Tag: M.W=100-200

Reference of 33332-28-4,Some common heterocyclic compound, 33332-28-4, name is 2-Amino-6-chloropyrazine, molecular formula is C4H4ClN3, 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.

2,6-Dichloropyrazine (2.89 g, 19.4 mmol) was stirred in aqueous NH3 (28%, 10 ml.) and heated to 100C in a sealed tube for 18 hours. The reaction mixture was cooled and the resultant precipitate was filtered. Trituration with water and then ether gave 6- chloropyrazin-2-amine as a white solid (2.28 g, 17.6 mmol, 91 % yield). 1H NMR (d6-DMSO, 400 MHz) ? 6.9 (brs, 2H), 7.70 (d, J = 0.4, 1 H), 7.80 (d, J = 0.4, 1 H); LC-MS (ZQ, 6 minutes) Rt = 1.05 minutes; m/z (ESI+) 130 (M+H).6-Chloropyrazin-2-amine (2.50 g, 19.3 mmol) was stirred in CH2CI2 (60 ml.) at 0C.A/-Bromosuccinimide (2.92 g, 16.4 mmol) was added slowly and the reaction mixture was stirred at 0C for 60 minutes. The reaction mixture was filtered through celite and concentrated to give a brown oil. Purification by flash chromatography, eluting with 0-25% EtOAc-hexanes, gave 5-bromo-6-chloropyrazin-2-amine as a yellow solid (1 .69 g, 8.16 mmol, 42% yield). 1H NMR (de-DMSO, 400 MHz) ? 7.1 (brs, 2H), 7.65 (s, 1 H); LC-MS (ZQ, 4 minutes) Rt = 1.46 minutes; m/z (ESI-) 205 (M-H).A mixture of 5-bromo-6-chloropyrazin-2-amine (1 .00 g, 4.8 mmol), copper (I) iodide (914 mg, 4.8 mmol), 18-crown-6 (95 mg, 0.36 mmol) andtetrakis(triphenylphosphine)palladium (0) (83 mg, 0.072 mmol) was suspended in dry DMF (20 ml.) and a stream of nitrogen was passed through for 5 minutes. Potassium cyanide (312 mg, 4.8 mmol) was added and the mixture was stirred at room temperature for 30 minutes, then refluxed at 200C for 3 hours. The mixture was cooled, diluted with EtOAc and absorbed onto silica gel (10 g). DMF was removed by evaporation. The product was purified by flash chromatography, eluting with 1 :1 EtOAc-hexanes, to yield 5- amino-3-chloropyrazine-2-carbonitrile as a yellow solid (607 mg, 3.93 mmol, 82% yield). 1H NMR (d6 DMSO, 400 MHz) ? 7.87 (s, 1 H), 8.1 (brs, 2H); LC-MS (ZQ, 4 minutes) Rt = 1.20 minutes; m/z (ESI-) 153 (M-H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Amino-6-chloropyrazine, its application will become more common.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; COLLINS, Ian; LAINCHBURY, Michael; MATTHEWS, Thomas Peter; READER, John Charles; WO2013/68755; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, 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. Product Details of 109838-85-9

To a 100 mL three neck round bottomed flask under nitrogen atmosphere, (R)-2- isopropyl-3,6-dimethoxy -2,5- dihydropyrazine (4 g, 21.7 mmol) was dissolved in dry THF (28 mL) and cooled to -78 C. To this reaction mixture, 1.6 M solution of n-BuLi in hexanes (16.28 mL, 26 mmol) was added dropwise at -78 C and stirred at same temperature for 15 minutes. After 15 minutes, l-bromo-3- (2-bromoethyl)benzene (5.73 g, 21.7 mmol) in dry THF (13 mL) was added dropwise at -78 C and stirred at -78 C for 1 h followed by stirring at room temperature (rt) for 3 h. The reaction was monitored by TLC using ethyl acctatc hcxancs (0.3:9.7) as a mobile phase. After completion of the reaction, reaction mixture was quenched with saturated ammonium chloride solution (75 mL) and extracted using ethyl acetate (3 x 100 mL). Combined organic layer was dried over sodium sulphate and concentrated to give crude which was purified by flash column purification with 1-3 % ethyl acetate in hexanes to yield 3.3 g of (2S,5R)-2-(3-bromophenethyl)-5- isopropyl-3, 6-dimethoxy-2,5-dihydropyrazine (41.38% yield).

The synthetic route of 109838-85-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PRINCIPIA BIOPHARMA INC.; LOU, Yan; OWENS, Timothy Duncan; BRAMELD, Kenneth Albert; GOLDSTEIN, David Michael; (171 pag.)WO2019/99576; (2019); 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. 136927-64-5, name is 1-Chloropyrrolo[1,2-a]pyrazine, A new synthetic method of this compound is introduced below., Recommanded Product: 136927-64-5

To a mixture of 1 (120 mg, 0.59 mmol) and 2 (90 mg, 0.59 mmol) was added 1.0 ml of Hunig?s base (5.5mmol). The resulting mixture was stirred at 130 C. for 3 h. After the mixture was cooled down to room temperature, 200ml of isopropanol/chloroform (1:2) was added, and the organics were washed with saturated aqueous NaHC03 (2×20 ml)and brine (2×50 ml). The organics were dried over MgSO4 and concentrated under reduced pressure. The residue was purified via flash column chromatography on silica gel (0-10% MeOH in EtOAc) to get the desired product 3 as a brown powder (150 mg, 79%).

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; ChemoCentryx, Inc.; Fan, Junfa; Krasinski, Antoni; Lange, Christopher W.; Lui, Rebecca M.; McMahon, Jeffrey P.; Powers, Jay P.; Zeng, Yibin; Zhang, Penglie; US2014/154179; (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. 59489-71-3, name is 2-Amino-5-bromopyrazine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2-Amino-5-bromopyrazine

Intermediate 6a: 5-(3-(trifluoromethyl phenyl pyrazin-2-amine.; Into a 500-mL sealed tube purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 5-bromopyrazin-2-amine (4 g, 22.99 mmol, 1.00 equiv) in 1,4-dioxane (68 mL) and methanol (23 mL), 3-(trifluoromethyl)phenylboronic acid (4.46 g, 23.48 mmol, 1.02 equiv), a solution of sodium carbonate (4.88 g, 46.04 mmol, 2.00 equiv) in water (23 mL), and Pd(PPh3)4 (532 mg, 0.46 mmol, 0.02 equiv). The resulting solution was stirred overnight at 135C in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1 :5). This resulted in 4.4 g (80%) of 5-(3- (trifluoromethyl)phenyl)pyrazin-2-amine as a yellow solid.

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 59489-71-3.

Reference:
Patent; ARDELYX, INC.; LEWIS, Jason, G.; JACOBS, Jeffrey, W.; REICH, Nicholas; LEADBETTER, Michael, R.; BELL, Noah; CHANG, Han-Ting; CHEN, Tao; NAVRE, Marc; CHARMOT, Dominique; CARRERAS, Christopher; LABONTE, Eric; WO2012/6474; (2012); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 6863-73-6, 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. 6863-73-6, name is 3-Chloropyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows.

Bromoacetaldehyde diethyl acetal (200 ml_, 1.3 mol) and a solution of 48% HBr (48 ml) are heated at reflux for 1.5 hours, then poured onto a suspension of NaHCO3 (10Og) in propan-2-ol (1.6 L). The resulting solid is filtered off and 2-amino-3-chloropyrazine (51.8 g, 0.4 mol) is added to the solution then heated to reflux, during which time a clear solution forms which precipitates over 2 hours. The reaction mixture is cooled and allowed to stand overnight, and the solid may be collected by filtration and washed with propan-2-ol and Et2O. The solid is added to a saturated solution of NaHCO3 (500 ml.) and DCM (1 L). The aqueous layer is separated from the organic solvent and re-extracted with DCM (2 x 250 mL). The organic layers are combined and dried over MgSO4, filtered and evaporated to dryness, to afford a light brown solid. The propan-2-ol and Et2O liquors from washing the filter cake, are evaporated to give a pale brown solid which is washed with a saturated solution of NaHCO3 and extracted with DCM (X 3). The two solids were combined to afford compound 8-chloro-imidazo[l,2-a]pyrazine (59.1 g, 96%).

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

Reference:
Patent; BIOFOCUS DPI LIMITED; WO2009/24585; (2009); 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. 23688-89-3, name is 6-Chloropyrazine-2-carboxylic acid, A new synthetic method of this compound is introduced below., Recommanded Product: 6-Chloropyrazine-2-carboxylic acid

SOCl2 (0.71 mL, 2.84 mmol) and DMF (0.025 mL) were added dropwise to a suspension of 6-chloro-pyrazine -2-carboxylique acid (0.450 g, 2.84 mmol) in toluene (1 mL) and the RM was stirred at 80-90C for 2 h. The solvent was evaporated off under reduced pressure and the residue was dissolved in THF (10 mL) and acetone ( 20 mL), cooled to 0 under argon atmosphere, pyridine ( 0.689 mL, 8.52 mmol), a solution of 4-(trifluoromethoxy)aniline (0.593 mL, 4.42 mmol) in acetone (5 mL) and DMF (1 mL) were added and the RM was stirred at RT overnight. The mixture was treated with aq. 1M HC1 (40 mL) and extracted with EtOAc/TBME (1 :4). The combined extracts were washed with aq. 1M HC1, water, brine and dried over MgSC and the solvent was evaporated off under reduced pressure. The residue was purified by flash chromatography (Silica gel column, 25 g, cyclohexane / EtOAc from 5% to 30% EtOAc) and afforded 6-chloro-N-(4-(trifluoromethoxy)phenyl)pyrazine-2-carboxamide as a yellow oil of which (50 mg, 0.157 mmol), pyrimidin-5-ylboronic acid (39.0 mg, 0.315 mmol), Pd(PPh3)2Cl2 (6.63 mg, 0.0094 mmol), Na2C03 (66.7 mg, 0.630 mmol), DME (668 muGamma), water (191 muGamma) and EtOH (95 mu) was stirred at 80-85C for 1 h. The RM was diluted with THF (2 mL), stirred overnight with Si-Thiol (Silicycle, 124 mg, 0.157 mmol), filtered and the filtrate was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel column, 4 g, DCM / EtOAc + 0.1% NH4OH from 20% to 80% EtOAc+ 0.1% NH4OH) Crystallization from MeOH afforded the title product as white needles. UPLC-MS (Condition 1) tR= 2.68 min, m/z =362.0 [M+H]+, m/z = 360.0 [M-H]”; XH-NMR (400 MHz, DMSO-d6) d ppm 7.45 (d, J=8.6 Hz, 2 H) 8.01 (d, J=9.0 Hz, 2 H) 9.35 (s, 1 H) 9.38 (s, 1 H) 9.69 (s, 1 H) 9.88 (s, 2 H) 10.85 (s, 1 H) .

The synthetic route of 23688-89-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; FURET, Pascal; GROTZFELD, Robert Martin; JONES, Darryl Brynley; MANLEY, Paul; MARZINZIK, Andreas; MOUSSAOUI, Saliha; PELLE, Xavier Francois Andre; SALEM, Bahaa; SCHOEPFER, Joseph; WO2013/171641; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 723286-68-8, 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. 723286-68-8, name is Ethyl 5,6,7,8-Tetrahydro-1,2,4-triazolo[4,3-a]pyrazine-3-carboxylate belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

General procedure: General procedure B A solution of amino nucleophile (3 equiv.), triethylamine (10 equiv.), and Intermediate 1 (1 equiv.) was stirred in dioxane and water (2:1 ratio) at 90 C until complete consumption of starting material was observed by LC/MS. The solution was diluted withiN hydrochloric acid and dichloromethane. The layers were then separated and thelayer was extracted with dichloromethane. The organics were combined, dried over magnesium sulfate, filtered, and the solvent was removed in vacuo. Purification yielded theproduct The title compound was prepared following general procedure B, except ethyl 5,6,7, 8-tetrahydro- [1 ,2,4]triazo lo [4,3 -a]pyrazine-3 -carboxylate (4 equiv.) was the aminereactant, and the reaction was run in THF. The workup was carried out in dichloromethane and brine. The crude material was purified via silica gel chromatography utilizing a 0-10% methanolldichloromethane gradient to deliver the desired compound, Compound 1-115 (42 mg, 37% yield) as a solid.1H-NMR (400 MHz, CDC13) oe 8.47 (d, 1H), 8.35 (d, 1H), 7.40 (s, 1H), 7.21-7.16(m, 1H), 7.01 (t, 1H), 6.95 (t, 1H), 6.84 (t, 1H), 6.65 (d, 1H), 5.98 (s, 2H), 5.35 (s, 2H), 4.59 (t, 2H), 4.48 (q, 2H), 4.30 (t, 2H), 1.44 (t, 3H).

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 5,6,7,8-Tetrahydro-1,2,4-triazolo[4,3-a]pyrazine-3-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NAKAI, Takashi; MOORE, Joel; PERL, Nicholas Robert; IYENGAR, Rajesh R.; MERMERIAN, Ara; IM, G-Yoon Jamie; LEE, Thomas Wai-Ho; HUDSON, Colleen; RENNIE, Glen Robert; JIA, James; RENHOWE, Paul Allen; BARDEN, Timothy Claude; YU, Xiang Y; SHEPPECK, James Edward; IYER, Karthik; JUNG, Joon; WO2014/144100; (2014); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 14508-49-7, These common heterocyclic compound, 14508-49-7, name is 2-Chloropyrazine, 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.

General procedure: A mixture of 2-chloropyrazine (1mmol), 4-ethylphenylboronic acid or 4-methoxy-phenyl boronic acid (1.5mmol), K2CO3 (3mmol), Pd(OAc)2 (0.03mmol), water (2mL) and ethanol (6mL) was stirred at 90C in air for 24h. The reaction mixture was extracted with ethyl acetate, then the combined organic layers were washed with water, dried over MgSO4, filtered, and the solvent was removed on a rotary evaporator. The products were isolated by flash chromatography on silica gel with CH2Cl2 as eluent. The characterization data for 1: Yield: 87%.

Statistics shows that 2-Chloropyrazine is playing an increasingly important role. we look forward to future research findings about 14508-49-7.

Reference:
Short Survey; Xu, Chen; Wang, Zhi-Qiang; Yuan, Xiao-Er; Han, Xin; Xiao, Zhi-Qiang; Fu, Wei-Jun; Ji, Bao-Ming; Hao, Xin-Qi; Song, Mao-Ping; Journal of Organometallic Chemistry; vol. 777; (2015); p. 1 – 5;,
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 274-79-3 as follows. Safety of Imidazo[1,2-a]pyrazine

Step 2 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine Imidazo[1,2-a]pyrazine 4b (500 mg, 4.20 mmol) was dissolved in 5 mL of 2-methoxyethanol, followed by addition of platinum dioxide (100 mg, 0.36 mmol), and the reactor was purged with hydrogen for three times. After stirring for 12 hours, the reaction mixture was filtered. The filtrate was concentrated under reduced pressure to obtain 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine 4c (200 mg, yield 38.7%) as a yellow oil. MS m/z (ESI): 124.1 [M+1]

According to the analysis of related databases, 274-79-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JIANGSU HANSOH PHARMACEUTICAL CO., LTD.; Tang, Peng Cho; Li, Xin; Li, Xiangqin; Chen, Yang; Wang, Bin; Zhu, Zhe; US2013/131068; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 313339-92-3, 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 313339-92-3 as follows.

Example 35 Preparation of 5-((1R,2S)-2-aminocyclohexylamino)-3-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide The title compound was prepared according to the synthetic scheme illustrated below: To the solution of 3,5-dichloropyrazine-2-carbonitrile (2.00 g, 11.5 mmol) in 30 mL NMP were added tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (2.71 g, 12.6 mmol) and DIEA (4.07 mL, 13.8 mmol). The mixture was stirred at RT for 1.5 h. To it was poured 300 mL water. After stirring vigorously for 2 h, the solid was isolated by filtration, washed with water and dried in vacuum oven for overnight to afford tert-butyl (1S,2R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)cyclohexylcarbamate in quantitative yield.

According to the analysis of related databases, 313339-92-3, the application of this compound in the production field has become more and more popular.

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