Author: Jessica.F

Adding a certain compound to certain chemical reactions, such as: 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-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 6966-01-4, Recommanded Product: Methyl 3-amino-6-bromopyrazine-2-carboxylate

(4-(5-(5-Amino-6-(5-tert-butyl- 1 ,3,4-oxadiazol-2-yl)pyrazin-2-yl)- 1 -methyl- 1H- 1 ,2,4- triazol-3 -yl)piperidin- 1 -yl)-3 -(tetrahydro-2H-pyran-2-yloxy)propan- 1 -one (Example 2.1) was prepared as follows: Hydrazine hydrate (23.59 mL, 480.75 mmol) was added dropwise to a stirred mixture of methyl 3-amino-6-bromopyrazine-2-carboxylate (100 g, 418.04 mmol) in EtOH (2 L). The mixture was heated at 50C under nitrogen. The resulting thick suspension was stirred at 50 C for 16 hours. Further hydrazine (2.5 mL) was added in one portion and the suspension was stirred at 50 C for a further 24 hours. Ethanol (500 mL) was charged to the thick reaction mixture and the mixture was allowed to cool to room temperature. The resulting suspension was filtered and the solid washed with ethanol (1 L) and dried in vacuo to give 3-amino-6-bromopyrazine-2-carbohydrazide (98 g, quantitative) as a cream solid: 1H NMR Spectrum: (DMSO-d6) 4.52 (2H, s), 7.59 (2H, s), 8.30 (1H, s), 9.74 (1H, s); Mass Spectrum [M+H]+ = 232.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-amino-6-bromopyrazine-2-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BARLAAM, Bernard Christophe; BERRY, David; DELOUVRIE, Benedicte; HARRIS, Craig Steven; LAMBERT-VAN DER BREMPT, Christine Marie Paul; OUVRY, Gilles; REID, Gary Patrick; TOMKINSON, Gary Peter; WO2014/114928; (2014); 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. 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., name: Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate

A mixture of methyl 3-amino-5,6-dichloropyrazine-2-carboxylate (1.00 g, 4.50 mmol), (4-methylphenyl)boronic acid (0.612 g, 4.50 mmol), sodium carbonate (0.955 g, 9.01 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complexed with dichloromethane (1:1) (0.18 g, 0.22 mmol) in 1,4-dioxane (18 mL) and water (2 mL) was evacuated then refilled with nitrogen. The resulting mixture was stirred at 90 C. for 2 h. The mixture was cooled to room temperature then (4-cyanophenyl)boronic acid (0.66 g, 4.50 mmol) was added, followed by another portion of [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II) complexed with dichloromethane (1:1) (0.2 g, 0.2 mmol). The vessel containing the mixture was evacuated then refilled with nitrogen and stirred at 90 C. for additional 2 h. The reaction mixture was cooled to room temperature and diluted with methylene chloride, washed with water and brine. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified on a silica gel column eluting with 0 to 25% EtOAc/DCM to give the desired product (1.2 g, 77%). LC-MS calculated for C20H17N4O2 (M+H)+: m/z=345.1. found 345.1.

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 1458-18-0.

Reference:
Patent; Incyte Corporation; Wu, Liangxing; Courter, Joel R.; He, Chunhong; Li, Jingwei; Lu, Liang; Sun, Yaping; Wang, Xiaozhao; Yao, Wenqing; Zhang, Colin; Zhuo, Jincong; (87 pag.)US2016/9720; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 33332-28-4, name is 2-Amino-6-chloropyrazine, 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 33332-28-4, Quality Control of 2-Amino-6-chloropyrazine

Example 27; Synthesis of N-(6-chloropyrazin-2-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide; Step 1; Phenyl 6-chloropyrazin-2-ylcarbamate; A solution of 2-amino-6-chloropyrazine (2.0 g, 15.44 mmol) in a mix of 1:1 THF:MeCN (20 mL), and pyridine (1.28, 16.2 mmol) was treated dropwise with phenylchloroformate (2.54 g, 16.2 mmol) in THF (10 mL). After stirring for 18 h, the resulting solid was collected and dried to provide the title compound (2 g, 53percent).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Amino-6-chloropyrazine, and friends who are interested can also refer to it.

Reference:
Patent; FAY, Lorraine Kathleen; Johnson, Douglas S.; Kesten, Suzanne Ross; Lazerwith, Scott E.; Morris, Mark Anthony; Stiff, Cory Michael; Meyers, Marvin Jay; Wang, Lijuan Jane; US2008/261941; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 762240-92-6, The chemical industry reduces the impact on the environment during synthesis 762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, I believe this compound will play a more active role in future production and life.

Example 4 Synthesis 7-chloroacetyl-3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine of formula (VIII, Q = chlorine) 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride (54.6 g, 239 mmol) is suspended in ethyl acetate (300 ml) and added, under strong stirring, with a 30% NaOH solution (100 g) and water (50 ml). After 10 minutes the phases are separated, the aqueous phase is extracted with 3×70 ml of ethyl acetate and the organic phase is dried with Na2SO4, then filtered and the solvent is evaporated off under reduced pressure to obtain a white solid (45.4 g, 236 mmol, 99% yield).

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-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Dipharma Francis S.r.l.; EP2270009; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 55557-52-3, A common heterocyclic compound, 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, molecular formula is C5H2ClN3, 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 1.50 g (10.75 mmol, 1 equiv) of 2 chloro-3-cyanopyrazine 15 in propanenitrile (10 mL) was added 3.30 g (21.50 mmol, 2 equiv) of bromotrimethylsilane dropwise, and the resulting mixture was stirred for 16 h at room temperature. Subsequently, the reaction mixture was cooled to 0 C and quenched with an aqueous solution of 2 M NaOH (10 mL). Afterward, the aqueous phase was extracted with EtOAc (3¡Á10 mL), and the combined organic phases were washed with brine (2¡Á10 mL). After drying (MgSO4) and evaporation of the solvents in vacuo, the product was recrystallized from Et2O to afford 1.56 g (8.49 mmol, 79% yield) of 3-bromo-2-cyanopyrazine 16 as white crystals (mp=43.5 C). 1H NMR (CDCl3): delta 8.61 (1H, d, J=2.2 Hz, CH); 8.71 (1H, d, J=2.2 Hz, CH). 13C NMR (CDCl3): delta 114.7 (CN); 133.3 (CCN); 143.3 (CBr); 143.4 (CH); 147.0 (CH). IR (ATR, cm-1): nu=3101; 2243 (CN); 1958; 1538; 1515; 1425; 1364; 1336; 1249; 1184; 1161; 1071; 1048; 945; 870; 839; 824; 668; 653. GC-MS (EI) m/z (%): 183/185 (M+, 58); 129/131 (13); 104 (M+-Br, 100); 77 (23); 52 (28). Anal. Calcd for C5H2BrN3: C, 32.64; H, 1.10; N, 22.84. Found: C, 32.78; H, 1.15; N, 22.67.

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:
Article; Piron, Karel; Kenis, Sara; Verniest, Guido; Surmont, Riccardo; Thuring, Jan Willem; Ten Holte, Peter; Deroose, Frederik; De Kimpe, Norbert; Tetrahedron; vol. 68; 34; (2012); p. 6941 – 6947;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 98-97-5, name is Pyrazine-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 98-97-5, name: Pyrazine-2-carboxylic acid

To a solution of Pyrazine-2-carboxylic acid (295mg, 2. [1MMOL,] leq) and triethylamine [(765UL,] 5.4mmol, 2.6eq) in THF (6ml) at [0 C] was added dropwise diphenylphophoryl azide [(L.] 4ml, 2. [8MMOL,] [1.] 3eq). The mixture was stirred under nitrogen at [0 C] for 30 minutes, then warmed to RT and stirring continued for a further 2 hours. The reaction mixture was concentrated under vacuum and purified by flash chromatography [(90/10-60/40] [ISO-HEXANE/ETOAC)] to afford the title compound as white solid (265mg, yield=78%). 1H NMR (400 MHz, [CDC13)] [6] 9.14 (d, 1H, J=1.2) ; 8.50 (dt, 1H, J=1.2, 0.4), 2.62 (s, 3H, broad).

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; MILLENIUM PHARMACEUTICALS, INC.; WO2003/101444; (2003); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 622392-04-5, A common heterocyclic compound, 622392-04-5, name is 2-Bromo-5-iodopyrazine, molecular formula is C4H2BrIN2, 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 2-bromo-5-iodopyrazine (CAS 622392-04-5) (250 mg, 878 muiotaetaomicron) in 0.7 ml of pyridine, was added 2-methylpropane- 1,2-diamine (116 mg, 138 mu, 1.32 mmol, 1.5 equiv.) at room temperature. The colorless solution was stirred for 16 hours at 100C. The reaction mixture was cooled and concentrated in vacuo. The crude material was used directly in the next step.

The synthetic route of 622392-04-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GREEN, Luke; GUBA, Wolfgang; JAESCHKE, Georg; JOLIDON, Synese; LINDEMANN, Lothar; RICCI, Antonio; RUEHER, Daniel; STADLER, Heinz; VIEIRA, Eric; WO2011/128279; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 1458-16-8, 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. 1458-16-8, name is Methyl 3-amino-6-iodopyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

30 ml of ammonia in water is added under magnetic stirring to 15 g (53.8 mmol) of a solution of methyl 3-amino-6-iodopyrazine-2-carboxylate in 150 ml of methanol. The reaction medium is stirred at 25C for 48 hours. After evaporation of the solvents, the precipitate obtained is filtered, rinsed with water and then dried at 50C to yield 12.50 g of 3-amino-6-iodopyrazine-2-carboxamide (88%) in the form of a beige solid. LCMS (EI, m/z): (M+1) 265.02 1H NMR: deltaH ppm (400 MHz, DMSO): 8.35 (1H, s, CHarom), 7.85 (1H, bs, NH), 7.60 (3H, bs, NH), 3.25 (3H, s, CH3)

The chemical industry reduces the impact on the environment during synthesis Methyl 3-amino-6-iodopyrazine-2-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; PIERRE FABRE MEDICAMENT; Sokoloff, Pierre; Cachoux, Frederic; EP2689778; (2014); 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. 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, A new synthetic method of this compound is introduced below., Application In Synthesis of 5-Chloropyrazine-2-carboxylic acid

Step 1: 5-chloro-N-[l-(trifluoromethyl)cyclopropyl]pyrazine-2-carboxamideN,N-Diisopropylethylamine (1.3 niL, 7.5 mmol) was added to a mixture of 5- chloropyrazine-2-carboxylic acid (0.40 g, 2.5 mmol), N,N,N’,N’-tetramethyl-0-(7- azabenzotriazol-l-yl)uronium hexafluorophosphate (1.0 g, 2.8 mmol) and 1- (trifluoromethyl)cyclopropanamine (0.32 g, 2.5 mmol) (Oakwood, Cat.No.: 038175) in dichloromethylene (10 mL). The reaction mixture was stirred at room temperature overnight. The reaction mixture was worked up with saturated aqueous NaHCCh, and extracted with ethyl acetate (3 x 20 mL). The combined organic layers were washed with brine, dried over MgS04, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-20%) to afford the desired product (0.41 g, 67%). LCMS (M+H) +: m/z = 266.0/267.9.

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; INCYTE CORPORATION; YAO, Wenqing; BURNS, David M.; ZHUO, Jincong; WO2012/177606; (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. 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, A new synthetic method of this compound is introduced below., Application In Synthesis of (3-Chloropyrazin-2-yl)methanamine hydrochloride

To a solution of 3-isopropyl-3- (methoxycarbonyl) cyclohexanecarboxylic acid (4.4 g, 19.3 mmol) in THF (100 mL) was added (3-chloropyrazin-2-yl) methanamine hydrochloride (5.2 g, 28.9 mmol) , HATU (11 g, 28.9 mmol) and TEA (11.7 g, 115.8 mmol) . The mixture was stirred at room temperature overnight. The reaction mixture was diluted with EA and water, the organic layer was dried and concentrated. The residue was purified by column chromatography on silica gel eluted with PE/THF 5/1 to give methyl 3- ( ( (3-chloropyrazin-2-yl) methyl) carbamoyl) -1-isopropylcyclohexanecarboxylate. 1H NMR (400 MHz, CDCl3) delta ppm: 0.86 (t, J 6.65 Hz, 6 H) , 1.16 -1.32 (m, 2 H) , 1.36 -1.47 (m, 2 H) , 1.69 -1.87 (m, 3 H) , 2.07 -2.16 (m, 1 H) , 2.22 -2.42 (m, 2 H) , 3.69 (s, 3 H) , 4.56 -4.76 (m, 2 H) , 6.79 (s, 1 H) , 8.31 (d, J 2.74 Hz, 1 H) , 8.45 (d, J 2.74 Hz, 1 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; 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