Pyrazines

These common heterocyclic compound, 330786-09-9, name is Methyl 3,5-dichloropyrazine-2-carboxylate, 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. Safety of Methyl 3,5-dichloropyrazine-2-carboxylate

Step 1: [0443] Dichloropyrazine S1.1 (synthesized as described in Yamada, K.; Mastuki, K.; Omori, K.; Kikkawa, K. US Patent Application 2004/0142930A1) (0.46 g, 2.7 mmol) was diluted with 10 mL of acetonitrile. To this was then added DIPEA (0.52 mL, 3.0 mmol) and cyclopropylamine (0.19 mL, 2.7 mmol) and the reactions stirred at rt overnight. The following day the reaction was concentrated by rotary evaporation and the resulting syrup diluted with water and stirred until a filterable precipitate formed. The solid was isolated by filtration and washed with water affording the desired product as a bright yellow solid containing regioisomers S1.2 and S1.3.

The synthetic route of Methyl 3,5-dichloropyrazine-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Portola Pharmaceuticals, Inc.; Song, Yonghong; Xu, Qing; Jia, Zhaozhong J.; Kane, Brian; Bauer, Shawn M.; Pandey, Anjali; US2013/131040; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 957344-74-0, A common heterocyclic compound, 957344-74-0, name is 5,8-Dibromoimidazo[1,2-a]pyrazine, molecular formula is C6H3Br2N3, 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.

Step 1 4-(5-Bromoiotamiotadazo[l,2-a]pyraziotan-8-ylamiotano) benzoic acid methyl ester[00266] A mixture of 5,8-dibromoimidazo[l,2-a]pyrazme (2g, 7 3mmol), 4-amino benzoic acid methyl ester (0 93g, 6 2mmol), NaO’Bu (0 98g, 10 2mmol), Pd2(dba)3 (133mg, 0 14mmol), Xantphos (168mg, 0 29mmol) and toluene is degassed with nitrogen, then heated at 850C for 18 hours The toluene is removed in vacuo, then MeOH is added to the crude residue The solid is collected by filtration and dried in the vacuum oven The solid is identified as the desired title ester The filtrate is chromatographed with petrol EtOAc (70 30 followed by 50 50) and the fractions containing the desired product, combined, evaporated and triturated with MeOH The resultant solid is collected by filtration and is also identified as the desired ester

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; GALAPAGOS N.V.; WO2007/131991; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 5049-61-6, A common heterocyclic compound, 5049-61-6, name is Pyrazin-2-amine, molecular formula is C4H5N3, 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.

5-bromopvrazin-2-amine (M); To a solution of 2-aminopyrazine (1.00 g, 10.0 mmol) in chloroform (50 mL) and pyridine (0.8 mL, 10.0 mmol), solid pyridineNo.HBr3 (3.37 g, 10.0 mmol) was added in portions over 10 min. The reaction mixture was stirred at room temperature for 2 h. Saturated NaHCOs aqueous solution (25 mL) was added to this reaction mixture carefully (pH 7 to 8) and stirred for 10 min. Organic layer was separated, washed with water (15 mL x 3) (filtered if necessary), dried with Na2S04, filtered, and evaporated to dryness. The residue was purified using column chromatography (silica gel, 1:1:8 hexane/CH2CI2/EtOAc). The fractions containing product were evaporated to dryness under vacuum to yield compound M as a pale yellow solid (601 mg, 3.45 mmol, 35%). ¹H NMR (DMSO-d6, 300 MHz) No. 6.63 (bs, 2H), 7.67 (d, 1H, J, 1.4), 8.02 (d, 1 H, J, 1.4).

The synthetic route of 5049-61-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUGEN, INC.; WO2005/113548; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 13134-38-8, 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. 13134-38-8, name is 3,6-Dimethylpyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows.

To the solution of thus obtained 2-amino-3,6-dimethylpyrazine (4.0 g, 32.5 mmol) in drydichloromethane (150 mL), 6.89 g (29.5 mmol) of O-(diphenylphosphinyl)hydroxylaminewere added at room temperature. The whole was stirred at room temperature for 20 hours. The mixture was concentrated to the constant mass and after addition of isopropanol (50 mL)- toluene (10 mL) mixture concentrated again to remove traces of water. Dry residue was triturated with ethyl ether. Obtained solid was filtered-off and dried under reduced pressure.6.91 g of the title product as a brown solid were obtained (yield 66%). MS-ESI: (mlz) calculated for C6H10N4 [M+H]: 139.09, found 139.1 (pyrazinium cation); calculated for C12H11O2P [M-H]: 217.04, found 217.1 (diphenylphosphinate anion).

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

Reference:
Patent; CELON PHARMA S.A.; MOSZCZYNSKI-PETKOWSKI, Rafal; BOJARSKI, Lukasz; WIECZOREK, Maciej; MAJER, Jakub; JANOWSKA, Sylwia; MATLOKA, Mikolaj; BORKOWSKA, Malgorzata; STEFANIAK, Filip; LAMPARSKA-PRZYBYSZ, Monika; DUBIEL, Krzysztof; WO2015/177688; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 51171-02-9, 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. 51171-02-9 name is Methyl 3-Bromo-2-pyrazinecarboxylate, 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.

A solution of 3-bromopyrazine-2-carboxylic acid methyl ester (0.10 g, 0.45 mmol), 2- tritylsulfanylethylamine (0.29 g, 0.90 mmol) and triethylamine (0.06 mL, 0.44 mmol) in acetonitrile (5 mL) was heated to reflux for 18 h under argon. The mixture was concentrated under reduced pressure and purified by column chromatography (3:1 Hex:EtOAc), yielding 0.058 g (28%) of the desired product.

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

Reference:
Patent; BAYER PHARMACEUTICALS CORPORATION; WO2006/121904; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 36070-83-4, 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. 36070-83-4, name is Ethyl 5-bromopyrazine-2-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a mixture of copper powder (286 mg, 4.50 mmol) and DMF (3.5 mL) was added TFA (11 mu, 0.15 mmol), and the resulting mixture was stirred at room temperature for 30 min. To the mixture were added ethyl 5-bromopyrazine-2-carboxylate (VII, 347 mg, 1.50 mmol) and ethyl bromodifluoroacetate (289 mu, 2.25 mmol), and the mixture was stirred at 50 C for 2 h. To the reaction mixture were added a saturated aqueous sodium bicarbonate solution (10 mL) and ethyl acetate (15 mL), and the organic layer was separated. The organic layers was washed twice with an aqueous sodium chloride solution (5%, 20 mL each). After the organic layer was dried over sodium sulfate, concentration at 40 C under reduced pressure and purification of the residue by silica gel chromatography (ethyl acetate and ft-hexane) afforded the title compound (VIII, 30.9 mg, 8% yield and IX, 34.9 mg, 9% yield). [0052] The data of NMR for the title compound (IX) is as follows. [5-(ethoxycarbonyl)pyrazin-2-yl](difluoro)acetic acid (IX) NMR (400 MHz, CDC13) delta: 1.49 (t, J- 6.8 Hz, 3H), 4.55 (q, J = 6.8 Hz, 2H), 9.40 (s, 1H), 9.76 (s, 1H).

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, Ethyl 5-bromopyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; EISAI R&D MANAGEMENT CO., LTD.; YOSHIZAWA, Kazuhiro; OMORI, Masayuki; WATANABE, Yuzo; NAGAI, Mitsuo; TAKAHASHI, Masabumi; FANG, Frank; WO2013/162065; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 5049-61-6, name is Pyrazin-2-amine, 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 5049-61-6, Product Details of 5049-61-6

Step 1 : 2-Amino-5-bromopyrazine: To a 0C cooled and stirred solution of 2-aminopyrazine (10 g, 105 mmol, 1.0 eq) in DCM (1000 mL) was added N-bromosuccinimide (16.8 g, 94.6 mmol, 0.9 eq) portion wise and the resulting solution was stirred at the same temperature for 30 min. The reaction mixture was filtered while keeping the filtrate at 0C and cold water (500 mL) was added to the filtrate. The layers were separated and the organic layer was washed with brine (200 mL), dried (Na2S04) and filtered. The filtrate was concentrated under vacuum. The crude product was purified by re-crystallization using DCM and hexane to afford 12 g of the desired product as a pale yellow solid. 1HNMR (400 MHz, CDC13) delta 8.06 (s, 1H), 7.75 (s, 1H), 4.72 (brs, 2H, D20 exchangeable); ESI-MS (m/z) 174, 176 [(MH)+ Br79′”].

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, Pyrazin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; LUPIN LIMITED; IRLAPATI, Nageswara, Rao; DESHMUKH, Gokul, Keruji; KARCHE, Vijay, Pandurang; JACHAK, Santosh, Madhukar; SINHA, Neelima; PALLE, Venkata, P.; KAMBOJ, Rajender, Kumar; WO2012/56478; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, 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. Safety of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride

Example-8: Preparation of 7-[(3R)-3-amino-l-oxo-4-(2,4,5-trifluorophenyl) butyl] – 5,6,7,8-tetrahydro-3-(trifluoromethyl)-l,2,4-triazoIo [4.3-a] pyrazine compound of formula- 1.; To 24 ml of dimethylformamide added 4 gms of (R)-3-(tert-butoxycarbonylamino)-4- (2,4,5-trifluorophenyl)butanoic acid and cooled the reaction mixture to 0-5C. 3.3 gms of NjN’-dicyclohexylcarbodiimide (DCC) was dissolved in 10 ml of dimethylformamide and make upto 20 ml. Added 7 ml of above prepared NjN’-dicyclohexylcarbodiimide (DCC) solution to the above 0-5 C cooled reaction mixture. Added 3.15 gms of 3-(trifluoromethyl)-5,6,7,8-tetra hydro-[l,2,4]triazolo[4,3-a]pyrazine hydrochloride and 3.3 ml of triethylamine to the reaction mixture and stirred for 15 minutes. Added 0.9 gms of dimethylaminopyridine (DMAP) and stirred the reaction mixture for 3 hrs at 0-50C. Added 6.5 ml of N,N’-dicyclohexylcarbodiimide solution and stirred for 3 hrs. Again added 6.5 ml of N,N’-dicyclohexylcarbodiimide solution and stirred for 3 hrs at 0-50C. Raised the temperature to 25C and stirred the reaction mixture for 12 hrs at same temperature. The unwanted precipitated solids were separated by filtration and to the filtrate added water and ethyl acetate. Separated the both aqueous and organic layers. Washed the organic layer with 5% hydrochloric acid solution followed by washed with 5% sodium bicarbonate solution. Distilled off the solvent completely under reduced pressure. Added 30 ml of isopropyl alcohol to the obtained compound and stirred for 45 minutes at 25-300C temperature. Filtered the precipitated solid and dried the material. To the obtained compound added 10 ml of isopropyl alcohol and 3.8 ml of cone, hydrochloric acid. Stirred the reaction mixture for 3 hrs at 500C. Cooled the reaction mixture to 25C and added water. Extracted the compound from reaction mixture with methylene chloride. Distilled off the solvent completely to get the title compound. Yield: 2.5 gms.

The synthetic route of 762240-92-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MSN LABORATORIES LIMITED; SATYANARAYANA REDDY, Manne; ESWARAIAH, Sajja; SATYANARAYANA, Revu; KONDAL REDDY, Bairy; SRINIVAS, Aluru; WO2010/122578; (2010); A2;,
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. 767340-03-4, name is (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine, A new synthetic method of this compound is introduced below., SDS of cas: 767340-03-4

Step C: Preparation of (2R)-4-OXO-4-F3- (TRIFLUOROMETHYL)-5, 6- DIHYDROF L, 2. 41TRIAZOLOR4, 3-ALPVRAZIN-7 (8H)-YLL-1-(24*5- TRIFLUOROPHENYL) butan-2-amine (2-5) Into a 500 ml flask were charged chloro (1, 5-cyclooctadiene) rhodium (I) dimer {[Rh (cod) CI] 2} (292 mg, 0.59 mmol) and (R, S) t-butyl Josiphos (708 mg, 1.31 mmol) under a nitrogen atmosphere. Degassed MEOH was then added (200 ML) and the mixture was stirred at room temperature for 1 h. Into a 4 L HYDROGENATOR was charged the enamine amide 2-4 (118 g, 0.29 mol) along with MEOH (1 L). The slurry was degassed. The catalyst solution was then transferred to the hydrogenator under nitrogen. After degassing three times, the enamine amide was hydrogenated under 200 psi hydrogen gas at 50 C for 13 h. Assay yield was determined by HPLC to be 93% and optical purity to be 94% ee. The optical purity was further enhanced in the following manner. The methanol solution from the hydrogenation reaction (18 g in 180 mL MEOH) was concentrated and switched to methyl t-butyl ether (MTBE) (45 mL). Into this solution was added aqueous H3PO4 solution (0.5 M, 95 mL). After separation of the layers, 3N NAOH (35 ML) was added to the water layer, which was then extracted with MTBE (180 mL + 100 mL). The MTBE solution was concentrated and solvent switched to hot toluene (180 mL, about 75 C). The hot toluene solution was then allowed to cool to 0 C slowly (5-10 h). The crystals were isolated by filtration (13 g, yield 72%, 98-99% ee); m. p. 114.1-115. 7 C. 1H NMR (300 MHZ, CD3CN) : 5 7.26 (m), 7.08 (m), 4.90 (s), 4.89 (s), 4.14 (m), 3.95 (m), 3.40 (m), 2. 68 (m), 2.49 (m), 1.40 (bs). Compound 2-5 exists as amide bond rotamers. Unless indicated, the major and minor rotamers are grouped together since the carbon-13 signals are not well resolved: 13C NMR (CD3CN) : 8 171.8, 157.4 (ddd, JCF = 242.4, 9.2, 2.5 HZ), 152.2 (major), 151.8 (minor), 149.3 (DDD ; JCF = 246.7, 14.2, 12.9 Hz), 147.4 (ddd, JCF = 241.2, 12.3, 3.7 Hz), 144.2 (q, JcF = 38. 8 Hz), 124.6 (ddd, JCF = 18. 5,5. 9,4. 0 Hz), 120.4 (dd, JCF = 19.1, 6.2 Hz), 119.8 (q, JCF = 268. 9 Hz), 106.2 (dd, JCF = 29.5, 20.9 Hz), 50.1, 44.8, 44.3 (minor), 43.2 (minor), 42.4, 41.6 (minor), 41.4, 39.6, 38. 5 (minor), 36.9. The following high-performance liquid chromatographic (HPLC) conditions were used to determine percent conversion to product: Column: Waters Symmetry C18, 250 mm x 4.6 mm Eluent: Solvent A: 0.1 vol% HC104/H20 Solvent B : acetonitrile Gradient: 0 min 75% A: 25% B 10 min 25% A: 75% B 12. 5 MIN 25% A: 75% B 15 MIN 75% A: 25% B Flow rate: 1 ML/MIN Injection Vol.: 10 uL UV detection: 210 nm Column temp.: 40 C Retention times: compound 2-4: 9.1 min compound 2-5 : 5.4 min tBu Josiphos: 8.7 min The following high-performance liquid chromatographic (HPLC) conditions were used to determine optical purity: Column: Chirapak, AD-H, 250 mm x 4.6 mm Eluent: Solvent A: 0.2 vol. % diethylamine in heptane Solvent B: 0.1 vol% diethylamine in ethanol Isochratic Run Time: 18 min Flow RATE : 0. 7 mL/min Injection Vol.: 7 uL W detection: 268 nm Column temp.: 35 C Retention times: (-amine 2-5: 13.8 min (-amine : 11.2 min EXAMPLE 2 Methyl (3S)-3-AMINO-3-(6-METHOXYPERIDIN-3-YL) PROPANOATE (3-2) Into a 7 mL vial were charged chloro (1, 5-CYCLOOCTADIENE) rhodium (I) dimer { [Rh (cod) CI] 2} (14.2 mg, 0.029 mmol) and (R, S)-t-Bu Josiphos (31.3 mg, 0.058 mmol) under a nitrogen atmosphere. Degassed methanol (1 mL) was then added and the catalytic complex was stirred for 45 min at room temperature. In a separate 2-mL vial, the enamine ester 3-1 (0.1 g, 0.5 mmol) was dissolved in 0.9 mL distilled 2,2, 2-trifluoroethanol. To the same vial 0.1 RNL of the prepared catalyst solution was added resulting in 1 mol% catalyst loading and a 2,2, 2- trifluoroethanol/methanol mixture of 90/10. The hydrogenation vial was then sealed and transferred into the hydrogenation bomb under nitrogen. After degassing three times with hydrogen, the enamine ester was hydrogenated under 90-psig-hydrogen gas at 50 C for 13.5 h. Assay yield was determined by HPLC to be 88% and optical purity to be 89% ee. 1H-NMR (400 MHz, CDCl3) : 8 1.81 (bs, 2H), 2.64 (m, 2H), 3.68 (s, 3H), 3.91 (s, 3H), 4.4 (dd, 1H), 6.72 (d, 1H), 7.62 (dd, 1H), and 8. 11 (s, 1H) ppm.

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 & CO. INC.; WO2004/85378; (2004); 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. 33332-28-4, name is 2-Amino-6-chloropyrazine, This compound has unique chemical properties. The synthetic route is as follows., Safety of 2-Amino-6-chloropyrazine

To a mixture of compound 9 (312.0 g, 2A mol) and K2C03 (664.0 g, 4.8 mol) in MeCH(1.0 L) was dropwise added lCl (704.0 g, 4.3 mol in 1.0 L of DCM) over 2 hours0C. Then the reaction mixture was stirred at room temperature overnight. Thereaction was quenched with Na2SO3 aqueous solution (2M, 1 .5 L). The mixture was extracted with DCM (1.0 L x 3). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purifiedcolumn chromatography on silica gel (PEIEA = 10/1 to 4/1) to afford compound(460 g, 75% yield) as a solid.1HNMR (400 MHz, DMSQd6): 7.68 (s, 1H), 7.07 (s 2H). MS Calcd.: 255 MS Found: 256 ([M+Hfl.

According to the analysis of related databases, 33332-28-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; H. LUNDBECK A/S; SVENSTRUP, Niels; WEN, Kate; WANG, Yazhou; (78 pag.)WO2017/5786; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem