Month: May 2021

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. 123-32-0, name is 2,5-Dimethylpyrazine, This compound has unique chemical properties. The synthetic route is as follows., Safety of 2,5-Dimethylpyrazine

To a solution of 2,5-dimethylpyrazine (500 mg, 4.62 mmol) in carbon tetrachloride (7 mL) was added NCS (679 mg, 5.09 mmol) followed by BPO (20 mg) and the mixture was heated to 80 C. for 6 hours. The mixture was diluted with DCM and extracted with saturated aqueous sodium sulfite solution and brine. The organic layer was dried and concentrated to give a crude product which was purified via silica gel chromatography eluting with petroleum ether/ethyl acetate (1:0 to 15:1) to give 2-(chloromethyl)-5-methylpyrazine (133 mg, 20.19% yield) as yellow oil. LCMS retention time 0.557 min; LCMS MH+ 143.

According to the analysis of related databases, 123-32-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; HYDRA BIOSCIENCES, INC.; Chenard, Bertrand L.; Gallaschun, Randall J.; Kimball, Spencer David; US2014/275528; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 4858-85-9, A common heterocyclic compound, 4858-85-9, name is 2,3-Dichloropyrazine, molecular formula is C4H2Cl2N2, 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.

In a 100 mL three-necked flask, under N2 protection,Add magnesium chips (0.729g, 30mmol),Add 1 iodine (initiator),Add 10 mL of dry THF to immerse the magnesium chips,Start stirring,Add 2,3-dichloropyrazine (0.148 g, 1 mmol),Heating causes the reaction,THF reflux,The color of the iodine particles fades,Magnesium turnings indicate brightening,Lead to success.Stop heating,A solution of 2,3-dichloropyrazine in THF (4.291 g, 29 mmol, dissolved in 20 mL of dry THF) was slowly added dropwise.After the drop is over,Heated back to 65 degrees CelsiusFlow 1h.Get a new format reagent,The concentration is about 1 mol/L.At 100mLIn an eggplant-shaped bottle,JoinTetrabutylammonium chloride (0.278 g, 1 mmol),Under N2 protection,Slowly add the previously prepared format reagent (15mL, 15mmol).Stir at room temperature for 10 min,Then add diethylene glycol dimethyl ether (2.012g,15mmol),After stirring for 30 min at room temperature,Cool down to 0 to 5 degrees Celsius,A solution of 4-methylimino-N-2-pyridine-benzamide in THF (2.251 g, 10 mmol, 1.0 M in THF) was slowly added.After the addition was completed, the reaction solution was gradually warmed to room temperature for 2 h.After completion of the reaction, the reaction was quenched with 5 mL of aqueous hydrogen chloride (10%).Add 150 mL of a saturated aqueous solution of sodium bicarbonate,Extract twice with 100 mL of ethyl acetate.The organic layers were combined and washed with a saturated aqueous solution of sodium chloride.Dry over anhydrous sodium sulfate for 1 h,Dry under reduced pressure to obtain a crude product.Column chromatography with ethyl acetate/petroleum ether (1:2) gave 4-[amino-(3-chloro-2-pyridin2.82 g of pyrazinylmethyl]-N-(2-pyridyl)benzamide,The yield was 85% and the purity was 98%.

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; Anqing Qichuang Pharmaceutical Co., Ltd.; Wu Xueping; Chu Yijie; Chen Yao; Wang Min; (10 pag.)CN109020977; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route 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 suspension of sodium hydride (278 mg, 6.95 mmol, 60percent in oil) in DMF (10 mL) was added 1H-pyrazole (279 mg, 4.11 mmol) at RT and the resulting mixture stirred at RT for 0.5 h. 3-Chloropyrazine-2-carboxylic acid (500 mg, 3.16 mmol) was added and the mixture heated to 60°C for 2 h. After cooling to RT, water (20 mL) was added and the mixture extracted with 4.7percent MeOH in DCM (20 mL x 3). The combined organic layers were washed with brine, dried over Na2S04, filtered and concentrated in vacuo to give the title compound as a solid. LRMS m/z (M+H) 191.0 found, 191.0 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.; LIVERTON, Nigel; KUDUK, Scott D.; BESHORE, Douglas; LUO, Yunfu; MENG, Na; YU, Tingting; (114 pag.)WO2016/65585; (2016); 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

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

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

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. 1422772-78-8, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid, A new synthetic method of this compound is introduced below., Recommanded Product: 2-Bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

To a solution of 2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1.4 g,5.22 mmol) in ethanol (20 mL) was added sulfuric acid (0.5 mL) at 0 C. and the mixture was stirred at 80 C. for 1 hour. After cooling the reaction mixture was quenched with ice and extracted with ethyl acetate. The organic layer was washed with water,brine,dried over anhydrous sodium sulfate,filtered and concentrated in vacuo. The crude material was purified using flash chromatography (10% ethyl acetate/hexane) to provide ethyl 2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate as a brown liquid (1.4 g,80% yield): MS (ES) m/z 272 (M+H).

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; ACLARIS THERAPEUTICS, INC.; JACOBSEN, Eric Jon; ANDERSON, David Randolph; BLINN, James Robert; HOCKERMAN, Susan Landis; HEIER, Richard; MUKHERJEE, Paramita; (196 pag.)US2020/48262; (2020); 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

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

Adding a certain compound to certain chemical reactions, such as: 91775-62-1, name is 3-Bromo-8-methoxyimidazo[1,2-a]pyrazine, belongs to pyrazines compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 91775-62-1, Product Details of 91775-62-1

To a well stined solution of silver(I)fluoride (3.4g, 26.5 mmol) in DMF (20 ml), wasadded trifluoromethyltrimethylsilane and stined at room temperature for 0.5h. To the reactionmixture, was added copper (2.4g, 39.0 mmol) and stined at room temperature for 4h. Then added 3-bromo-8-methoxyimidazo[1,2-a]pyrazine (5.5g, 24.1 mmol) and stined at 90C for 5h. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was washed with water, brine, dried over anhydrous sodium sulfate and concentrated underreduced pressure to get the crude product. The crude product was purified by column chromatography (60-120 mesh silica gel and 10- 20% EtOAc in hexane) to obtain 8-methoxy-3- (trifluoromethyl)imidazo[ 1 ,2-a]pyrazine (1 .5g, 29%). LC-MS: 218.3 [M+Hf.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Bromo-8-methoxyimidazo[1,2-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; AURIGENE DISCOVERY TECHNOLOGIES LIMITED; KOTRABASAIAH UJJINAMATADA, Ravi; PANDIT, Chetan; (152 pag.)WO2016/185342; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem