Tag: M.W=100-200

Reference of 36070-80-1, 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. 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

In a 2L stainless steel autoclave,Add 317 g (2.0 mol) of 5-chloropyrazine-2-carboxylic acid, cooling to 0 ~ 10 C, adding anhydrous hydrogen fluoride 480g (24mol),The temperature was further lowered to -40 C, and sulfur tetrafluoride 476 (4.4 mol) was introduced.Then, the temperature was slowly raised to 75 to 80 C, and the reaction was kept for 6 hours.At the end of the reaction, the reaction hydraulic pressure is poured into the ice water.Neutralize to pH=7 with 10% aqueous sodium carbonate solution.The organic layer is separated and steamed,The obtained product was subjected to rectification to obtain 329 g of 2-chloro-5-trifluoromethylpyrazine in an amount of 99%.The yield was 90%.

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-Chloropyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Jinkai (Liaoning) Chemical Co., Ltd.; Li Degang; Wang Yongcan; Fu Limin; Tang Xiaofeng; Qi Yue; Sun Jie; Yang Yang; Zhang Wei; (6 pag.)CN107840828; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 274-79-3, A common heterocyclic compound, 274-79-3, name is Imidazo[1,2-a]pyrazine, molecular formula is C6H5N3, 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.

General procedure: Imidazo[1,2-a]pyrazines (0.3 mmol), 2-chlorobenzaldehyde (0.33 mmol, 1.1 equiv.), K2CO3 (0.9 mmol, 3 equiv.), PivOH (30 mol%), Pd(OAc)2 (7.5 mol %), and Xantphos (15 mol %) were added to a 10 mL round-bottomed flask, and then a mixed solvent of 3 mL of DMF and 30 uL of H2O was added. The mixture was stirred under air at 110 C for 24 h. After the reaction was complete, the mixture was washed with water and extracted with ethyl acetate three times. The combined organic layer was dried with anhydrous MgSO4 and filtered. The filtrate was concentrated in vacuo. The crude product was purified by flash chromatography on silica gel using dichloromethane/methanol as the eluent to give the pure product.

The synthetic route of 274-79-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Mu, Bing; Li, Jingya; Zou, Dapeng; Wu, Yusheng; Chang, Junbiao; Wu, Yangjie; Tetrahedron Letters; vol. 58; 52; (2017); p. 4816 – 4821;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 20737-42-2, name is 3-Oxo-3,4-dihydropyrazine-2-carboxylic acid, 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. name: 3-Oxo-3,4-dihydropyrazine-2-carboxylic acid

Preparation of methyl (S)-3-(4-cyanophenyl)-2-((4-((3-((4-(3-hydroxypyrazine-2- carbonyl)piperazin-1-yl)methyl)phenyl)amino)-1,3,5-triazin-2-yl)amino)propanoate (TA1026). HATU (1.2 equiv., 45 mg, 0.12 mmol) was added to a solution of 3- hydroxypyrazine-2-carboxylic acid (I-6, 1.1equiv., 15 mg, 0.11 mmol) in anhydrous DCM (1.5 mL) and DIPEA (3equiv., 0.040 mL, 0.23 mmol). After being stirred at r.t.10 minutes, TA1047 (1equiv., 46 mg, 0.098 mmol) was added. The resulting suspension was stirred at r.t. 1 h, followed by DMF (0.1 mL). Then the reaction was stirred for another 2 h until the LCMS analysis showed complete consumption of the starting material. The crude residue was then purified by reverse phase preparative HPLC (XBridge BEH, 19×150 mm, 5mum, C18 column; ACN/water with 0.1% formic acid modifier, 20mL/min), affording Compound TA1026 (15.1 mg, 25%) as a yellow solid.1H NMR (400 MHz, Methanol-d4) d 8.12 (d, J = 10.2 Hz, 1H), 7.71 – 7.65 (m, 2H), 7.61 (d, J = 8.0 Hz, 2H), 7.49 (s, 2H), 7.43 (d, J = 7.9 Hz, 3H), 7.34- 7.27 (m, 1H), 7.08 (dd, J = 17.7, 7.0 Hz, 1H), 4.96 (dd, J = 8.6, 5.8 Hz, 1H), 3.83- 3.77 (m, 2H), 3.71 (s, 2H), 3.60 (s, 2H), 3.43- 3.39 (m, 3H), 3.25- 3.14 (m, 3H), 2.58 (dt, J = 36.9, 4.7 Hz, 5H). MS (m/z): 595 [M+1]+, LCMS purity: 99%.

The synthetic route of 3-Oxo-3,4-dihydropyrazine-2-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ADURO BIOTECH, INC.; KATIBAH, George Edwin; KIM, Jung Yun; NDUBAKU, Chudi Obioma; ROBERTS, Tucker Curran; TJANDRA, Meiliana; (165 pag.)WO2019/245910; (2019); 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. 4774-14-5, name is 2,6-Dichloropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 2,6-Dichloropyrazine

To a solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (LXIII) (2 g,9.58 mmol) in dry DMF (19.2 mL) was added DIPEA (8.37 ml, 47.9 mmol). To this mixture wasadded 2,6-dichloropyrazine (LXIV) (1.428 g, 9.58 mmol) and the reaction was stirred at 95C for3 h. The reaction was quenched with water (20 mL) and extracted with EtOAc. The organic layerwas dried over anhydrous Na2504, filtered and concentrated. The residue was purified by silica gel column chromatography (40 g) (100% hexanes-*hexanes:EtOAc 1:1) to yield tert-butyl (1-(6- chloropyrazin-2-yl)azetidin-3-yl)carbamate (LXV) (2.2882 g, 8.04 mmol, 84 % yield) as a white solid. ESIMS found for C,2H,7C1N402 mlz 285.1 (M+H).

The synthetic route of 4774-14-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SAMUMED, LLC.; KC, Sunil Kumar; WALLACE, David Mark; CAO, Jianguo; CHIRUTA, Chandramouli; HOOD, John; (240 pag.)WO2017/23975; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 136927-64-5, These common heterocyclic compound, 136927-64-5, name is 1-Chloropyrrolo[1,2-a]pyrazine, 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.

To a solution of the product of Example 4A in dioxane (1mL) were added 1- chloropyrrolo[1,2-a]pyrazine (64.3 mg, 0.421 mmol), palladium(II) acetate (7.89 mg, 0.035 mmol), xantphos (20.3 mg, 0.035 mmol), and potassium carbonate (146 mg, 1.05 mmol). The reaction mixture was heated at 80 C for 18 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified with flash column chromatography (SiO2, heptane:ethyl acetate 0~100%) followed by preparative HPLC [Waters XBridge C185 mum OBD column, 30 × 100 mm, flow rate 40 mL/minute, 5-100% gradient of acetonitrile in buffer (0.1 % trifluoroacetic acid)] to give the title compound (8 mg, 0.020 mmol, 6% yield). 1H NMR (400 MHz, DMSO-d6) delta ppm 8.92 (s, 1H), 7.88 (d, J = 5.7 Hz, 1H), 7.86 – 7.82 (m, 1H), 7.52 (d, J = 4.3 Hz, 1H), 7.47 (t, J = 8.8 Hz, 1H), 7.05 (dd, J = 11.3, 2.9 Hz, 1H), 7.00 (d, J = 5.7 Hz, 1H), 6.87 – 6.81 (m, 2H), 4.51 (s, 2H), 2.57 (s, 6H); MS (ESI+) m/z 401 (M+H)+.

The synthetic route of 136927-64-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CALICO LIFE SCIENCES; ABBVIE, INC.; SIDRAUSKI, Carmela; PLIUSCHEV, Marina; FROST, Jennifer, M.; BLACK, Lawrence, A.; XU, Xiangdong; SWEIS, Ramzi, Farah; SHI, Lei; ZHANG, Qinwei, I.; TONG, Yunsong; HUTCHINS, Charles, W.; CHUNG, Seungwon; DART, Michael, J.; (661 pag.)WO2017/193063; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 95-89-6, name is 3-Chloro-2,5-dimethylpyrazine, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 3-Chloro-2,5-dimethylpyrazine

Intermediate 18: 3,6-d imethyllyrazin-2-amineAmmonia in water (3 mL, 48.5 mmol) was added to 3-chloro-2,5-dimethylpyrazine (0.121 mL, 1 mmol) and the mixture heated by microwaves to 165 C for 7 hours. Following LCMS analysis, the reaction was then reheated to 165 C for a further 16 hours, by microwaves. After cooling, thesolvent was removed under a stream of nitrogen and the crude redissolved in dichloromethane (20mL). Water (25 mL) was added and the mixture basified to pHl4 using sodium hydroxide solution(18 N). The organic layer was removed and the aqueous layer extracted with dichloromethane (5 x25 mL). The organic phases were combined and dried using a hydrophobic frit, then evaporated invacuoto give the title product (109 mg). This was used directly in the next step with no furtherpurification. LCMS (2 mm, high pH) Rt 0.47 mi m/z (ESj 124 (M+H).1H NMR (400 MHz, CHLOROFORM-o) O ppm 7.73 (5, 1 H), 4.42 (br. s., 2 H), 2.37 (5, 3 H), 2.35 (5, 3H).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 95-89-6.

Reference:
Patent; GLAXO GROUP LIMITED; BIRAULT, Veronique; CAMPBELL, Amanda, Jennifer; HARRISON, Stephen; LE, Joelle; SHUKLA, Lena; WO2013/160419; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 33332-28-4, 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. 33332-28-4, name is 2-Amino-6-chloropyrazine, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 2-amino-6-chloropyrazine (5 g, 38.60 mmol) in a mixture of anhydrous chloroform (120 mL), anhydrous acetonitrile (12 mL) and anhydrous methanol (12 mL) was addedslowly, at 0CC, NBS (7.56 g, 42.45 mmol, 1.1 eq.) and the mixture was warmed to room temper-ature and continuously stirred for 1 h. The excess solvent was removed in vacuo and the obtained crude material (light brown solid) was purified by column chromatography (Hexane/DCM/MeOH = 50/50/0 then 0/1 00/0 then 0/95/5) to afford 5-bromo-6-chloropyrazin-2-amine(6.34 g, 30.42 mmol, 79percent) as white crystals. ESI-MS: 209.90 [M+H]+. 1 H NMR (300 MHz,CDCI3) 6 7.69 (s, 1 H), 4.78 (br s, 2H).

The chemical industry reduces the impact on the environment during synthesis 2-Amino-6-chloropyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; SELVITA S.A.; BOBOWSKA (NEE WITKOWSKA), Aneta; GALEZOWSKI, Michal; NOWAK, Mateusz; COMMANDEUR, Claude; SZEREMETA-SPISAK, Joanna; NOWOGRODZKI, Marcin; OBARA, Alicja; DZIELAK, Anna; LOZINSKA, Iwona; DUDEK (NEE SEDLAK), Marcelina; JANIGA, Anita; REUS, Jacek; WRONOWSKI, Marek; ZASTAWNA, Magdalena; RADZIMIERSKI, Adam; SWIRSKI, Mateusz; ZACHMANN, Julian; FABRITIUS, Charles-Henry; PORTER, Rod; FOGT, Joanna; (276 pag.)WO2019/2606; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 16298-03-6, 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 16298-03-6 as follows.

To a solution of methyl 3-amino- pyrazine-2- carboxylate (5.00 g, 32.7 mmol) in 1,2-dimethoxyethane (80 mL) were added ?2 (4.14 g, 16.3 mmol), copper(I) iodide (1.87 g, 9.80 mmol) and cesium iodide (8.48 g, 32.7 mmol) undernitrogen. Then isoamyl nitrite (13.2 mL, 98.0 mmol) was added dropwise at 20 °C. The reaction was stirred at 75 °C for 2 h, then quenched with water (100 mL). The aqueous layer was extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (30 mL), dried over anhydrous MgSO4 and filtered. The filtrate was concentrated in vacuo to give a residue, which was purified by silica gel chromagraphy eluting withPE/EtOAc (5i02, PE: EtOAc = 1: O1O:1, v/v) to give the title compound. MS (ESI) mlz:264.7 [M+Hj ?H NMR (400MHz, DMSO-d6) oe = 8.71 (d, J=2.2 Hz, 1H), 8.63 (d, J2.0Hz, 1H), 3.93 (s, 3H)

According to the analysis of related databases, 16298-03-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MILLER, Michael; CHOBANIAN, Harry, R.; HE, Shuwen; HAO, Jinsong; PIO, Barbara; GUO, Yan; XIAO, Dong; (213 pag.)WO2018/118670; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 5521-58-4,Some common heterocyclic compound, 5521-58-4, name is 5-Methylpyrazin-2-amine, molecular formula is C5H7N3, 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.

Example 9: (/?)-l-[(5-Methyl-pyrazin-2-yIcarbamoyl)-methyl]-3-(l-thiophen-2-yl5 cycloheptanecarbonyloxy)-l-azonia-bicyclo[2.2.2]octane bromide To a mixture of 5-methyl-pyrazin-2-ylamine and cesium carbonate (11.2 g) dissolved dry DMF (30 mL) was added by dropwise addition bromoacetylbromide (2.89 g) and mixture stirred at rt for 2 hours. Water (200 mL) was added and the mixture extracted ethyl acetate (2 x 100 mL) and dried over magnesium sulfate. Concentration of the exi to -50 mL and addition of ts°hexane (100 mL) gave the sub-titled compound as a sol (1-64 g).1H NMR (400 MHz, DMSO-D6) delta 1 1.06 (IH, s), 9.17 (IH, s), 8.31 (IH, d), 4.16 (2H, 2.46 (3H, s).

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

Reference:
Patent; ASTRAZENECA AB; ARGENTA DISCOVERY LIMITED; WO2009/138707; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 72788-94-4, 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. 72788-94-4, name is 2-Chloro-5-(hydroxymethyl)pyrazine, This compound has unique chemical properties. The synthetic route is as follows.

Et3N (4.17 mL, 29.9 mmol) and mesyl chloride (1.57 mL, 20.3 mmol) were added to a solution of (5-chloro-2-pyrazinyl)methanol (45) (obtained by chlorination and reduction of 5-hydroxypyrazine-2-carboxylic acid, as reported by Kiener et al., 1994) (1.443 g, 9.98 mmol) in anhydrous THF (20 mL) at 0 0C. The mixture was stirred at 0 0C for 0.5 h, then partitioned between EtOAc and water. The organic fraction was dried (MgSO4) and the solvent was removed under reduced pressure to give the crude mesylate. The mesylate was dissolved in acetone (40 mL), sodium iodide (7.5 g, 50 mmol) was added, and the mixture was refluxed for 1 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc and water. The organic fraction was concentrated under reduced pressure and the residue was chromatographed on silica gel (eluting with CH2Cl2) to give 2-chloro-5- (iodomethyl)pyrazine (46) (1.54 g, 61%), which was used immediately due to its instability.

The chemical industry reduces the impact on the environment during synthesis 2-Chloro-5-(hydroxymethyl)pyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; GLOBAL ALLIANCE FOR TB DRUG DEVELOPMENT; DENNY, William, Alexander; THOMPSON, Andrew, M.; BLASER, Adrian; MA, Zhenkun; PALMER, Brian, Desmond; SUTHERLAND, Hamish, Scott; KMENTOVA, Iveta; WO2011/14774; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem