Author: Jessica.F

Synthetic Route of 22047-25-2, A common heterocyclic compound, 22047-25-2, name is Acetylpyrazine, molecular formula is C6H6N2O, 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.

3-Hydrazinylbenzoisothiazole-1,1-dioxide (138mg; 0.7mmol) and acetylpyrazine (122mg; 1mmol) were mixed in isopropanol (25mL), and acetic acid (1mL) was added. The reaction mixture was then stirred at 75C for 2days. The volatile compounds were then evaporated under reduced pressure, and the residue was suspended in diethyl ether/petroleum ether mixture (1:1, v/v; 30mL). Solid material was filtered, washed with additional diethyl ether/petroleum ether mixture (1:1, v/v; 60mL) and dried at 50C under vacuum. 3-(2-(1-(Pyrazin-2- yl)ethylidene)hydrazinyl)-1,2-benzothiazole 1,1-dioxide (4) was obtained with a yield of 164mg (78%) as a yellowish solid. 1H NMR (DMSO-d6): 2.55 and 2.61 (2x s, 3H); 7.92 (m, 2H); 8.10 (s, 1H); 8.45 and 8.70 (2x m, 1H); 8.75 (m, 2H); 9.30 (s, 1H); 11.70 and 12.37 (2x bs, 1H) ppm. 13C NMR (DMSO-d6): delta 12.8 (13.6); 121.7 (121.6); 124.2; 126.7; 129.6; 133.8 (134.1); 133.9; 142.5; 143.0; 143.6 (143.8); 145.3 (145.0); 149.8 (149.7); 154.7 (159.9) ppm. ESI-MS (m/z): 302 [M+H]+. Elem. Anal. Calcd. for C13H11N5O2S: C, 51.82; H, 3.68; N, 23.24. Found: C, 51.80; H, 3.72; N, 23.26.

The synthetic route of 22047-25-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Jakubek, Milan; Kejik, Zden?k; Kaplanek, Robert; Antonyova, Veronika; Hromadka, Robert; ?andrikova, Viera; Sykora, David; Martasek, Pavel; Kral, Vladimir; Bioorganic Chemistry; vol. 88; (2019);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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 33332-29-5 as follows. name: 2-Amino-5-chloropyrazine

Step 2: Synthesis of 2,5-dichloropyrazine To a stirred solution of 5-chloropyrazin-2-amine (1 g, 7.751 mmol) in conc. HCl (10 mL) was added aq. solution sodium nitrite (1.1 g, 15.89 mmol) at -10 C. over a period of 1 h, stirred for 1 h 0 C. and then at RT for 2 h. Progress of reaction was monitored by TLC. After reaction completion reaction mass neutralised with 50% NaOH solution and extracted with DCM. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 2% ethyl acetate in hexane as eluent to yield 2,5-dichloropyrazine (0.59 g, 15%) as colourless oil. MS: 184.1 [M-1]

According to the analysis of related databases, 33332-29-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Mankind Pharma Ltd.; Patil, Rakesh Ishwar; Verma, Jeevan; Shah, Dharmesh; Ali, Sazid; Bapuram, Srinivasa Reddy; Rai, Santosh Kumar; Kumar, Anil; (146 pag.)US2017/291910; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 939412-86-9, The chemical industry reduces the impact on the environment during synthesis 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, I believe this compound will play a more active role in future production and life.

A mixture of (trans)-2-((benzyloxy)carbonyl)-4-oxooctahydro-l H-pyrido [1 ,2-a] pyrazine-7-carboxylic acid (1.3 g, 3.9 mmol), (3-chloropyrazin-2-yl)methanamine hydrochloride (840 mg, 4.7 mmol), HATU (2.2 g, 5.8 mmol) and TEA (1.6 g, 15.6 mmol) in DMF (20 mL) was stirred at 25 C for overnight. Then the reaction mixture was poured into water and extracted with EA (50 ml*3). The combined organic phase was washed with brine (100 mL), dried over Na2S04, concentrated under vacuum to give the crude residue, which was purified by silica gel column chromatography (PE/THF = 1/3) to give (trans)-benzyl 7-(((3-chloropyrazin-2-yl)methyl)carbamoyl)-4- oxohexahydro-1 H-pyrido [l ,2-a]pyrazine-2(6H)-carboxylate (600 mg, yield 35.3 %). 1H NMR (400MHz, CD3OD) delta= 8.52 (d, J=2.5 Hz, 1H), 8.33 (d, J=2.3 Hz, 1H), 7.40 – 7.29 (m, 5H), 5.15 (br. s., 2H), 4.77 – 4.67 (m, 1H), 4.12 (br. s., 1H), 3.96 – 3.85 (m, 1H), 3.48 (br. s., 2H), 2.71 (t, J=12.5 Hz, 1H), 2.52 – 2.36 (m, 1H), 2.1 1 – 1.97 (m, 2H), 1.90 – 1.71 (m, 2H).

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, (3-Chloropyrazin-2-yl)methanamine hydrochloride, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK SHARP & DOHME CORP.; WU, Hao; KIM, Ronald M.; LIU, Jian; GAO, Xiaolei; BOGA, Sobhana Babu; GUIADEEN, Deodialsingh; LIU, Shilan; YANG, Chundao; WANG, Hongjian; WO2014/113932; (2014); A1;; ; Patent; MERCK SHARP & DOHME CORP.; WU, Hao; KIM, Ronald M.; LIU, Jian; GAO, Xiaolei; BOGA, Sobhana Babu; GUIADEEN, Deodialsingh; KOZLOWSKI, Joseph; YU, Wensheng; ANAND, Rajan; YU, Younong; SELYUTIN, Oleg B.; GAO, Ying-Duo; LIU, Shilan; YANG, Chundao; WANG, Hongjian; WO2014/114185; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 56423-63-3,Some common heterocyclic compound, 56423-63-3, name is 2-Bromopyrazine, molecular formula is C4H3BrN2, 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: A mixture of the respective pyrimidine halide derivative (II) (0.15 mmol), the respective boronic acid derivative (III) (0.18 mmol), and K2003 2M (0.3 mL, 0.6 mmol) in ethanol (3 mL) is purged with argon, tetrakis5 (triphenylphosphine)-palladium (0.0075 mmol) is added, and the RM is heated at 9000 overnight. Alternatively, thereaction can be performed in a microwave apparatus, at 120C for 15- 30 mm. The RM is filtered through a 0.45 um Glass MicroFiber filter, washed with EtOH/MeCN and DMF. The filtrate is purified either by preparative HPLC or FC. Alternatively, it is diluted with water, if needed the pH is adjusted, and extracted with EtOAc (3x). The combined organic extracts are dried (MgSO4) and concentrated under reduced pressure. The residue is purified by preparative HPLC or by FC. The title compound is prepared according to the general procedure A described above, using N-(2-(6-fluoro-4- methoxy-2-methyl-i H-indol-i -yl)ethyl)-6-(4-(4,4,5,5-tetramethyl-i ,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-4-amine and 4-chloro-6-methoxypyrimidine. LC-MS E: tR= 1.10 mm; [M+H]+ =484.88.

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

Reference:
Patent; ACTELION PHARMACEUTICALS LTD; FRETZ, Heinz; LYOTHIER, Isabelle; POTHIER, Julien; RICHARD-BILDSTEIN, Sylvia; SIFFERLEN, Thierry; WYDER PETERS, Lorenza; POZZI, Davide; CORMINBOEUF, Olivier; (306 pag.)WO2017/85198; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 181284-14-0,Some common heterocyclic compound, 181284-14-0, name is 3-Chloro-5-methylpyrazine-2-carbonitrile, molecular formula is C6H4ClN3, 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.

[00683] 3-Chloro-5-methylpyrazine-2-carbonitrile (1.1 g, 0.007 mol) was dissolved in anhydrous DMF (11 mL) and DIPEA (3.74 mL, 0.021 mol) was added. After stirring for 30 min at room temperature tert-butyl (4-methylpiperidin-4-yl)carbamate (1.84 g, 0.008 mol) was added in one portion. The reaction mixture was stirred overnight at room temperature, then diluted with EtOAc and extracted with 2% NaCl (aq.). The organic layer was dried over Na2SC4 and concentrated under reduced pressure. The desired product was purified via column chromatography (DCM/acetone 97:3) to yield tert-butyl N-[l-(3-cyano-6- methylpyrazin-2-yl)-4-methylpiperidin-4-yl]carbamate as a pale yellow solid (2.14 g, 90%). 1H MR (400 MHz, DMSO-i) delta 7.97 (s, 1H), 6.67 (bs, 1H), 3.96 (dt, J = 13.7, 4.3 Hz, 2H), 3.39 (dd, J = 13.4, 10.3 Hz, 2H), 2.42 (s, 3H), 2.15 (d, J = 13.4 Hz, 2H), 1.51 (ddd, J = 14.1, 10.6, 3.9 Hz, 2H), 1.40 (s, 9H), 1.27 (s, 3H).

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

Reference:
Patent; REVOLUTION MEDICINES, INC.; BLANK, Brian R.; PITZEN, Jennifer; WANG, Gang; WON, Walter S.; TZITZILONIS, Christos; LI, Jie Jack; KOLTUN, Elena S.; AAY, Naing; BUCKL, Andreas; MELLEM, Kevin; SEMKO, Christopher; JOGALEKAR, Ash; KISS, Gert; GILL, Adrian; (298 pag.)WO2018/136265; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 87597-21-5, 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. 87597-21-5, name is Ethyl 6,8-dibromoimidazo[1,2-a]pyrazine-2-carboxylate belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Method A6Preparation of Intermediate I-09. Intermediate I-07 (1.00 g, 2.87 mmol) was dissolved in DCM (28 mL) and N-bromosuccinimide (0.61 g, 3.44 mmol) and trifluoroacetic acid (0.25 mL) were added. The reaction mixture was stirring at rt for 16 h and then heated at 60 C. for 2 h more. The reaction mixture was cooled, and washed with water. The organic phase was dried (Na2SO4), filtered and the solvent removed in vacuum. The residue was purified by biotage with a gradient cyclohexane/EtOAc: from 100% to 50:50 The desired fractions were collected to obtained 1.15 g of a white solid as intermediate I-09 (Y: 94%).

The synthetic route of Ethyl 6,8-dibromoimidazo[1,2-a]pyrazine-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Centro Nacional De Investigaciones Oncologicas (CNIO); US2012/83492; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 313340-08-8, name is 3,5-Dichloro-6-ethylpyrazine-2-carboxamide, 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 313340-08-8, Application In Synthesis of 3,5-Dichloro-6-ethylpyrazine-2-carboxamide

General procedure: To a solution of compound6(0.4 mmol) and anappropriateaniline derivatives(0.2 mmol) in 1,4-dioxane, was added DIPEA (0.4 mmol). The mixture was stirred at 100oC for 12 h. The solution was diluted withwater, andfiltered. The residue was washed with water twice and dried to give the crude product as yellow solid in 42-74% yield.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Article; Wang, Yueliang; Xing, Li; Ji, Yinchun; Ye, Jiqing; Dai, Yang; Gu, Wangting; Ai, Jing; Song, Zilan; Bioorganic and Medicinal Chemistry Letters; vol. 29; 6; (2019); p. 836 – 838;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 875781-43-4, 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. 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: 2-Bromo-5H-pyrrolo[3,2-b]pyrazine(4; 0.471 g,2.39 mmol), 4-pyridylboronic acid (0.58 g, 4.72 mmol), dichloro 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloromethane adduct (0.097 g, 0.12 mmol), acetonitrile(3 mL) and 1M sodium carbonate (3 mL) were placed in a 10 mL CEM microwavevial. The vial was capped and irradiated in a CEM microwave reactor for 30minutes at 150 C.Water (3 mL) and ethyl acetate (9 mL) were added the layers were partitioned. Theaqueous layer was extracted with ethyl acetate (2 x 10 mL). The combined organicextracts were washed with saturated sodium chloride (5 mL), dried over MgSO4and concentrated under reduced pressure. The residue was purified by preparativereverse phase HPLC to give 2-(pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazine(14; 0.28 g,60%) as an off white solid: 1H NMR (400 MHz, DMSO-d6) delta 12.24 (s, 1H), 9.00(s, 1H), 8.69 (dd, J = 4.5, 1.6 Hz, 2H), 8.12 (dd, J = 4.5, 1.6Hz, 2H), 7.98 (d, J = 3.6 Hz, 1H), 6.74 (d, J = 3.6 Hz, 1H); ESMSm/z 197.1 (M+1).

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

Reference:
Article; Burdick, Daniel J.; Wang, Shumei; Heise, Christopher; Pan, Borlan; Drummond, Jake; Yin, Jianping; Goeser, Lauren; Magnuson, Steven; Blaney, Jeff; Moffat, John; Wang, Weiru; Chen, Huifen; Bioorganic and Medicinal Chemistry Letters; vol. 25; 21; (2015); p. 4728 – 4732;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, 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 36070-80-1, HPLC of Formula: C5H3ClN2O2

50 ml RBF was charged with 3-pentyn-2-ol (2.063 ml, 22.08 mmol) in DMF (10 ml) and potassium t-butoxide (1.24 g, 11.04 mmol) was added portionwise while stirring (cooling in water bath). The mixture was stirred at room temperature for 10 min until all t-BuOK went into solution, then 5-chloropyrazine-2-carboxylic acid (500 mg, 3.15 mmol) was added in portions and the resulting brown suspension was heated at 75 C. for 45 min. The mixture was cooled to room temperature and diluted with water (20 ml) until all solids dissolved, then acidified with 2M HCl solution (5.5 ml) to pH 2. The resulting solution was extracted with EtOAc, organic layer was washed with water twice then with brine, filtered through pad of celite and concentrated in vacuo. The resulting suspension was diluted with 3 ml heptane/EtOAc (20:1) mixture then filtered. The solid was washed with heptane and dried in vacuo to afford 5-(pent-3-yn-2-yloxy)pyrazine-2-carboxylic acid

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Chloropyrazine-2-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; WHITE, Ryan; ALLEN, Jennifer R.; EPSTEIN, Oleg; HONG, Fang-Tsao; HUA, Zihao; HUMAN, Jason Brooks; LOPEZ, Patricia; OLIVIERI, Philip R.; ROMERO, Karina; SCHENKEL, Laurie; STELLWAGEN, John; TAMAYO, Nuria A.; ZHENG, Xiao Mei; US2014/213581; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 1062608-42-7, name is 5-Bromo-3-iodopyrazin-2-amine, molecular formula is C4H3BrIN3, 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. Quality Control of 5-Bromo-3-iodopyrazin-2-amine

To a solution of 2b (4.0 g, 13.33 mmol) in 1,4-dioxane (55 mL) was added 3- (trifluoromethyl)phenyl boronic acid (6) (2.79 g, 14.67 mmol) followed by 1M aqueous solution of potassium carbonate (26.6 mL, 26.67 mmol) at RT. Reaction mixture was purged with N2 gas for 30 minutes. Bis(triphenylphosphine)palladium(II)chloride (0.65 g, 0.93 mmol) was added to the reaction mixture and was heated to reflux for 4 h, cooled to RT, filtered through celite. Filtrate was concentrated under vacuum to remove dioxane. 50 mL of water was added and extracted with dichloromethane. Organic layer combined and washed with water, dried over sodium sulfate and concentrated under vacuum. Crude product purified by flash chromatography using 30% ethyl acetate in petroleum ether to afford compound 3b (3.5 g, 83.3%) as pale yellow solid. 1H NMR (400 MHz, DMSO-d6): delta 8.14 (s, 1H), 7.90 (d, J = 8.40 Hz, 2H), 7.84 (d, J = 8.40 Hz, 2H), 6.63 (s, 2H). LC-MS APCI: Calculated for C11H7BrF3N3: 318.10; Observed m/z [M+H]+: 318.0.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1062608-42-7, its application will become more common.

Reference:
Patent; MMV MEDICINES FOR MALARIA VENTURE; UNIVERSITY OF CAPE TOWN; WATERSON, David; WITTY, Michael John; CHIBALE, Kelly; STREET, Leslie; GONZALEZ CABRERA, Diego; PAQUET, Tanya; (36 pag.)WO2017/9773; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem