Month: July 2021

Application of 486424-37-7, These common heterocyclic compound, 486424-37-7, name is 3-Amino-6-bromopyrazine-2-carboxylic acid, 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 containing 1.63 g (7.5 mmol) of 2-amino-5-bromopyrazine carboxylic acid in 25 mL of DMF was added 3.54 g (9.36 mmol) of HATU. The reaction mixture was allowed to stir for 15 minutes before the addition of 1.68 g (9.36 mmol) of 3-amino-4- morpholinopyridine and 2.5 mL (22.5 mmol) of N-methylmorpholine. The reaction was stirred for 16 h then quenched with a 10 mL of a saturated NaHCO, solution and extracted with EtOAc three times. The combined organic extracts were washed with brine and dried over Na2S04. Evaporation of the solvent and column chromatography (Si02; 10% CH3OH /DCM) provided Intermediate A as a yellow solid. 1H NMR (CD3OD) d 9.51 (s, 1H), 8.76 (s, 1H), 8.39 (d, J=5.4Hz, 1H), 7.94 (d, J=8. lHz, 2H), 7.39-7.27 (m, 8H), 5.10 (s, 2H), 3.81 (t, J=7.5Hz, 4H), 2.96 (t, J=7.5Hz, 4H). [M+H]+ = 568.1.

Statistics shows that 3-Amino-6-bromopyrazine-2-carboxylic acid is playing an increasingly important role. we look forward to future research findings about 486424-37-7.

Reference:
Patent; SILVERBACK THERAPEUTICS, INC.; SMITH, Sean Wesley; COBURN, Craig Alan; BAUM, Peter Robert; DUBOSE, Robert Finley; (335 pag.)WO2019/227059; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 98-97-5,Some common heterocyclic compound, 98-97-5, name is Pyrazine-2-carboxylic acid, molecular formula is C5H4N2O2, 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.

Pyrazine-2-carb aldehyde A round bottom flask was charged with pyrazine carboxylic acid (17.7 g, 140 mMol), methanol (200 mL) and conc. sulphuric acid (2 mL) and the mixture was stirred at reflux for 4 hrs then left to stand overnight. The next day the mixture was refluxed for 2 more hours. The solvent was then evaporated in vacuo, the residue was diluted with dichloromethane and neutralised with 20% sodium bicarbonate solution. The dichloromethane phase was dried over MgS04 and evaporated to give the crude product as an off-white solid. Purification by column chromatography (silica gel, dichloromethane) gave pyrazinecarboxylic acid methyl ester 13.5 g as a 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 Pyrazine-2-carboxylic acid, its application will become more common.

Reference:
Patent; F2G LTD; WO2005/92304; (2005); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 914452-71-4, 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. 914452-71-4, name is 2-Bromo-6-methylpyrazine, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 2-bromo-6-methyl-pyrazine (3.0 g, 17.31 mmol) in CCl4 (25 mL) was added NBS (4.60 g, 26.01 mmol) and AIBN (0.248 g, 1.734 mmol) at RT. The mixture was stirred at 55 C. for 48 h. H2O was added followed by extraction with EtOAc (3*100 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified over silica eluting with 5% EtOAc:Hexane to obtain i (1.40 g, 32%). 1H NMR (CDCl3, 400 MHz): delta 8.64 (s, 1H), 8.62 (s, 1H) and 4.50 (s, 2H).

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

Reference:
Patent; Biota Europe Ltd.; Lunniss, Christopher James; Palmer, James T.; Pitt, Gary Robert William; Davies, David; Axford, Lorraine Claire; US2013/252938; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, 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 109838-85-9, Formula: C9H16N2O2

At -78° C. 7.80 ml (19.5 mmol) n-butyllithium (2.5 M in hexane) were added dropwise to 2.90 ml (16.2 mmol) (R)-2-isopropyl-3.6-dimethoxy-2,5-dihydropyrazine in 55 ml THF and the mixture was stirred for 2 h at -50° C. Then at -70° C. 4.25 g (17.8 mmol) (iodomethyl)cycloheptane in 15 ml THF were added dropwise, then the mixture was stirred for 30 min at -78° C., for 3 h at 0° C. and overnight at RT. After the addition of water and methanol it was stirred for 20 min at RT. Ethyl acetate was added and the mixture was extracted with saturated, aqueous saline solution. The organic phase was dried and evaporated to dryness by rotary evaporation. The residue was purified by flash chromatography. The fractions containing the product were combined and concentrated by rotary evaporation. The residue obtained was combined with acetonitrile, water and 1M hydrochloric acid and stirred overnight at RT. The acetonitrile was evaporated off and the aqueous phase was neutralised with potassium hydrogen carbonate. It was extracted with ethyl acetate. The combined organic phases were dried and evaporated to dryness by rotary evaporation.Yield: 1.04 g (32percent of theoretical)ESI-MS: m/z=200 (M+H)+ Rt (HPLC): 0.96 min (method A)The enantiomeric (R)-compound may be obtained analogously to the method of synthesis described above using the corresponding (R)-configured reaction component.

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; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; US2012/196872; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Application In Synthesis of 3-Chloropyrazine-2-carbonitrile

2- cyano-3-(4-oxopiperidino)-pyrazine (Compound 56a)A mixture of 2-cyano-3-chloropyrazine (500 mg, 3.4 mmol), piperidin-4-one hydrochloridre monohydrate (1.33 g, 8.5 mmol) and TEA (1.8 ml, 10.3 mmol) in toluene (20 ml) was reacted at 80C for 8 h. After diluting with H20 and EtOAc, the organic phase was evaporated to dryness in vacuo. The crude was purified by automated flash chromatography (Horizon TM – Biotage) eluting with PE – EtOAc 80:20, affording a yellow solid. Yield: 69%.MS: [M+H]+ = 203.15

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

Reference:
Patent; RECORDATI IRELAND LIMITED; LEONARDI, Amedeo; MOTTA, Gianni; RIVA, Carlo; GUARNERI, Luciano; GRAZIANI, Davide; MARINONI, Fabio; BETTINELLI, Ilaria; WO2011/29633; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 1196152-38-1, name is 2-Bromo-5-(trifluoromethyl)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. Product Details of 1196152-38-1

Example 44k (300 mg, 0.8 mmol), 2-Chloro-5-(trifluoromethyl)pyrimidine (199 mg, 1.09 mmol) and N,N-diisopropylethylamine (287 mul, 1.67 mmol) are dissolved in 4 ml of anhydrous DMSO and heated in a microwave reactor during 30 minutes at 150C. The crude is partitioned between EtOAc and water, the organic layer is dried over anhydrous Na2S04 then concentrated under reduced pressure to obtain 360 mg of the title product. HPLC-MS (Method 10): Rt = 3. MS (ES+): m/z = 505 [M+H]+ . The enantiomers are obtained by HPLC using a chiral stationary phase. Method for separation: HPLC apparatus type: Waters 600 Pump; column: Daicel Chiralpack AD-H, 5.0 muiotaeta, 250 mm x 20 mm; method: eluent hexane/ IPA 70:30; flow rate: 15 mL/min, Temperature: 25 C; UV Detection: 254 nm Example of separation by chiral HPLC: Submitted to separation: 665 mg of Example 1 prepared as described above; Obtained: 157 mg of enantiomer 1 (Exp. 2) and 40 mg of enantiomer 2 (Exp. 3). Example 26 is synthesized as described for example 1 starting from example 44k (70 mg, 0.18 mmol), 2-Bromo-5-(trifluoromethyl)pyrazine (60 mg, 0.26 mmol) instead of 2- Chloro-5-(trifluoromethyl)pyrimidine, N,N-diisopropylethylamine (60 mu, 0.35 mmol) and 1 ml of anhydrous DMSO. The reaction mixture is heated in a microwave reactor during 30 minutes at 150 C. After the work-up, the crude product is purified by preparative HPLC-MS to obtain the title compound (43 mg, 48 % yield). HPLC-MS (Method 10): Rt = 3. MS (ES+): m/z = 505 [M+H]+ .

The synthetic route of 2-Bromo-5-(trifluoromethyl)pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; HOENKE, Christoph; GIOVANNINI, Riccardo; LESSEL, Uta; ROSENBROCK, Holger; SCHMID, Bernhard; WO2015/55698; (2015); 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. 762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, A new synthetic method of this compound is introduced below., Formula: C6H8ClF3N4

General procedure: To the stirred reaction mixture of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo-[4,3-a]pyrazine hydrochloride(11) (300 mg, 1.32 mmol), TEA (0.55 mL, 3.95 mmol)and toluene (10 mL), substituted cyanates 12(a-e)/isocyanates12(f-j) (1.32 mmol) were added at ambient temperature.The reaction mass was agitated at 75-80 C until thecompletion of the reaction that was monitored by TLC. Thereaction mass was allowed to cool at ambient temperatureand it was washed sequentially with 3% aqueous HCl(5.0 mL) and then water (5.0 mL). The organic fraction wasconcentrated under vacuum at 50-55 C to obtain crudeproduct. It was purified by column chromatography using10-50% of EtOAc:hexane mixture as a mobile phase.

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; Mannam, Madhava Rao; Devineni, Subba Rao; Pavuluri, Chandra Mouli; Chamarthi, Naga Raju; Kottapalli, Raja Sekhara P.; Phosphorus, Sulfur and Silicon and the Related Elements; vol. 194; 9; (2019); p. 922 – 932;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 32587-10-3, These common heterocyclic compound, 32587-10-3, name is 3-Aminopyrazine-2-carboxamide, 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.

EXAMPLE 3 Synthesis of 3-Aminopyrazine-2-carbonitrile (Intermediate 2) To a solution of intermediate 1 (3.5 g, 25 mmol) in DMF (40 mL) at RT was added POCl3 (4.5 mL, 49 mmol) slowly. The resulting mixture was heated at 80 C. for 15 min and then cooled to RT. The mixture was poured into ice water and the mixture neutralized with 10% NaOH solution. The resulting solid was filtered and redissolved in 5% HCl. The solution was heated at 70 C. for 30 min and the resulting solid filtered. After thoroughly washed with water, the title compound was obtained as a brown solid (1.7 g, 56%). 1H NMR (500 MHz, DMSO-d6): delta 8.28 (d, J=2.4 Hz, 1H), 7.90 (d, J=2.4 Hz, 1H), 7.32 (br s, 2H). MS (ES+): m/z 121 (M+H)+.

Statistics shows that 3-Aminopyrazine-2-carboxamide is playing an increasingly important role. we look forward to future research findings about 32587-10-3.

Reference:
Patent; TargeGen, Inc.; US2007/259876; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 89123-58-0, These common heterocyclic compound, 89123-58-0, name is 5-Bromopyrazine-2,3-diamine, 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-Bromopyrazine-2,3-diamine (27) was preparedfrom 2-amino-3,5-dibromopyrazine and NH4OH (25%) in sealedtube according to lit.33 1H-NMR delta ppm (CD3OD): 4.90 (s,4H,NH2),7.24 (s,2H,H-5,6). 13C-NMR (CD3OD): 123.3, 129.8, 144.3, 145.9. MS(ESI+) m/z: 189(M + H, 100%), 191(M + H+2, 97%). 27 (0.303 g,1.6 mmol) in EtOH (10 mL) was reduced by hydrogenation using 40psi of H2 and 10% Pd-C (15 mg) for 8 h. The catalyst was filtered ona bed of Celite, the filtrate was concentrated in vacuo. Purplecolored powder 28 were used for the further steps without purification.1H-NMR delta ppm (CD3OD): 4.90 (s,4H,NH2), 7.24 (s,2H, H-5,6). 13C-NMR (CD3OD): 123.7, 145.1. MS (ESI) m/z: 110(M + H,100%). 29 was prepared from 28 (0.11 g) and Na2S2O5 adduct of 4-(morpholin-4-ylcarbonyl) benzaldehyde (0.323 g) as described ingeneral method. Resulting precipitate (0.155 g) was purified withcolumn chromatography using CH2Cl2: MeOH (95 : 5) as eluant,yield 0.056 g, (18%), mp > 300 C. 1H-NMR delta ppm (DMSO-d6+D2O):3.27-3.61 (m,8H), 7.62 (d,2H,J – 8.4 Hz), 8.33 (d,2H,J – 8.4 Hz), 8.40(s,2H,H-5,6). 13C-NMR (DMSO-d6+D2O): 66.0, 127.3, 127.8, 129.9,138.2, 139.0, 154.7, 168.2. MS (ESI) m/z: 310(M + H, 100%). AnalCalcd for C16H15N5O2H2O: C, 58.70; H, 5.23; N, 21.39. Found: C,58.97; H, 5.01; N, 20.91.

Statistics shows that 5-Bromopyrazine-2,3-diamine is playing an increasingly important role. we look forward to future research findings about 89123-58-0.

Reference:
Article; Karaaslan, Cigdem; Doganc, Fatima; Alp, Mehmet; Koc, Asli; Karabay, Arzu Zeynep; Goeker, Hakan; Journal of Molecular Structure; vol. 1205; (2020);,
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. 27825-21-4, name is Methyl 3-chloropyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C6H5ClN2O2

To a solution of the product from step 1 (100 mg, 0.58 mmoi) in toluene (2 mL) was added Pd(PPh3)4 (134 mg, 0.12 mmol) and 2ttributylstannyl)pyridine (213 mg, 0,58 mrnol) at room temperature and the resulting mixture heated to 100 C overnight. After cooling to RI, the mixture was filtered and 5 rnL of aq. KF solution was added to the filtrate. The resulting mixture was stirred for 30 mins and extracted with EtOAc (5 mL x3). The combined organic layerswere washed with brine, dried over Na2504, filtered and concentrated in vacuo, The residue was purified by chromatography (30% EtOAc in petroleum ether) to provide the title compound as a oil. LRMS nih (M-f-H) 216.1 found, 216,1 required.

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 27825-21-4.

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