Tag: M.W=100-200

Application 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.

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-carboxylic acid, its application will become more common.

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

These common heterocyclic compound, 14508-49-7, name is 2-Chloropyrazine, 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. SDS of cas: 14508-49-7

General procedure: A 10 mL round-bottom flask was charged with the prescribedamount of catalyst Pd/Cu, aryl chlorides (0.5 mmol), phenylboronicacids containing hydroxymethyl (0.75 mmol), Cs2CO3 (1.0 mmol)and dioxane (5 mL) in air. The reaction mixture was then placedin an oil bath and heated at 110 C for 24 h. After removal of thesolvent, the resulting residue was purified by flash chromatographyon silica gel using CH2Cl2 as eluent. The products 4a-k, and4m are known compounds [6,9] except for 4l and 4n.

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

Reference:
Article; Xu, Chen; Li, Hong-Mei; Wang, Zhi-Qiang; Fu, Wei-Jun; Inorganica Chimica Acta; vol. 423; 1; (2014); p. 11 – 15;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-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. HPLC of Formula: C6H7F3N4

VI (2.0g, 5.0mmol) and 3- (trifluoromethyl) -5,6,7,8-tetrahydro – [1,2,4] triazolo [4,3-a] pyrazine (of 0.912 g , 4.7mmol) Was dissolved in 20ml of anhydrous N, N- dimethylformamide was added HOBt (0.770g, 5.7mmol) and EDC ¡¤ HCl (1.092g, 5.7mmol), stirred at room temperature 20h. After the reaction was added 20ml of water and 20ml of ethyl acetate, there Phase was washed with water 3 times, washed three times with saturated aqueous sodium carbonate solution, the organic phase was dried over anhydrous sodium sulfate, suction filtered, and concentrated to give yellow Colored foamy solid 2.967g, crude yield> 100%, recrystallized from ethyl acetate, filtration and drying to give a yellow solid 1.827g, Recrystallization yield of 63.6%.

The synthetic route of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shanghai Institute Of Pharmaceutical Industry; China State Institute of Pharmaceutical Industry; Meng, Xiangguo; Cai, Zhengyan; Zhou, Weicheng; Jiang, Jingzhang; Zhu, Yijun; Ge, Yuanyuan; Yan, Pingping; (32 pag.)CN103172635; (2016); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 313339-92-3, name is 3,5-Dichloropyrazine-2-carbonitrile, 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 313339-92-3, SDS of cas: 313339-92-3

[00229] Step 1 : To a mixture of 3,5-dichloropyrazine-2-carbonitrile (68 mg, 0.39 mmol) in 2-methylpropan-2-ol (2 mL) was added tert-butyl l-amino-3-(methylthio)propan-2- ylcarbamate (50 mg, 0.23 mmol), Hunig’s base (101 mg, 0.780 mmol) under N2. The mixture was heated to 50 C under a 2 atmosphere for 5 hours. Upon cooling to 25 C, the mixture was diluted with brine (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organics were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (1: 1 petroleum ether/EtOAc) to afford tert-butyl l-(6-chloro- 5-cyanopyrazin-2-ylamino)-3-(methylthio)propan-2-ylcarbamate as a solid. MS ESI calc’d. for Ci4H21ClN502S [M + H]+ 358, found 358. XH NMR (400MHz, DMSO-d6) delta 7.80 (s, 1H), 6.84 (s, 1H), 5.06 (s, 1H), 3.99 – 3.93 (m, 1H), 3.64 – 3.51 (m, 2H), 2.68 – 2.67 (m, 2H), 2.13 (s, 3H), 1.38 (s, 9H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,5-Dichloropyrazine-2-carbonitrile, and friends who are interested can also refer to it.

Reference:
Patent; MERCK SHARP & DOHME CORP.; ALTMAN, Michael, D.; CASH, Brandon; ELLIS, John Michael; MADDESS, Matthew, L.; NORTHRUP, Alan, B.; OTTE, Ryan, D.; SUN, Binyuan; WO2015/138273; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 4774-14-5, 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. 4774-14-5, name is 2,6-Dichloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

(1) Synthesis of 2-benzyloxy-6-chloropyrazine as an intermediate: 7.6 g of benzylalcohol was dissolved in 65 ml of benzene, and 2.8 g of 60% sodium hydride was added little by little to the solution under stirring not so as to foam too much at room temperature. After the addition, stirring was continued for 10 min. at room temperature, followed by reflux for 1 hour. Subsequently, the solution was cooled to 50 to 60 C., and added dropwise with a solution of 10 g of 2,6-dichloropyrazine in 65 ml of benzene for 10 min. Then, after reflux for 4 hours, the reaction was finished. After cooling below 10 C., about 100 ml of water was added, and the separated benzene layer was collected. The residue obtained by distilling off the solvent was purified by silica-gel column chromatography (developing solvent: n-hexane and ethyl acetate) to obtain 12.8 g of 2-benzyloxy-6-chloropyrazine as a colourless oil (yield: 86.5%) nD25 1.5818.

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, 2,6-Dichloropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Nippon Kayaku Kabushiki Kaisha; US4791127; (1988); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

6863-73-6, name is 3-Chloropyrazin-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. COA of Formula: C4H4ClN3

3-chloropyrazine-2-amine (1.29 g, 10 mmol)And chloroacetaldehyde (40% aqueous solution, 9.8 g, 50 mmol) were added to 30 mL of isopropanol, and heated under reflux overnight.The solvent was removed by rotary evaporation, and 30 mL of water was added to dissolve.Adjust pH = 7 with saturated sodium bicarbonate solution, extract with ethyl acetate (20mL * 3), combine the organic phases,It was washed with 20 mL of saturated brine, dried over anhydrous sodium sulfate, and concentrated.1.07 g of a pale yellow solid was isolated through a silica gel column with a yield of 70%.

The synthetic route of 6863-73-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shenzhen Tajirui Bio-pharmaceutical Co., Ltd.; Wang Yihan; Xing Qingfeng; Ai Yixin; (85 pag.)CN110272426; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route 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.

2,3-dichloropyrazine (III-9) (500 mg, 3.36 mmol) and 4-chlorophenol (II-17)(431 mg, 3.36 mmol) was dissolved in DMF (10 mL)Potassium carbonate (557 mg, 4.03 mmol) was added,Followed by stirring at 90 C. for 15 hours. The reaction solution was cooled,Water was added and extracted with ethyl acetate.The organic layer was washed successively with water and saturated brine,The solvent was distilled off under reduced pressure.The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 100: 0 ? 85: 15) to obtain compound (IV-102)(Yield 809 mg, yield quantitative)As a white solid.

The synthetic route of 4858-85-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Kaken Pharmaceutical Co., Ltd.; Watanabe, Atsushi; Sato, Yuki; ogura, Keiji Tamada; Tatsumi, Yoshiyuki; (283 pag.)JP2018/145180; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 55557-52-3, 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. 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows.

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.

The chemical industry reduces the impact on the environment during synthesis 3-Chloropyrazine-2-carbonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Article; Fresneau, Nathalie; Cailly, Thomas; Fabis, Frederic; Bouillon, Jean-Philippe; Tetrahedron; vol. 69; 26; (2013); p. 5393 – 5400;,
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. COA of Formula: C9H16N2O2

DMSO (1.95 g, 1.64 mL, 25.0 mmol) was added dropwise to a solution of oxalyl chloride (1.52 g,1.05 mL, 12.0 mmol) in CH2Cl2 at -78 0C. After stirring at -78 0C for 15 min, 4-phenyl-l-butanol (1.50 g, 1.52 mL, 10.0 mmol) was added dropwise. After 15 min, triethylamine (5.05 g, 6.96 mL) was added dropwise. After warming to r.t. over 2 hours, water (50 mL) was added and the solution was extracted with CH2Cl2 (4 X 50 mL). The combined organic phase was washed with HCl (0.25 N, 3 X 50 mL), water (50 mL), saturated NaHCO3, and brine. The organic extract was dried over Na2SO4, concentrated, and passed through a short silica column (2 x 3 cm), eluted with CH2Cl2. Solvent was removed to give 4-phenylbutanal as a colorless oil (1.30 g, 87percent). 1H NMR (500 MHz, CDCl3) delta 9.76 (t, / = 1.5 Hz, 1 H), 7.31-7.27 (m, 2 H), 7.22-7.17 (m, 2 H), 2.67 (t, / = 7.5 Hz, 2 H), 2.46 (dt, J = 1.6, 7.32 Hz, 2 H), 1.97 (m, 2 H).[000199] To a solution of the bislactim (R)-2-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (1.842 g, 1.792 mL, 10.0 mmol) in THF (20 mL) at -78 0C was slowly added n-BuLi (6.875 mL, 1.6 M in hexanes, 11.0 mmol) under Ar. After stirring at -78 0C for 20 min, A methyl iodide solution (1.562 g, 0.686 mL, 11.0 mmol) in THF (5 mL) was added. It was stirred at -78 0C for 2 h. A further portion of n-BuLi (6.25 mL, 1.6 M in hexanes, 10.0 mmol) was added at -78 0C and the solution was warmed to 0 0C. A solution of SnCl2 (1.0 g, 5.3 mmol) in THF (20 mL) was added and stirred at 0 0C for 15 min. After cooling to -78 0C, a 4-phenylbutanal solution (0.74 g, 5.0 mmol) was added. After the mixture was stirred at -78 0C for 3 h, it was warmed to r.t. and a phosphate buffer (pH 7.0, 0.10 M, 150 mL) was added with stirring for an additional 10 min. The mixture was filtered and the solid washed with ether. The aqueous phase was extracted with ether (3 X 50 mL) and the combined organic phase was washed with brine and dried over Na2SO4. Solvent was removed and the residue was purified by silica gel column chromatography (3 X 25 cm, hexanes: EtOAc 9:1) to give compound 65 as a colorless viscous oil (850mg, 49percent). 1H NMR (500 MHz, CDCl3) delta 7.28-7.25 (m, 2 H), 7.19-7.15 (m, 3 H), 3.94 (d, / = 3.5 Hz, 1 H), 3.70 (s, 3 H), 3.64 (s, 3 H), 3.59 (dt, J = 2.0, 10.3 Hz, IH), 2.66-2.60 (m, 2 H), 2.28-2.25 (m, 1 H), 1.99 (d, J = 10.0 Hz, 1 H), 1.95-1.85 (m, I H), 1.75-1.65 (m, I H), 1.60-1.52 (m, 1 H), 1.35 (s, I H), 1.33-1.23 (m, 1 H), 1.08 (d, / = 7.0 Hz, 3 H), 0.69 (d, / = 6.9 Hz, 1 H). ESIMS (MNa+) m/z 369.4.[000200] Compound 65 (692 mg, 2.0 mmol) is dissolved in acetonitrile (24 mL) containing HCl (0.50 M, 24 mL). After the mixture is stirred at r.t. for 12 h, the solvent is removed, the residue is dissolved in a NaOH solution (2.0 M, 20 mL) in MeOH (2OmL), and the progress of the reaction is monitored by TLC. The reaction mixture was neutralized with a solution of HOAc, and solvent is removed. The residue is purified by reverse phase HPLC to give desired product, compound 66, as an amorphous white solid.

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; FORBES MEDI-TECH (RESEARCH), INC.; WO2008/31032; (2008); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 54013-06-8, name is Ethyl 5-aminopyrazine-2-carboxylate, 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 54013-06-8, name: Ethyl 5-aminopyrazine-2-carboxylate

A mixture of aminopyrazine, 3-bromo-1,1,1-trifluoropropan-2-one and ethanol was heated in a microwave synthesizer at 180 C for 60 minutes. After cooling to room temperature, the solvent is removed and the dark brown residue is purified by flash chlromatography (silica, 30-60% ethyl acetate/hexanes) to give I-3 as a tan colored solid. 1H NMR (400 MHz, CDCI3) delta 9.24 (s, 1H), 8.99 (d, J= 1.4, 1H), 8.10 (s, 1H), 4.51 (q, J= 7.1, 2H), 1.46 (t, J= 7.1, 3H).

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:
Patent; IRM LLC; NOVARTIS AG; CHATTERJEE, Arnab Kumar; NAGLE, Advait Suresh; PARASELLI, Prasuna; LEONG, Seh Yong; ROLAND, Jason Thomas; MISHRA, Pranab Kumar; YEUNG, Bryan KS; ZOU, Bin; WO2014/78813; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem