Tag: M.W=100-200

Reference of 14508-49-7, A common heterocyclic compound, 14508-49-7, name is 2-Chloropyrazine, molecular formula is C4H3ClN2, 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 10 mL round-bottom flask was charged with the prescribedamount of catalyst Pd/Cu, aryl chlorides (0.5 mmol), phenylboronicacids containing hydroxymethyl (0.75 mmol), Cs2CO3 (1.0 mmol)and dioxane (5 mL) in air. The reaction mixture was then placedin an oil bath and heated at 110 C for 24 h. After removal of thesolvent, the resulting residue was purified by flash chromatographyon silica gel using CH2Cl2 as eluent. The products 4a-k, and4m are known compounds [6,9] except for 4l and 4n.

The synthetic route of 14508-49-7 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Xu, Chen; Li, Hong-Mei; Wang, Zhi-Qiang; Fu, Wei-Jun; Inorganica Chimica Acta; PA; (2014); p. 11 – 15;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 16298-03-6, These common heterocyclic compound, 16298-03-6, name is Methyl 2-aminopyrazine-3-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.

Methyl 3-aminopyrazine-2-carboxylate (100 g, 653.0 mmol) and N- bromosuccinimide (1 16.2 g, 653.0 mmol) were stirred in MeCN (1.198 L) at ambient temperature for 15 hours. The resultant precipitate was isolated by filtration and washed with MeCN (10 mL) and diethyl ether (100 mL) to give the sub-title product as pale yellow flakes (123.73g, 82percent Yield). 1H NMR (400.0 MHz, CDCl3) delta 4.00 (s, 3H), 6.47 (br s, 2H), 7.28 (s, 1H) and 8.31 (s, 1H) ppm; (ES+) 232.0.

Statistics shows that Methyl 2-aminopyrazine-3-carboxylate is playing an increasingly important role. we look forward to future research findings about 16298-03-6.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-Damien; DURRANT, Steven, John; YOUNG, Stephen, Clinton; STORCK, Pierre-Henri; VIRANI, Aniza, Nizarali; REAPER, Philip, Michael; PINDER, Joanne; WO2011/143423; (2011); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 98-97-5, 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. 98-97-5, name is Pyrazine-2-carboxylic acid belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Example 1 A. 4-Azido-1-thiophen-2-yl-butan-1-one A mixture of 4-chloro-2′-butyrothienone (3.0 g, 15.9 mmol) and sodium azide (2.07 g, 31.8 mmol) in DMF (50 mL) was stirred at 70 C. for 1.5 h. The reaction mixture was then partitioned between ethyl acetate (200 mL) and water (200 mL). The organic layer was washed with water (100 mL), saturated aqueous sodium bicarbonate (100 mL) and brine (100 mL) and dried over sodium sulfate. Removal of the solvent in vacuo provided the title compound (2.58 g, 83% yield). MS m/e 218; HPLC retention time 0.85 min (Method B). B. 2-(2-Azido-ethyl)-1-pyrazin-2-yl-3-thiophen-2-yl-propane-1,3-dione A suspension of pyrazine 2-carboxylic acid (2.52 g, 20.3 mmol) in dichloromethane (30 mL) at 0 C. was treated with oxalyl chloride (1.95 mL, 22.3 mmol) followed by the addition of catalytic DMF (1 drop). The reaction mixture was allowed to warm to room temperature overnight, then concentrated in vacuo to give pyrazine 2-carbonyl chloride as a violet-colored solid. In a separate reaction flask, LHMDS (1.0 M in THF, 11.28 mL) was added dropwise to a solution of the ketone 1A (1.10 g, 5.64 mmol) in THF (10 mL) at -78 C. The reaction mixture was maintained at that temperature for 20 min. The pyrazine 2-carbonyl chloride (1.0 g, 5.64 mmol)was then rapidly introduced as a solid to the reaction mixture to give a dark brown solution which was maintained at -78 C. for another 20 min. The reaction mixture was then partitioned between ethyl acetate and saturated aqueous ammonium chloride. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate, then concentrated to give the crude oil. Purification by flash column chromatography (silica, 30% ethyl acetate in hexanes) provided the title compound as a yellow oil (939 mg, 55% yield). MS m/e 324; HPLC retention time 2.78 min (Method A). 1H NMR (400 MHz, CDCl3): delta 2.36 (m, 1 H), 2.58 (m, 1 H), 3.60 (dd, 2 H), 5.82 (dd, 1 H), 7.28 (dd, 1 H), 7.82 (d, 1 H), 8.07 (d, 1 H), 8.67 (s, 1 H), 8.88 (s, 1 H), 9.37 (s, 1 H). C. 2-[4-(2-Azido-ethyl)-5-thiophen-2-yl-2H-pyrazol-3-yl]-pyrazine A solution of the dione 1B (213 mg, 0.71 mmol), hydrazine monohydrate (0.17 mL, 3.54 mmol) and concentrated aqueous HCl (1 drop) in methanol (4 mL) was heated at 70 C. for 1 h. The reaction mixture was then concentrated to give a yellow sticky solid which was purified by flash column chromatography (silica, 1:1 ethyl acetate:hexanes) to give the title compound (142 mg, 67% yield) as a colorless oil. MS m/e 298; HPLC retention time 3.40 min (Method A). 1H NMR (400 MHz, CDCl3): delta 3.29 (t, 2 H), 3.58 (t, 2 H), 7.13 (dd, 1 H), 7.41 (m, 2 H), 8.45 (d, 1 H), 8.59 (b s, 1 H), 9.25 (s, 1 H). D. 2-(5-Pyrazin-2-yl-3-thiophen-2-yl-1H-pyrazol-4-yl)-ethylamine A mixture of the azide 1C (140 mg, 0.47 mmol), and palladium on carbon (10% w/w, 30 mg) in methanol (5 mL) was stirred under an atmosphere of hydrogen gas (1 atm, balloon) for 3 h. The reaction mixture was then flushed with nitrogen and the mixture filtered over celite. Concentration under reduced pressure gave the title compound (104 mg, 82% yield) as a yellow oil. MS m/e 272; HPLC retention time 1.57 min (Method A). E. 2-Chloroethanol (0.095 mL, 1.41 mmol) was added dropwise to a solution of chlorosulfonyl isocyanate (0.122 mL, 1.41 mmol) in dichloromethane at -20 C. The reaction mixture was warmed to 0 C. and maintained at that temperature 1.5 h. The solution was then transferred by canula to a solution of the amine XX (383 mg, 1.41 mmol) and triethylamine (1.38 ml, 9.9 mmol) in dichloromethane at -10 C. The reaction mixture was then stirred 17 h at room temperature under nitrogen to give a clear olive-green solution. A portion of the solution of intermediate sulfamolyoxazolidinone was concentrated to give a greenish solid (30 mg) which was taken up in acetonitrile (3 mL) and treated with triethylamine (0.059 mL, 0.42 mmol) and R-(1-benzyl-pyrrolidin-3-yl)-methyl-amine (0.013 mL, 0.046 mmol). The reaction mixture was heated at 70 C. 16 h, then concentrated and purified by reverse phase preparative HPLC to provide 25 mg of the title compound. MS m/e 525; HPLC retention time 2.31 min (Method A). 1H NMR (CD3OD): delta 1.95 (b s, 2H), 2.52 (b s, 2 H), 3.00 (s, 3 H), 3.10-3.40 (b m, 5 H), 4.15 (b s, 2 H), 4.20-4.40 (b m, 2 H), 6.96 (dd, 1 H), 7.20 (d, 1 H), 7.25 (m, 5 H), 7.33 (d, 1 H), 8.31 (s, 1 H), 8.44 (s, 1 H), 8.93 (s, 1 H). 1H NMR (CDCl3): delta 0.83 (t, 3H), 1.3 (dd, 2H), 1.39 (s, 9H), 1.40 (t, 2H), 1.45 (bm, 2H), 1.75 (bs, 2H), 2.1 (bs, 2H), 2.4 (bs, 2H), 2.76 (s, 3H)

The synthetic route of Pyrazine-2-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Ngu, Khehyong; Weinstein, David S.; Robl, Jeffrey A.; US2005/70589; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, 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 939412-86-9, Application In Synthesis of (3-Chloropyrazin-2-yl)methanamine hydrochloride

A mixture of (3-chloropyrazin-2-yl)methanamine hydrochloride (5 g, 21.38 mmol), (trans)-4- ((benzyloxycarbonylamino)methyl)cyclohexanecarboxylic acid (6.23 g, 21.38 mmol), 1 -ethyl-3-(3- dimethylaminopropyl) carbodiimide) hydrochloride (4.51 g, 23.52 mmol), 1 -hydroxy-7-azabenzotriazole (1.455 g, 10.69 mmol), and triethyl amine (4.76 ml, 34.2 mmol) in dichloromethane (60 ml) was stirred at room temperature overnight. The mixture was concentrated and the residue was purified by column chromatography (silica gel, dichloromethane with gradient 0.5 to 5% of methanol) to yield benzyl ((trans)-4- ((3-chloropyrazin-2-yl)methylcarbamoyl)cyclohexyl)methylcarbamate (8.79 g).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, (3-Chloropyrazin-2-yl)methanamine hydrochloride, and friends who are interested can also refer to it.

Reference:
Patent; N.V. ORGANON; MAN de,, Adrianus Petrus Antonius; REWINKEL,, Johannes Bernardus Maria; JANS,, Christiaan Gerardus Johannes Maria; RAAIJMAKERS,, Hans Cornelis Andreas; WIJKMANS,, Jacobus Cornelis Henricus Maria; WO2011/95556; (2011); 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 59303-10-5 as follows. Application In Synthesis of 2-Chloro-5-methylpyrazine

A mixture of N-cyclopropyl-4-oxazol-5-yl-N-piperidin-4-yl-benzamide (600 mg), 2-chloro-5-methyl-pyrazine (100 mg), and cesium carbonate (300 mg) in N,N-dimethylformamide (10 mL) is stirred for 3 days at 80 C. After cooling to room temperature ethyl acetate and water are added. The organic phase is separated, washed with water and brine, dried over MgSO4, and concentrated in vacuo. The residue is chromatographed on silica gel (ethyl acetate/methanol 7:3) to give the title compound. LC (method 1): tR=1.08 min; Mass spectrum (ESI+): m/z=404 [M+H]+.

According to the analysis of related databases, 59303-10-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NEUROCRINE BIOSCIENCES, INC.; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; NOSSE, Bernd; BLUM, Andreas; BREITFELDER, Steffen; HECKEL, Armin; HIMMELSBACH, Frank; LANGKOPF, Elke; WELLENZOHN, Bernd; ASHWEEK, Neil J.; HARRIOTT, Nicole; US2013/65906; (2013); 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. 274-79-3, name is Imidazo[1,2-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., category: Pyrazines

lmidazo[1 ,2-a]pyrazine (0.715 g, 6 mmol, Intermediate 1 ), 2-bromopyridine (0.644 ml_, 6.60 mmol), triphenylphosphine (0.315 g, 1.200 mmol), and palladium(ll) acetate (0.135 g, 0.600 mmol) were heated in Lambda/,Lambda/-dimethylacetamide (DMA) (8 ml.) at 150 0C for 5 hr in a microwave reactor. The bulk of the DMA was removed in vacuo and the residue partitioned between 10% isopropanol/DCM (100 ml) and saturated sodium bicarbonate solution (50 ml). Solids were removed by filtration through celite and the filtrated separated. The aqueous phase was extracted with 10% isopropanol/DCM (3 x 50 ml. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo to afford a crude oil, (2.6 g). The crude oil was partially purified by flash chromatography (Biotage SP4, 40+M, eluting with a 0-100% gradient of [(2M ammonia methanol/Ethyl acetate]/ethyl acetate) to afford material (1.59 g) which was repurified by flash chromatography (Biotage SP4, 40+M, eluting with a 0-100% gradient of [(2M ammonia methanol/Ethyl acetate]/ethyl acetate) to afford 3-(2-pyridinyl)imidazo[1 ,2-a]pyrazine (0.319 g, 1.626 mmol, 27.1 % yield).1H NMR (CDCI3, 400 MHZ) d 9.82 (dd, 1 H, J = 3.6, 1.2 Hz), 9.19 (d, 1 H, J = 1.6Hz), 8.72 (1 H, m), 8.03 (d, 1 H, J = 4.8 Hz), 7.84-7.91 m (2H), 7.29-7.21 m (2H).

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; GLAXO GROUP LIMITED; DEAN, David Kenneth; MUNOZ-MURIEDAS, Jorge; SIME, Mairi; STEADMAN, Jon Graham Anthony; THEWLIS, Rachel Elizabeth Anne; TRANI, Giancarlo; WALL, Ian David; WALTER, Daryl Simon; WO2010/125101; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 108-50-9, A common heterocyclic compound, 108-50-9, name is 2,6-Dimethylpyrazine, molecular formula is C6H8N2, 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.

The synthetic route chosen to synthesize certain compounds are illustrated below and in Figures 1A-D.

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; EMORY UNIVERSITY; GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.; SHIM, Hyunsuk; MOORING, Suazette Reid; BAI, Renren; (89 pag.)WO2017/11517; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, molecular formula is C5H7Cl2N3, 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. Computed Properties of C5H7Cl2N3

Intermediate 20. Step 7: (6R.8aS)-N-((3-chloropyrazin-2-yl)methyl)-2.2-dimethyl-3-oxooctahydroindolizine-6- carboxamide To a solution of (6R,8aS)-2,2-dimethyl-3-oxooctahydroindolizine-6-carboxylic acid (2.9 g, 13.74 mmol) in anhydrous DCM (137 mL) was added isopropyl carbonochloridate (2.02 g, 16.48 mmol) and Epsilon Nu (1.67 g, 16.48 mmol) at 0 C. The reaction mixture was stirred for 1 hour at room temperature. Then Epsilon Nu (2.78 g, 27.47 mmol) and (3-chloropyrazin-2-yl)methanamine hydrochloride (3.2 g, 17.86 mmol) was added , the reaction was stirred for 5 hours at room temperature. The solution was quenched with water, extracted with DCM and the combined organic layer was washed with water, brine and dried over anhydrous Na2SC>4. The organic layer was concentrated in vacuo. The crude was purified by silica gel column chromatography (PE/THF = 3/1) to afford (6R,8aS)-N-((3-chloropyrazin-2-yl)methyl)-2,2-dimethyl-3- oxooctahydroindolizine-6-carboxamide. 1H NMR (400 MHz, CDC13) delta ppm 1.08 – 1.28 (m, 6 H), 1.40 – 1.55 (m, 1 H), 1.70 – 1.91 (m, 2 H), 1.95 – 2.21 (m, 3 H), 2.36 (t, J = 12.4 Hz, 1 H), 2.87 (t, J= 12.4 Hz, 1 H), 3.40 (d, J = 7.6 Hz, 1 H), 4.32 (dd, Ji = 13.2, J2 = 3.2 Hz, 1 H), 4.70 (m, 2 H), 7.05 (s, 1 H), 8.32 (s, 1 H), 8.44 (s, 1 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 939412-86-9, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIU, Jian; KOZLOWSKI, Joseph, A.; ALHASSAN, Abdul-Basit; BOGA, Sobhana Babu; GAO, Xiaolei; GUIADEEN, Deodialsingh; WANG, Jyhshing; XU, Jiayi; YU, Wensheng; YU, Younong; CAI, Jiaqiang; LIU, Shilan; WANG, Dahai; WU, Hao; YANG, Chundao; (211 pag.)WO2016/109221; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 912773-21-8, 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. 912773-21-8, name is 2-Bromo-5-chloropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Preparation of ethyl 2-(5-chloropyrazin-2-yl)-2,2-difluoroacetate (39A) To a suspension of copper powder (244 g, 3877 mmol) in DMSO (5000 mL) was added ethyl 2-bromo-2,2-difluoroacetate (394 g, 1939 mmol) at ambient temperature. The reaction mixture was stirred at ambient temperature for 1 hour. 2-Bromo-5-chloropyrazine (250 g, 1292 mmol) was added to the reaction mixture portion-wise. The reaction mixture was stirred at ambient temperature for 3 hours. After the completion of reaction (monitored by TLC), the reaction mixture was quenched with aq. NH4C1 (2.0 L), filtrate through celite pad and filtrate was extracted with ethyl acetate (2 x 2 L). The combined organic extracts were dried over sodium sulfate and concentration under reduced pressure to get crude residue, which was purified by column chromatography (60-120 silica mesh, mobile phase 0- 2% ethyl acetate in hexane) affording ethyl 2-(5-chloropyrazin-2-yl)-2,2-difluoroacetate (39A) (215 g, 70% yield) as viscous clear liquid. lH NMR (400 MHz, DMSO-t/6) delta 9.05 (d, J = 1.4 Hz, 1H), 8.98 (dd, J= 1.4, 0.7 Hz, 1H), 4.39 – 4.34 (m, 2H), 1.24 (t, J= 7.1 Hz, 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, 2-Bromo-5-chloropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; AMGEN INC.; ALLEN, Jennifer, R.; AMEGADZIE, Albert; BOURBEAU, Matthew, P.; BROWN, James, A.; CHEN, Ning; FROHN, Michael, J.; LIU, Longbin; LIU, Qingyian; PETTUS, Liping, H.; QIAN, Wenyuan; REEVES, Corey, M.; SIEGMUND, Aaron, C.; (509 pag.)WO2017/24180; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 59489-71-3,Some common heterocyclic compound, 59489-71-3, name is 2-Amino-5-bromopyrazine, molecular formula is C4H4BrN3, 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 1; iV-(2-(4-(isopropylsulfonyl)phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)benza mide (Compound 1-1)METHOD A:Step 1: 5-(4-(Isopropylsulfonyl)phenyl)pyrazin-2-amine[00187] 5-Bromopyrazin-2-amine (5 g, 28.74 mmol), (4-isopropylsulfonylphenyl) boronic acid (7.866 g, 34.49 mmol) and K3P04 (12.20 g, 57.48 mmol) were combined in MeCN (100 mL) / Water (25 mL) and Pd[P(tBu)3]2 (734.4 mg, 1.437 mmol) was added. The reaction was heated at 60 C for 1 hour. The reaction mixture was cooled to ambient temperature and diluted with EtOAc and water. The layers were separated and the aqueous layer extracted with EtOAc (x 3). The combined organic layers were dried (MgS04), filtered andconcentrated in vacuo. The residue was triturated from DCM and isolated by filtration to give the sub-title compound as an orange solid (6.43 g, 76% Yield). ¾ NMR (400.0MHz, DMSO) delta 1.17 (d, 6H), 3.43 (sept, IH), 6.86 (s, 2H), 7.87 (d, 2H), 8.00 (s, IH), 8.20 (d, 2H) and 8.67 (s, IH) ppm; MS (ES+) 278.2.

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-5-bromopyrazine, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; MACCORMICK, Somhairle; STORCK, Pierre-henri; MORTIMORE, Michael, Paul; CHARRIER, Jean-damien; KNEGTEL, Ronald; YOUNG, Stephen, Clinton; PINDER, Joanne; DURRANT, Steven, John; WO2012/178123; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem