Tag: M.W=100-200

Electric Literature of 5521-58-4, These common heterocyclic compound, 5521-58-4, name is 5-Methylpyrazin-2-amine, 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.

Examples (2R)-2-(3-Chloro-4-cyclopropanesulfonylphenyl)-3-(tetrahydropyran-4-yl)propionic acid (Preparation 9) was coupled with amines selected from 2-amino-5-methylpyrazine, 3- amino-5-methylisoxazole, 3-aminoisoxazole, 2-amino-5-methylthiazole, 3-amino-6- methylpyridazine, l-methyl-3-aminopyrazole, 2-aminopyrazine and 4-aminopyrimidine using the following procedure to provide Examples 1-8.CH2Cl2 (6OmL) and DMF (0.08mL, 1.064mmol, 1.2 eq) were cooled to -100C and oxalylchloride slowly added (0.09mL, 0.465mol, 1.2 eq). After stirring for 15 min the reaction mixture was cooled to -300C and (2R)-2-(4-cyclopropanesulfonylphenyl)-3- (tetrahydropyran-4-yl)propionic acid (Preparation 8, 0.300g, 0.886mmol, 1.0 eq) was added.The reaction was stirred at -300C for 45min then pyridine (1.395mol, 0.3ImL in ImL CH2Cl2, 4.5eq) and the amine (4.43mmol, 5.0eq) were slowly added in parallel at -400C. The reaction mixture was stirred for 15min then the ice bath removed. The reaction mixture was stirred for 2h until it reached rt. The solvent was removed under partial vacuum and the crude mixture dissolved in EtOAc (1OmL) and aqueous HCl (1.5mL). The layers were separated and the aqueous phase extracted with EtOAc (5mL). The organic fractions were combined and washed with H2O (1OmL), saturated aqueous NaHCO3 (2 x 1OmL), water (5mL) and brine (5mL) and dried (MgSOzi). Purification was by flash chromatography (EtOAc :heptane, 2:1) and/or recrystallisation.

Statistics shows that 5-Methylpyrazin-2-amine is playing an increasingly important role. we look forward to future research findings about 5521-58-4.

Reference:
Patent; PROSIDION LTD; WO2007/51846; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 27398-39-6, 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. 27398-39-6 name is 3-Chloropyrazine-2-carboxylic acid, 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.

To a solution of 3-chloropyrazine-2-carboxylic acid (100 mg, 0.63 mmol) in DCM/MeOH (2 mL : 0.2 mL) was added TMSCH1?2 (0.47 mL, 0.95 mmol) at RT and the resulting mixture was stirred at RT for 2 h. Acetic acid (0.2 mL) was added and the mixture was 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. LRMS m/z (M+H) 173.0 found, 173.0 required.

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

Reference:
Patent; MERCK SHARP & DOHME CORP.; KIM, Ronald; KUDUK, Scott, D.; LIVERTON, Nigel; ZHUO, Gang; (97 pag.)WO2016/100157; (2016); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 1174321-06-2, 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. 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

General Procedure A: the coupling of anilines prepared in Preparation Examples 25- (14) and 26-Q2) with aryl carboxylic acidsThe aniline (100 mg) was dissolved in DCM (2 mL) and the aryl carboxylic acid (1.2 – 1.6 equiv.), N,N-diisopropylethylamine (3 equiv.) and (lH-benzotriazol-1- yloxy)tripyrrolidin-l-yl)phosphonium hexafluorophophate (1.2 – 1.6 equiv.) were added. The reaction mixture was stirred at RT for 16 h – 3 days, and sodium bicarbonate (sat., aq., 25 mL) was added. The mixture was extracted with EtOAc (2 x40 mL), the combined organic portions were dried over MgSO4, evaporated and purified by silica gel chromatography (EtOAc/hexanes gradient) to afford the amide as a white solid. The amide was dissolved in DCM (2 mL) and TFA (1 mL) was added. After stirring at RT for 1-3 h, the reaction mixture was evaporated and sodium bicarbonate (sat., aq., 25 mL) was added. The mixture was extracted with EtOAc (2 x 40 mL), and the combined organic portions dried over MgSO4 and evaporated to afford the desired compound as a white solid. On occasions where the product was not pure, purification was effected by silica gel chromatography (MeOH/EtOAc/DCM gradients). Example 1 : N-(3-((‘4aR,5S,7aS)-2-amino-5-(‘fluoromethyl)-4a,5,7,7a-tetrahvdro-4H- furor3,4-diri,31oxazin-7a-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2- carboxamideSynthesized from tert-butyl [(4aR,5S,7aS)-7a-(5-amino-2-fluorophenyl)-5- fluoromethyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][l,3]oxazin-2-yl]carbamate 25-(14) and 5-difluoromethyl-pyrazine-2-carboxylic acid according to General Procedure A. 1H NMR (400 MHz, CDCl3) delta (ppm): 2.94 (d, /=7.8 Hz, IH), 3.79 (dd, /=8.6, 2.5 Hz, IH), 3.89 – 4.05 (m, 2H), 4.28 – 4.66 (m, 4H), 6.72 (t, J 54.3 Hz, IH), 7.05 (dd, /=11.6, 8.8 Hz, IH), 7.67 (dd, /=7.1, 2.8 Hz, IH), 7.91 – 8.03 (m, IH), 8.85 (s, IH), 9.45 (s, IH), 9.61 (br s, IH)

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-(Difluoromethyl)pyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; EISAI R&D MANAGEMENT CO., LTD; ELLARD, John Mark; FARTHING, Christopher Neil; HALL, Adrian; WO2011/9898; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 23688-89-3, A common heterocyclic compound, 23688-89-3, name is 6-Chloropyrazine-2-carboxylic acid, molecular formula is C5H3ClN2O2, 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.

6-Chloro-N-cyclobutylpyrazine-2-carboxamide: To a suspension of 6-chloropyrazine-2-carboxylic acid (100 mg, 0.631 mmol), HATU (288 mg, 0.757 mmol), and cyclobutanamine (49 mg, 0.69 mmol) in DMF (1.26 mL) at 0 C was added DIEA (220 pi, 1.26 mmol) and the resulting mixture was stirred at rt for 2 h. The volatiles were removed under reduced pressure. The residue was purified via silica gel chromatography (0 – 100 % EtOAc in hexanes) to give the title compound (84 mg, 63%) as an off-white solid. MS (ES+) C9H,0C1N30 requires: 211, found: 212 [M+Hf?. ?H NMR (600 MI-Tz, Chloroform-d) oe 9.28 (s, 1H), 8.75 (s, 1H), 7.72 (s, 1H), 4.66 – 4.53 (m, 1H), 2.50 – 2.38 (m, 2H), 2.13 – 1.98 (m, 2H), 1.87- 1.73 (m, 2H)

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; TESARO, INC.; JONES, Philip; CZAKO, Barbara; BURKE, Jason P.; CROSS, Jason; LEONARD, Paul Graham; (208 pag.)WO2018/81276; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 486460-21-3,Some common heterocyclic compound, 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, molecular formula is C6H7F3N4, 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.

Dichloromethane (100 ml) and the keto acid compound (10.0 g, 43.07 mmol) prepared in Example 8 were added to a 250 ml three-necked flask, and dissolved by stirring. Oxalyl chloride (6.56 g, 51.68 mmol) was added dropwise at 10 to 15 C, and the dropwise addition was completed, and the mixture was heated to 30 to 35 C to stir the reaction. The reaction was completed, and concentrated under reduced pressure at 30 to 40 C to dryness to pale-yellow liquid (10.91 g, 43.64 mmol), methylene chloride (100 ml), triethylamine (5.79 g, 57.24 mmol) and the above yellow liquid (10.0 g, 52.04 mmol) was dissolved by stirring. The solution of the free base (13.0 g, 52.04 mmol) / dichloromethane (20 ml) of the compound of the formula a was added dropwise to 0 to 5 C, and the dropwise addition was completed. After the completion of the dropwise addition, the mixture was heated to 10 to 15 C to stir the reaction. The reaction was completed, water was added and stirred. Layering, taking the lower organic phase and discarding the upper aqueous phase. The organic phase was washed with a 5% aqueous solution of sodium chloride and concentrated to dryness to dryness to dryness to afford white solid (19.24 g, 47.36 mmol) as a ketoamide compound in a molar yield of 91%.

The synthetic route of 486460-21-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zhejiang Ruibo Pharmaceutical Co., Ltd.; Gao Zhaobo; Zhang Xianyi; He Zhi; Mei Yijiang; Zheng Hui; (9 pag.)CN109956865; (2019); A;,
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 6863-73-6 as follows. Recommanded Product: 6863-73-6

[0665] A 3-necked 250 mL round-bottomed flask was charged with cesium carbonate (22.64 g, 69.5 mmol), 2-amino-3-chloropyrazine (3 g, 23.16 mmol, Synchem Inc., Elk Grove Village, IL), and {1,1′-bis(diphenylphosphino)ferrocene} dichloropalladium(II) (1.69 g, 2.32 mmol, Strem Chemicals, Newburyport, MA). A reflux condenser was attached, and the apparatus was sealed. The vessel was evacuated and backfilled with nitrogen. DMF (66.2 mL) was added, followed by triethylborane (1.0 M in THF; 42 mL, 42 mmol; Sigma-Aldrich Corporation, St. Louis, MO, USA). The reaction was then stirred in a pre-heated 90 C oil bath for 1 h. The reaction mixture was cooled to rt, water was added, and the resulting mixture was extracted with DCM (2). The combined extracts were dried over MgSO4 and concentrated in vacuo. The crude residue was taken up in MeOH and loaded onto a column composed of Si- propylsulfonic acid (Silicyle). The column was flushed with 4 column volumes of MeOH before eluting the title compound with 4 column volumes of 2M ammonia in MeOH. The filtrate was concentrated in vacuo, and the residue was purified by silica gel chromatography (eluent: 0-20% 2 M NH3 in MeOH/DCM) to provide 3-ethylpyrazin-2-amine (Intermediate I- 19, 2.34 g, 19.0 mmol, 82 % yield) as a brown oil. 1H NMR (400 MHz, DMSO-d6) d ppm 7.75 (d, J=2.70 Hz, 1H) 7.65 (d, J=2.70 Hz, 1H) 6.13 (br s, 2 H) 2.60 (q, J=7.39 Hz, 2 H) 1.17 (t, J=7.46 Hz, 3 H).

According to the analysis of related databases, 6863-73-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AMGEN INC.; ALLEN, John Gordon; ALLEN, Jennifer Rebecca; MINATTI, Ana Elena; XUE, Qiufen; WURZ, Ryan Paul; TEGLEY, Christopher M.; PICKRELL, Alexander J.; NGUYEN, Thomas T.; MA, Vu Van; LOPEZ, Patricia; LIU, Longbin; KOPECKY, David John; FROHN, Michael J.; CHEN, Ning; CHEN, Jian Jeffrey; SIEGMUND, Aaron C.; AMEGADZIE, Albert; TAMAYO, Nuria A.; BOOKER, Shon; GOODMAN, Clifford; WALTON, Mary; NISHIMURA, Nobuko; SHIN, Youngsook; LOW, Jonathan D.; CEE, Victor J.; REED, Anthony B.; WANG, Hui-Ling; LANMAN, Brian Alan; (738 pag.)WO2019/213516; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 59489-71-3, 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. 59489-71-3, name is 2-Amino-5-bromopyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Into a 20-L 4-necked round-bottom flask was placed a solution of 5-bromopyrazin-2-amine (400 g, 2.30 mol) in ethylene glycol dimethyl ether (8 L) , iodocopper (131 g, 687.84 mmol) , diiodane (293 g, 1.15 mol) , iodopotassium (380 g, 2.29 mol) and 3-methylbutyl nitrite (1800 mL, 11.5 mol) . The resulting solution was stirred for 30 min at 60 C, then extracted with 2 x 10 L of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum to afford the title compound.

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-Amino-5-bromopyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK SHARP & DOHME CORP.; DEBENHAM, John S.; COX, Jason M.; LAN, Ping; SUN, Zhongxiang; FENG, Zhe; SUN, Chunrui; SEGANISH, W. Michael; LAI, Zhong; ZHU, Chen; BARA, Thomas; RAJAGOPANALAN, Murali; DANG, Qun; KIM, Hyunjin M.; HU, Bin; HAO, Jinglai; (112 pag.)WO2018/107415; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, 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. Formula: C5H4N4

To a suspension of 5-aminopyrazine-2-carbonitrile (211 mg, 1.74 mmol) in THF (10 mL) was added sodium hydride (116 mg, 2.90 mmol) at 0 C and stirred at ambient temperature for 1 h. Compound 305-7 (500 mg, 1.45 mmol) was added and stirred at 55 C for 2 h. After cooling to ambient temperature, the reaction mixture was quenched with ice-water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over Na2SO4 and concentrated. The crude product was purified by column chromatography (hexanes/ethyl acetate: 5/1) to afford the title compound 306-7 as a yellow solid (253 mg, 42 % yield).

The synthetic route of 5-Aminopyrazine-2-carbonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PHARMAENGINE, INC.; CAI, Xiong; QIAN, Changgeng; WANG, Yanong Daniel; (98 pag.)WO2017/132928; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 19847-12-2, 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. 19847-12-2, name is Pyrazinecarbonitrile, This compound has unique chemical properties. The synthetic route is as follows.

Step 6 C-Pyrazin-2-yl-methylamine Pyrazine-2-carbonitrile 1g (10.5 g, 100 mmol) was dissolved in 150 mL of 1,4-dioxane, then Raney nickel (1.0 g) was added into a 250 mL autoclave. The reaction mixture was reacted in hydrogen atmosphere for 8 hours under 40 atmosphere at 60 C and filtered and concentrated under reduced pressure to obtain the title compound C-pyrazin-2-yl-methyl amine 1h (10.7 g, yield 98%) as a brown oil. MS m/z (ESI): 110 [M+1].

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

Reference:
Patent; Jiangsu Hengrui Medicine Co., Ltd.; Shanghai Hengrui Pharmaceutical Co. Ltd.; EP2404921; (2012); 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. 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, A new synthetic method of this compound is introduced below., COA of Formula: C5H2ClN3

A mixture of the respective boronic acid derivative (B-B(OH)2) (21.5 mmol), 3-chloro-pyrazine-2-carbonitrile (21.5 mmol), a solution of K2CO3 (59.4 mmol) in water (30 mL), PPh3 (3. 2 mmol), Pd(OAc)2 (1.05 mmol) in dry DME was stirred at reflux under inert atmosphere for 16 h. After cooling to rt, the reaction mixture was diluted with EtOAc, filtered over celite, the filtrate was dried over MgSO4, filtered and concentrated in vacuo to yield the desired pyrazine-2-carbonitrile derivative which was used for the next step without further purification prepared by reaction with commercially available 3-m-tolyl-boronic acid LC-MS: tR=0.88 min; [M+H+ MeCN]+=243.63

The synthetic route of 55557-52-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Aissaoui, Hamed; Boss, Christoph; Hazemann, Julien; Koberstein, Ralf; Siegrist, Romain; Sifferlen, Thierry; US2011/105491; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem