Tag: M.W=100-200

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. 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

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

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

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

Application of 6863-74-7, These common heterocyclic compound, 6863-74-7, name is 6-Chloropyrazine-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.

Reference Example 109 2-Cyano-6-[2-(dimethylamino)ethylthio]pyrazine 2-Dimethylaminoethanethiol hydrochloride salt (1.46 g, 10.0 mmol) and sodium hydride (60 % in oil, 0.88 g, 22.0 mmol) were added to THF (50 ml), and 2-chloro-6-cyanopyrazine (1.40 g, 10.0 mmol) was added thereto.. The mixture was stirred at room temperature for 18 hrs.. The reaction mixture was combined with ethyl acetate and water.. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate.. The solvent was evaporated, and the residue was recrystallized from n-hexane-ethyl acetate to give the titled compound (1.00 g, 48 %) as pale yellow crystals.1H-NMR (CDCl3) delta: 2.32 (6H, s), 2.62-2.67 (2H, m), 3.31-3.38 (2H, m), 8.48 (1H, s), 8.58 (1H, s). IR(KBr): 2233, 1576, 1549, 1456, 1143, 794 cm-1.

The synthetic route of 6863-74-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Chemical Industries, Ltd.; EP1424336; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 41110-28-5, name is 3-Methylpyrazine-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 41110-28-5, Product Details of 41110-28-5

In a 2-L flask, 3-methylpyrazine-2-carboxylic acid (Matrix, 19.95 g, 144 mmol) was suspended in MeOH (500 mL). The suspension was cooled in an ice-water bath, and concentrated sulfuric acid (Fluka, 27.3 mL, 506 mmol) was added over a time period of 5 min. The reaction mixture was heated to 80 C for 5 h. The reaction mixture was concentrated under reduced pressure and the residue was taken up in DCM (750 mL). The excess acid was neutralized carefully with of aqueous NaOH (5 M, 200 mL). The aqueous layer was separated and extracted with DCM (250 mL). The combined organic layers were combined, dried over MgSO4 and concentrated to afford 16.15 g of methyl 3-methylpyrazine-2-carboxylate (265A, 106 mmol, 73%). MS m/z=153 [M+H]+.

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; AMGEN INC.; ALLEN, Jennifer R.; AMEGADZIE, Albert; BOURBEAU, Matthew P.; BROWN, James A.; CHEN, Jian J.; CHENG, Yuan; FROHN, Michael J.; GUZMAN-PEREZ, Angel; HARRINGTON, Paul E.; LIU, Longbin; LIU, Qingyian; LOW, Jonathan D.; MA, Vu Van; MANNING, James; MINATTI, Ana Elena; NGUYEN, Thomas T.; NISHMURA, Nobuko; NORMAN, Mark H.; PETTUS, Liping H.; PICKRELL, Alexander J.; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert M.; SIEGMUND, Aaron C.; STEC, Markian M.; WHITE, Ryan; XUE, Qiufen; (759 pag.)WO2016/22724; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 33332-25-1, name is Methyl 5-chloropyrazine-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 33332-25-1, Product Details of 33332-25-1

Example 2[6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin- 1-yl)-pyrazin-2-yl] -((R)-2-methyl- pyrrolidin- 1-yl)-methanonea) 5- (3 ,3-Difluoro-azetidin- 1 -yl)-pyrazine-2-carboxylic acid methyl ester 5-Chloro-pyrazine-2-carboxylic acid methyl ester (CAN 33332-25-1; 15 g, 86.92 mmol) was dissolved in dioxane (100 mL). To this solution was added 3,3-difluoroazetidine hydrochloride (CAN 288315-03-7; 13.51 g, 104.31 mmol), and triethyl amine (31.3 mL,226 mmol). The mixture was stirred 22 hours at 45C and afterwards cooled to room temperature. Brine (100 mL) was added and the mixture was extracted with ethyl acetate. The organic phases were washed successively with sodium bicarbonate solution (10%, 300 mL) and brine (200 mL); dried with Na2SO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 200g, 30% to 50% ethyl acetatein hexane) to give the desired product (15 g, 75.3%) as white solid; LC-MS (UV peak area, ESI) 98.6%, 230.4 [MH?i.

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

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; DHURWASULU, Baledi; GRETHER, Uwe; NETTEKOVEN, Matthias; ROEVER, Stephan; ROGERS-EVANS, Mark; SCHULZ-GASCH, Tanja; WO2014/86807; (2014); A1;,
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 33332-28-4 as follows. category: Pyrazines

p. N-(6-Chloro-2-pyrazinyl)-4-hydroxy-2-methyl-2H-naphtho[2, 1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide, m.p. 209¡ã-210¡ã C (from ethanol), from 2-methyl-4-(1-pyrrolidyl)-2H-naphtho[2,1 -e]-1,2-thiazine-3-carboxylic acid chloride-1,1-dioxide and 2-amino-6-chloro-pyrazine.

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; Boehringer Ingelheim GmbH; US3992535; (1976); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 36070-80-1, 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. 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of lenalidomide (0.2g, 0.77 mmol) in DMF (4 mL) was added 5-chloropyrazine-2-carboxylic acid (0.15g, 0.95 mmol), HATU, (0.29g, 0.77 mmol), and DIPEA (0.27mL, 1.54 mmol). The reaction was stirred at room temperature for 1 hr before it was quenched with saturated NH4C1 (5 mL). The mixture was extracted with EtOAc (10 mLx3), and the combined organic phase was dried over Na2S04 and concentrated. Column chromatography gave 5-chloro-N- (2-(2,6-dioxopiperidin-3-yl)-l-oxoisoindolin-4-yl)pyrazine-2-carboxamide (0.1 g, 33%).

The chemical industry reduces the impact on the environment during synthesis 5-Chloropyrazine-2-carboxylic acid. I believe this compound will play a more active role in future production and life.

Reference:
Patent; SYNTA PHARMACEUTICALS CORP.; CHIMMANAMADA, Dinesh, U.; YING, Weiwen; ZHANG, Junyi; KOWALCZYK-PRZEWLOKA, Teresa; JIANG, Jun; OSMAN, Sami; LU, Genliang; VUTUKURI, Dharma; LOCH, James; CHEN, Shoujun; WO2015/38649; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem