Tag: M.W=100-200

Electric Literature of 59489-71-3, A common heterocyclic compound, 59489-71-3, name is 2-Amino-5-bromopyrazine, molecular formula is C4H4BrN3, 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.

Description 65: 2-bromo-5-iodopyrazine (D65); In a 1000 ml, ice bath cooled round-bottomed flask was dissolved 5-bromo-2-pyrazinamine D64 (11.3 g) in Acetonitrile (125 ml)/water (188 ml). In the mixture HI 67% water solution (45 ml, 401 mmol) was added. To the solution was added dropwise during 150 minutes a solution of sodium nitrite (31.4 g, 455 mmol) in water (125 ml). After the addition the reaction mixture was sealed, was let to warm-up to room temperature and was heated at 50 0C for 30 hours. After cooling the mixture was poured into 800 ml of 20% NaOH and was extracted with Et2O (3 x 800 ml). Gathered Et2O layers were washed with Na2S2Os saturated solution, dried over Na2SO4 and the solvent was evaporated. The crude was purified by Silica Chromatography (Biotage SP – column size 34Og) using DCM 100% to DCM/MeOH 90: 10 as eluent. It was recovered the title compound D65 (896 mg) as yellow powder. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 8.49 – 8.56 (m, 1 H) 8.65 (d, 1 H)

The synthetic route of 59489-71-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; AMANTINI, David; DI FABIO, Romano; WO2010/122151; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 27398-39-6,Some common heterocyclic compound, 27398-39-6, name is 3-Chloropyrazine-2-carboxylic acid, molecular formula is C5H3ClN2O2, 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 solution of 3-ehioropyrazine-2-earboxyiic acid (100 rng, 0,63 mmoi) in DCM/MeOH (2 mL: 0.2 mL) was added TMSCHN2 (0.47 rnL, 0.95 mrnoi) at RI and theresulting mixture stirred at RT for 2 h. Acetic acid (0.2 mL) was added and the mixture diluted with water (2 mL) and extracted with DCM (4 mL x 3). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give the title compound as a oil. LRMS m/z (M+H) 173.0 found, 173.0 required.

The synthetic route of 27398-39-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; KUDUK, Scott D.; LIVERTON, Nigel; LUO, Yunfu; SKUDLAREK, Jason; (79 pag.)WO2016/95204; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 14508-49-7, name is 2-Chloropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Application In Synthesis of 2-Chloropyrazine

Using Procedure AU-3 (Table 5) with 2-chloropyrazine the title compound 476 was obtained (4.4 g, 46%) as a yellow solid. MS (m/z): 111.0 (M+H)

The synthetic route of 14508-49-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Forum Pharmaceuticals, Inc.; Rogers, Kathryn; Patzke, Holger; (315 pag.)US2017/749; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 4430-75-5,Some common heterocyclic compound, 4430-75-5, name is Octahydro-2H-pyrido[1,2-a]pyrazine, molecular formula is C8H16N2, 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.

1-fluoro-2-nitrobenzene (1.2 g, 8.56 mmol), Octahydro-1H-pyrido [1, 2-a] pyrazine (1.0 g, 7.13mmol), N,N-Diisopropylethylamine (1.9 mL, 10.7 mmol) were added to N,N-dimethylformamide (20 mL), and the reaction was heated to 90 C for 4 hours under nitrogen. After the reaction was cooled to room temperature, the reaction solution was diluted with water (80 mL), extracted with dichloromethane (30 mL X 3), the organic phases were combined and washed successively with water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, the obtained crude product was passed through a silica gel chromatography column (petroleum ether: ethyl acetate (V:V) = 5:1) and further purified to give the title compound (yellow oil, 1.74 g, 93.4%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Octahydro-2H-pyrido[1,2-a]pyrazine, its application will become more common.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Jin Chuanfei; Yi Chao; Zhang Yingjun; Duan Zhenfang; Wang Kezhu; (25 pag.)CN108409728; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 89123-58-0,Some common heterocyclic compound, 89123-58-0, name is 5-Bromopyrazine-2,3-diamine, molecular formula is C4H5BrN4, 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.

The title compound of PREPARATION 45 (240 mg, 1.2 mmol) and 1,1?- carbonyldiimidazole (240 mg, 1.5 mmol) were dissolved in 3 ml butyronitrile and the mixture was stirred in a sealed microwave tube for 15 mm at room temperature affording a thick white suspension. The title compound of PREPARATION 73 (220 mg,1.2 mmol) was added and the reaction was heated 18000 under microwave irradiationfor 2 h. The mixture was allowed to cool and was evaporated under reduced pressure. The residue was purified by flash chromatography (methanol-dichloromethane gradient, 0:100 rising to 10:90) to give 240 mg (0.66 mmol, 58% yield) of the title compound as a white solid. Purity 97%.1H NMR (400 MHz, DMSO-d6) oe ppm 8.54 (s, 1H), 8.44 (s, 1H), 8.27 (s, 1H), 5.40 (s,2H), 2.50 (s, 3H).UPLC/MS (3 mm) retention time 0.98 mm.LRMS: mlz 361, 363 (M+1, 1 xBr)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromopyrazine-2,3-diamine, its application will become more common.

Reference:
Patent; ALMIRALL, S.A.; AIGUADE BOSCH, Jose; CONNOLLY, Stephen; EASTWOOD, Paul Robert; ROBERTS, Richard Spurring; SEVILLA GOMEZ, Sara; CATURLA JAVALOYES, Juan Francisco; (110 pag.)WO2017/64068; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 1111638-10-8, 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. 1111638-10-8, name is 3-Chloro-5H-pyrrolo[2,3-b]pyrazine, This compound has unique chemical properties. The synthetic route is as follows.

Step 1. 2-(3-chloro-5H-pyrroloI23″b]pyrazin-5-yl)-N-(2,2,2-trifluoroethyl)acetamideTo a solution of 3~chloro-5H-pyrrolo[2,3-b]pyrazine (50 mg, 0.326 mmol) in DMF (2 mL) at room temperature was slowly added sodium hydride (20.3 mg, 0.508 mmol). The reaction mixture was allowed to stir for 15 minutes. 2-Bromo-N-(2,252-trifluoroethyl)acetamide (88 mg, 0.40 mmol) was then added and the reaction mixture allowed to stir for 1 hour. Ethanol (0.1 mL) was added to the reaction mixture which was then loaded on to a silica cartridge and purified using medium pressure liquid chromatography (0-10%, methanol/dichloromethane) to yield the title compound. LC-MS (ES, m/z): 293.0 [M+H]+. iH-NMR (400Hz, CDCI3 ppm): 8.95 (1H, t, J=6.1Hz), 8.47 (1H, s), 7.91 (1H, d, J=3.6Hz), 6.72 (1H, d, J=3.6Hz), 5.01 (2H, s), 3.93 (2H, m).

The chemical industry reduces the impact on the environment during synthesis 3-Chloro-5H-pyrrolo[2,3-b]pyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; MERCK SHARP & DOHME CORP.; CASH, Brandon; FISCHER, Christian; GARCIA, Yudith; JUNG, Joon; KATZ, Jason; KIM, June; RIVKIN, Alexey; SCHELL, Adam; SIU, Tony; WITTER, David; ZHOU, Hua; WO2011/137022; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 768-05-8, A common heterocyclic compound, 768-05-8, name is Pyrazinoic acid hydrazide, molecular formula is C5H6N4O, 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.

Pyrazine-2-carbonyl azide. Pyrazine-2-carboxylic acid hydrazide (11.1 g, 80 mmol) was dissolved in 140 mL of water and charged with 6N HC1 (13.3 mL, 80 mmol) and cooled to 0 C. To the stirred reaction mixture was added a solution of sodium nitrite (8. 3 g, 120 mmol) in 80 mL of water was added slowly over a period of 15-30 minutes using an addition funnel. After the addition was complete the reaction was warmed to room temperature and stirred for an additional 5h. The solution was the neutralized by the careful addition of solid NAHCO3 and then extracted with CHC13 (3x). The pooled organic fractions were dried over NA2S04, filtered, concentrated and dried under high vacuum overnight to yield 2.5 g (21%) the title acyl azide. The product was used in subsequent steps without PURIFICATION.

The synthetic route of 768-05-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/16909; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 939412-86-9, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 939412-86-9 name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

A 30 vial was charged with 8- (methoxycarbonyl) bicyclo [3.2.1] octane-3-carboxylic acid (830 mg, 3.91 mmol) , HATU (1784 mg, 4.69 mmol) , TEA (1.635 mL, 11.73 mmol) and DCM (20 mL) . The mixture was stirred at 30 for 30 minutes. Then (3-chloropyrazin-2-yl) methanamine hydrochloride (845 mg, 4.69 mmol) was added, the resulting mixture was stirred at 30 for 16 hours. The reaction mixture was diluted with EtOAc (50mL) and washed with brine (50mLx3) . The organic layer was evaporated to dryness and the residue was purified via combi flash (EtOAc in petroleum from 0to 50) to give the title compound. 1H NMR (400 MHz, CDCl3) : delta 8.46 (d, J 2.0 Hz, 1H) , 8.32 (brs, 1H) , 6.85 (brs, 1H) , 4.69-4.59 (m, 2H) , 3.72 (s, 3H) , 2.70-2.50 (m, 4H) , 2.05-1.93 (m, 2H) , 1.89-1.77 (m, 2H) , 1.70 (m, 2H) , 1.65-1.56 (m, 2H) ppm.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, (3-Chloropyrazin-2-yl)methanamine hydrochloride, and friends who are interested can also refer to it.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIU, Jian; KOZLOWSKI, Joseph A.; ANDRESEN, Brain M.; BOGA, Sobhana Babu; GAO, Xiaolei; GUIADEEN, Deodialsingh; CAI, Jiaqiang; LIU, Shilan; WANG, Dahai; WU, Hao; YANG, Chundao; (111 pag.)WO2016/106624; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 23611-75-8, 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 23611-75-8 as follows.

Step 3: Preparation of (6-chloropyrazin-2-yl)methanol To a solution of methyl 6-chloropyrazine-2-carboxylate (2.0 g, 11.6 mmol) in water (20 mL) at 0 C. was added NaBH4 (2.3 g, 58.0 mmol) portionwise. The reaction mixture was warmed to r.t. and stirred for 30 min, followed by addition of satd. aq. K2CO3 (40 mL) and EtOH (20 mL). The resulting mixture was stirred for another 1 hr and extracted with EA (2*20 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated and purified by standard methods to afford (6-chloropyrazin-2-yl)methanol. LC-MS: m/z 145.0 (M+H)+.

According to the analysis of related databases, 23611-75-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AGIOS PHARMACEUTICALS, INC; Konteatis, Zenon D.; Popovici-Muller, Janeta; Travins, Jeremy; Zahler, Robert; Cai, Zhenwei; Zhou, Ding; US2015/18328; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 55557-52-3,Some common heterocyclic compound, 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, molecular formula is C5H2ClN3, 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.

General procedure: In a degassed solution of DME/H2O (2:1) (12mL/mmol of diazine), were successively introduced S-Phos (10mol%) and Pd(OAc)2 (5mol%). The solution was heated at 80C for 10min then sodium carbonate (4.0equiv), appropriate boronic acid (1.05 or 1.5equiv) and appropriate diazine (1.0equiv) were added. The solution was then refluxed (15min or overnight) under Ar. The resulting mixture was filtered on Celite and washed with ethyl acetate and water. The aqueous phase was then extracted three times with ethyl acetate. The combined organic phase was dried over MgSO4 and evaporated to dryness. The residue was purified by column chromatography (eluent: PE/EtOAc) to give the desired product.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Chloropyrazine-2-carbonitrile, its application will become more common.

Reference:
Article; Fresneau, Nathalie; Cailly, Thomas; Fabis, Frederic; Bouillon, Jean-Philippe; Tetrahedron; vol. 69; 26; (2013); p. 5393 – 5400;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem