/41014; (2012); A1;,
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Pyrazine | C4H4N2 – PubChem

Reference of 1379338-74-5, The chemical industry reduces the impact on the environment during synthesis 1379338-74-5, name is 5,7-Dichloropyrido[3,4-b]pyrazine, I believe this compound will play a more active role in future production and life.

Intermediate 22: 1,1-Dimethylethyl (2R)-2-{[(7-chloropyrido[3,4-b]pyrazin-5-yl)amino]methyl}-4-morpholinecarboxylate 1,1-dimethylethyl (2R)-2-(aminomethyl)-4-morpholinecarboxylate (for preparation see: J. Medicinal Chemistry, 2009, 52 (15), 4810-4819) (6 g, 27.7 mmol) was dissolved in N-methyl-2-pyrrolidinone (NMP) (60 mL) and to this was added DIPEA (7.27 mL, 41.6 mmol) and 5,7-dichloropyrido[3,4-b]pyrazine (5.55 g, 27.7 mmol). This was split between 4 large microwave vials and each was heated at 130 C. for 30 min. They were monitored by LCMS and were given a further 10 min at 130 C. The reaction mixtures were partitioned between ethyl acetate (700 ml) and diluted aqueous ammonium chloride (1 litre). The aqueous was reextracted with ethyl acetate (300 ml) and the combined organics were washed with aqueous ammonium chloride (500 ml), dried over sodium sulfate and concentrated in vacuo to yield a crude brown oil. It was dissolved in DCM and passed through silica (70 g) eluting with DCM (6*40 ml) then 5% ethyl acetate in DCM (2*40 ml), 10% ethyl acetate in DCM (5*40 ml) then 15% ethyl acetate in DCM (2*40 ml) then 20% ethyl acetate in DCM (2*40 ml). Appropriate fractions were combined and concentrated in vacuo to yield: N8231-100-2, orange-yellow slightly gummy solid, 7.7 g LCMS (Method B): Rt=1.17 min, MH+ 380

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 5,7-Dichloropyrido[3,4-b]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLAXO GROUP LIMITED; Atkinson, Francis Louis; Atkinson, Stephen John; Barker, Michael David; Douault, Clement; Garton, Neil Stuart; Liddle, John; Patel, Vipulkumar Kantibhai; Preston, Alexander G.; Shipley, Tracy Jane; Wilson, David Matthew; Watson, Robert J.; US2014/5188; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 89180-45-0,Some common heterocyclic compound, 89180-45-0, name is 5-Chloro-2-hydroxypyrazine, molecular formula is C4H3ClN2O, 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.

To a 50 mL round bottom flask equipped with a stir bar was added 5- chloropyrazin-2-ol (250 mg, 1.9 15 mmol), 2-(4-fluorophenyl)ethanol (268 mg, 1.9 15 mmol), triphenylphosphine (603 mg, 2.298 mmol) and THF (10 mL). To the stirred solution was added DIAD (0.447 mL, 2.298 mmol). The solution had a mild exotherm, then cooled within 5 minutes. The solution was stirred at RT for 2 hrs. The reactionsolution was concentrated in vacuo and the resulting oil was purified via silica gel chromatography (40 g column, 5-40% EtOAc:Hex) to afford the product 2-chloro-5-(4-fluorophenethoxy)pyrazine (330 mg, 1.306 mmol, 68.2 % yield) as a white solid. ?H NMR (500 MHz, CDC13) 8.10 (d,J=1.3 Hz, 1H), 8.01 (d,J=1.3 Hz, 1H), 7.25 (dd, J=8.6, 5.4 Hz, 2H), 7.03 (t, J=8.7 Hz, 2H), 4.52 (t, J=6.9 Hz, 2H), 3.09 (t, J=6.9 Hz, 2H). LCMS (M+1) = 253.0.

The synthetic route of 89180-45-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VIIV HEALTHCARE UK (NO.5) LIMITED; BELEMA, Makonen; BOWSHER, Michael S.; DESKUS, Jeffrey A; EASTMAN, Kyle J.; GILLIS, Eric P; FRENNESSON, David B; IWUAGWU, Christiana; KADOW, John F.; NAIDU, B. Narasimhulu; PARCELLA, Kyle E.; PEESE, Kevin M; SAULNIER, Mark G; SIVAPRAKASAM, Prasanna; (463 pag.)WO2018/127800; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 19745-07-4,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.

Preparation of 4-benzyl- 1 -(5-chloropyrazin-2-yl)piperidin-4-amine. To a solution of 2,5-dichloropyrazine (0.1316 mL, 0.7243 mmol) in DMSO (10 mL) were added K2CO3 (300.3 mg, 2.173 mmol) followed by 4-benzylpiperidin-4-amine bis(2,2,2- trifluoroacetate) (303 mg, 0.72 mmol). The reaction was sealed and heated at 75 °C overnight. After cooling to RT, the reaction was diluted with EtOAc (10 mL) and water (20 mL). After phase-separation, the aqueous was extracted with EtOAc (2x). The combined organic extracts were concentrated and used directly in the next step. MS (apci) m/z = 303.1 (M+H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2,5-Dichloropyrazine, its application will become more common.

Reference:
Patent; ANDREWS, Steven W.; ARONOW, Sean; BLAKE, James F.; BRANDHUBER, Barbara J.; COLLIER, James; COOK, Adam; HAAS, Julia; JIANG, Yutong; KOLAKOWSKI, Gabrielle R.; MCFADDIN, Elizabeth A.; MCKENNEY, Megan L.; MCNULTY, Oren T.; METCALF, Andrew T.; MORENO, David A.; RAMANN, Ginelle A.; TANG, Tony P.; REN, Li; WALLS, Shane M.; (946 pag.)WO2018/71454; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem