Month: April 2021

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. 24241-18-7, name is 2-Amino-3,5-dibromopyrazine, A new synthetic method of this compound is introduced below., Formula: C4H3Br2N3

(a)To a 100 mL autoclave was added 2-amino-3,5-dibromopyrazine (10 g, 39.54 mmol, 1 eq) and aqueous ammonia (50 mL, commercially available).The temperature was raised to 130 C under nitrogen atmosphere to carry out the reaction overnight (10 to 12 hours); the temperature was lowered, suction filtration, and the obtained solid was vacuum dried to obtain 5.0 g of compound II.

The synthetic route of 24241-18-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Suzhou Derivative Biological Technology Co., Ltd.; Liu Ke; (7 pag.)CN108707150; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 59489-71-3, A common heterocyclic compound, 59489-71-3, name is 2-Amino-5-bromopyrazine, molecular formula is C4H4BrN3, 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 2; 5-bromopyrazine-2-carbonitrile; i) Tetrakis (triphenyl phosphine) palladium(0) (10 mg) was added to a mixture of 5-bromopyrazin-2-amine (0.575 mmol), potassium cyanide (1.15 mmol), copper (I) iodide (0.575 mmol) and 18-crown-6 (20 mg) in dry DMF (1 mL) in a screw top reaction vessel under nitrogen atmosphere, and the mixture was heated with stirring at 200 C. for 1 h. After cooling, water (5 mL) was added and the product was extracted with chloroform (2¡Á) to give 5-aminopyrazine-2-carbonitrile after purification by chromatography (silica, hexane:ethyl acetate) (0.208 mmol, 36%).

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; AstraZeneca AB; NPS PHARMACEUTICALS, INC.; US2007/37820; (2007); 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. 1458-01-1, name is Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., category: Pyrazines

General procedure: Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate 2 (1 eq.) was combined with K2CO3 (10 eq.), the appropriate (het)aryl boronic acid (1.5 eq.) and Pd(PPh3)4 (5 mol%) in a two-neck round bottom flask. The flask was connected to a condenser and purged with nitrogen. A 4:1 mixture of anhydrous toluene: MeOH (60 mL) was added via syringe and the reaction mixture was heated at reflux for 0.5-18 h. The mixture was allowed to cool to room temperature and filtered through Celite (10 x 3 cm, eluting with 3 x 20 mL EtOAc). The filtrate was evaporated to dryness and the residue purified by silica gel flash column chromatography using EtOAc/pet spirit.

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; Buckley, Benjamin J.; Majed, Hiwa; Aboelela, Ashraf; Minaei, Elahe; Jiang, Longguang; Fildes, Karen; Cheung, Chen-Yi; Johnson, Darren; Bachovchin, Daniel; Cook, Gregory M.; Huang, Mingdong; Ranson, Marie; Kelso, Michael J.; Bioorganic and Medicinal Chemistry Letters; vol. 29; 24; (2019);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 19847-12-2,Some common heterocyclic compound, 19847-12-2, name is Pyrazinecarbonitrile, molecular formula is C5H3N3, 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.

Reference Example 32: 3-Chloropyrazine-2-carbonitrile Pyrazine-2-carbonitrile (26.36 g) is dissolved in toluene (187 ml)/N,N-dimethylformamide (19 ml), and thereto is added dropwise sulfuryl chloride (135 g) under ice-cooling. After completion of addition, the reaction solution is warmed to room temperature gradually and stirred overnight. The toluene layer is separated and the residual red oil is extracted with diethyl ether. The organic layers are combined, cooled with ice, and after pouring thereto ice-water, neutralized by adding saturated aqueous sodium hydrogen carbonate solution. The organic layer is separated, and aqueous layer is extracted with diethyl ether. The organic layers are combined, washed with water, dried over sodium sulfate and evaporated to remove the solvent under reduced pressure. The resulting residue is purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate = 4/1) to give the title compound (16.58 g). 1H-NMR(CDCl3, 300MHz) delta:8.66(1H,d,J=2.4Hz), 8.61(1H,d,J=2.4Hz).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Pyrazinecarbonitrile, its application will become more common.

Reference:
Patent; TANABE SEIYAKU CO., LTD.; EP1582521; (2005); 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. 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., name: 5-Methylpyrazine-2-carboxylic acid

HATU (109 mg, 0.0.29 mmol) was added to a solution of 6-(2-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-3-amine (50.0 mg, 0.18 mmol), 5-methylpyrazine-2-carboxylic acid (37.0 mg, 0.27 mmol), and DIEA (78 mul, 0.44 mmol) in DMAC (7 mL) The mixture was stirred at 60 C for 3 h. H2O (45 mL) was added and the resulting ppt was collected by filtration, rinsed with H2O, and dried under vacuum. The crude residue was purified by MPLC eluting with CH2Cl2/MeOH (0-5%). The product was further purified by recrystallization from CH3CN to give 5-methyl-N-(6-(2-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-3-yl)pyrazine-2-carboxamide (55.0 mg, 77% yield). MS (ESI) calcd for C19H13F3N6O (m/z): 398.11; found: 399 [M+H].

According to the analysis of related databases, 5521-55-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GlaxoSmithKline LLC; CASAUBON, Rebecca, L.; NARAYAN, Radha; OALMANN, Christopher; VU, Chi, B.; (583 pag.)EP2768509; (2017); B1;,
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. 68774-77-6, name is 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine, A new synthetic method of this compound is introduced below., category: Pyrazines

A mixture of (0.070 g, 0.13 mmol), 8-chloro-[l,2,4]triazolo[4,3-a]pyrazine (0.020 g, 0.13 mmol) and sodium carbonate monohydrate (0.016 g, 0.13 mmol) in ethanol (2 mL) and dimethylformamide (2 mL) was heated at 45 C for 4 days. The mixture was brought to RT, concentrated, and the residue was dissolved in ethyl acetate. The organic phase was washed with water, brine, dried over MgSO4, filtered, concentrated, and purified by HPLC to afford (2R,3,S)-3- ([l,2,4]triazolo[4,3-a]pyrazin-8-ylamino)-4-(3,5-difluorophenyl)-l-((R)-2,2- spirocyclobutane-6-neopentyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-4-ylamino)butan-2- ol as a light yellow solid. MS m/z: 577.8 (M+l).

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; AMGEN INC.; WO2009/64418; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 4858-85-9, name is 2,3-Dichloropyrazine, molecular formula is C4H2Cl2N2, 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: C4H2Cl2N2

Step 1: 2-Chloro-3-(2-phenoxyethylamino)pyrazine. A mixture of 2-phenoxyethylamine (2.65 g, 19.3 mmol), 2,3-dichloropyrazine (2.88 g, 19.3 mmol) and K2CO3 (2.67 g, 19.3 mmol) in acetonitrile (8 mL) was stirred in a sealed tube for 12 h at room temperature, and for a further 9.5 h at 80 C. The reaction mixture was diluted with ether, filtered, and concentrated. The residue was purified by chromatography on silica gel using n-hexane/EtOAc (7:3) as eluent to give 2.36 g (49%) of the title compound as a yellowish oil that solidified on standing: mp 51-53 C.; HRMS m/z calcd for C12H12ClN30 (M)+249.0669, found 249.0659. Anal. (Cl2H12ClN30) C, H, N.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4858-85-9, its application will become more common.

Reference:
Patent; Biovitrum AB; US6465467; (2002); B1;,
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. 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, A new synthetic method of this compound is introduced below., category: Pyrazines

General procedure: 2-Bromo-5H-pyrrolo[3,2-b]pyrazine(4; 0.471 g,2.39 mmol), 4-pyridylboronic acid (0.58 g, 4.72 mmol), dichloro 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloromethane adduct (0.097 g, 0.12 mmol), acetonitrile(3 mL) and 1M sodium carbonate (3 mL) were placed in a 10 mL CEM microwavevial. The vial was capped and irradiated in a CEM microwave reactor for 30minutes at 150 C.Water (3 mL) and ethyl acetate (9 mL) were added the layers were partitioned. Theaqueous layer was extracted with ethyl acetate (2 x 10 mL). The combined organicextracts were washed with saturated sodium chloride (5 mL), dried over MgSO4and concentrated under reduced pressure. The residue was purified by preparativereverse phase HPLC to give 2-(pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazine(14; 0.28 g,60%) as an off white solid: 1H NMR (400 MHz, DMSO-d6) delta 12.24 (s, 1H), 9.00(s, 1H), 8.69 (dd, J = 4.5, 1.6 Hz, 2H), 8.12 (dd, J = 4.5, 1.6Hz, 2H), 7.98 (d, J = 3.6 Hz, 1H), 6.74 (d, J = 3.6 Hz, 1H); ESMSm/z 197.1 (M+1).

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; Burdick, Daniel J.; Wang, Shumei; Heise, Christopher; Pan, Borlan; Drummond, Jake; Yin, Jianping; Goeser, Lauren; Magnuson, Steven; Blaney, Jeff; Moffat, John; Wang, Weiru; Chen, Huifen; Bioorganic and Medicinal Chemistry Letters; vol. 25; 21; (2015); p. 4728 – 4732;,
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. 68774-77-6, name is 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. category: Pyrazines

The following examples in Table I were prepared by Methods A (Scheme 7), B (Scheme 8) or C (Scheme 9) and/or steps analogous to those described in Examples 6, 9, 11 and 21-23 above.Scheme 7 illustrates how one may construct the R1 to amine-backbone bond, where R1, as shown, is an aromatic moiety. Intermediate 8′ can be heated in a microwave oven with a desirably substituted chloro-substituted aromatic compound 18 in the presence of a suitable base, such as dnsopropylethylamine (DIEA) in a suitable solvent, such as isopropyl alcohol (IPA) to afford the desired product compound 19 of Formula I or II.

The synthetic route of 68774-77-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMGEN INC.; WO2009/64418; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 344940-70-1, 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. 344940-70-1 name is 5-Bromo-3-phenylpyrazin-2-amine, 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.

Into a flask, purged with an inert atmosphere of nitrogen, was placed 5-bromo-3-phenylpyrazin-2-amine (300 mg, 1.20 mmol) in EtOH (5.22 mL). 2-Bromo-l,l-diethoxyethane (372 mu, 2.40 mmol) and HBr in water (950 mu, 8.40 mmol) were added. The mixture was warmed at 85C. After 2.5 h, the reaction was cooled to ambient temperature and diluted with EtOAc. The mixture was further cooled to 0C and slowly quenched with saturated aqueous NaHC03 until the pH was adjusted to 9. The resulting solution was extracted with EtOAc (3X). The organic layers were combined and dried over anhydrous sodium sulfate. The solid was filtered and the filtrate was concentrated in vacuo to dryness. The residue was purified by silica gel chromatography with EtOAc:hexanes (0-70%) to afford the title compound.

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

Reference:
Patent; MERCK SHARP & DOHME CORP.; CAMPBELL, Brian, T.; DONG, Guizhen; GARFUNKLE, Joie; KIM, Alexander; ORNOSKI, Olga; PARKER, Dann, L., Jr.; RAGHAVAN, Subharekha; XU, Libo; YANG, Zhiqiang; (191 pag.)WO2015/187470; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem