Tag: M.W=100-200

875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, 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. Recommanded Product: 2-Bromo-5H-pyrrolo[2,3-b]pyrazine

2-bromo-5H-pyrrolo[2,3-b]pyrazine (5 g, 25 mmol) was added to chlorosulfonic acid (20 mL) at 0C. The reaction was heated to 100-120C for 2.5 hours before cooling and pouring into ice-water (80 mL). The solution was extracted into EtOAc (2 x 100 mL), the organic layers combined, washed with brine, dried over sodium sulphate and concentrated in vacuo. The residue was added to a solution of isopropylamine (881 mg, 15 mmol) and triethylamine (2.66 g, 26 mmol) in DCM (60 mL) at 0C. The reaction was stirred at 0C for 3 hours, diluted with water (50 mL) and extracted into EtOAc (2 x 80 mL). The organic layers were combined, washed with brine, dried over sodium sulphate and concen- trated in vacuo. The solid was triturated with TBME to afford the title compound (2 g, 49% over 2 steps) as a brown solid that was used directly in the next step.

The synthetic route of 875781-43-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; THORARENSEN, Atli; BROWN, Matthew Frank; CASIMIRO-GARCIA, Agustin; CHE, Ye; FLANAGAN, Mark Edward; GILBERT, Adam Matthew; HAYWARD, Matthew Merrill; TELLIEZ, Jean-Baptiste; UNWALLA, Rayomand Jal; TRUJILLO, John I.; LIANG, Sidney Xi; (212 pag.)WO2016/178110; (2016); 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. 13535-07-4, name is 2-Amino-5-ethylpyrazine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2-Amino-5-ethylpyrazine

To a solution of (4S)-7-(6-methylpyridin-3-yl)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine (600 mg, 2.378 mmol), triphosgene (706 mg, 2.378 mmol) and triethylamine (1.989 mL, 14.27 mmol) in tetrahydrofuran (THF) (15 mL) stirred under nitrogen at room temperature for 30 min was added 5-ethylpyrazin-2-amine (879 mg, 7.13 mmol). The reaction mixture was stirred at 70 C. for 16 h and cooled to room temperature and then the reaction mixture was poured in to water and extracted with EtOAc (3×15 mL). The combined organic layers were washed with water, brine solution, dried over sodium sulfate and evaporated to give crude compound (TLC eluent: 5% MeOH in DCM: Rf-0.1; UV active). The crude compound was purified by column chromatography using Neutral Alumina and eluted with 30% EtOAc/Pet ether to afford pure (4S)-N-(5-ethylpyrazin-2-yl)-7-(6-methylpyridin-3-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (383 mg, 0.953 mmol, 40.1% yield), LCMS (m/z): 402.3 [M+H]+. 1H NMR (400 MHz, CDCl3): delta ppm 13.65 (s, 1H) 9.41 (d, J=1.53 Hz, 1H) 9.11 (d, J=2.19 Hz, 1H) 8.41 (dd, J=8.22, 2.52 Hz, 1H) 8.22 (d, J=1.32 Hz, 1H) 7.61 (d, J=7.89 Hz, 1H) 7.40 (d, J=8.11 Hz, 1H) 7.32 (d, J=8.11 Hz, 1H) 5.70 (dd, J=6.03, 3.18 Hz, 1H) 3.34-3.13 (m, 3H) 3.02 (dd, J=12.06, 3.29 Hz, 1H) 2.83 (q, J=7.53 Hz, 2H) 2.64 (s, 3H) 2.40-2.34 (m, 1H) 2.15-2.03 (m, 1H) 1.33 (t, J=7.56 Hz, 3H).

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 13535-07-4.

Reference:
Patent; BLUM, Charles A.; Caldwell, Richard Dana; Casaubon, Rebecca; Disch, Jeremy S.; Fox, Ryan Michael; Koppetsch, Karsten; Miller, William Henry; NG, Pui Yee; Oalmann, Christopher; Perni, Robert B.; Szczepankiewicz, Bruce G.; White, Brian; US2015/152108; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 59303-10-5,Some common heterocyclic compound, 59303-10-5, name is 2-Chloro-5-methylpyrazine, molecular formula is C5H5ClN2, 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.

NaH (60% in mineral oil, 103 mg, 2.57 mmol) was added to a stirred solution of l-Boc- 4-hydroxypiperidine (CAS: 109384-19-2; 470 mg, 2.33 mmol) in DMF (10 mL) at 0 C under N2 atmosphere. The mixture was stirred at room temperature for 1 h. 2-Chloro-5- methylpyrazine (CAS: 59303-10-5; 300 mg, 2.33 mmol) was added to the mixture under N2 atmosphere and the reaction mixture was stirred at 50 C for 16 h. A solution of 1- Boc-4-hydroxypiperidine (CAS: 109384-19-2) in DMF which was stirred for 1 h at room temperature was added, and the reaction mixture was stirred at 80 C for another 16 h. The mixture was diluted with water and extracted with DCM. The organic layer was dried (MgS04), filtered and the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica, heptane/EtOAc, gradient from 100:0 to 80:20). The desired fractions were collected and concentrated in vacuo to afford intermediate 151 (320 mg, 47%) 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 2-Chloro-5-methylpyrazine, its application will become more common.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; BARTOLOME-NEBREDA, Jose Manuel; TRABANCO-SUAREZ, Andres, Avelino; DE LUCAS OLIVARES, Ana Isabel; DELGADO-JIMENEZ, Francisca; CONDE-CEIDE, Susana; VEGA RAMIRO, Juan, Antonio; (245 pag.)WO2019/243530; (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. 41110-29-6, name is Methyl 3-methylpyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., COA of Formula: C7H8N2O2

A solution of methyl 3-methylpyrazine-2-carboxylate (9.1 g, 59.8 mmol) in DCM (100 mL) was cooled to 0 C. was added urea hydrogen peroxide adduct (7.8 g, 83.0 mmol), followed by dropwise addition of trifluoroacetic acid anhydride (10.8 mL, 78.0 mmol). The resulting mixture was stirred at 0 C. for 1 h, and at RT for 18 h, during which LCMS indicated a mixture of two peaks corresponding to MS m/z=169.0 [M+H]+. The reaction was diluted with DCM and quenched with saturated Na2SO3 solution; the aqueous layer was back-extracted with DCM (2×). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. ISCO purification (20-80% EtOAc/hexanes) afforded a mixture of two regioisomers, containing 3-(methoxycarbonyl)-2-methylpyrazine 1-oxide and 2-(methoxycarbonyl)-3-methylpyrazine 1-oxide (5.2 g, 30.9 mmol, 51.7% yield). The mixture of regioisomers was taken to next step without further purification. MS m/z=169.0 [M+H]+. A solution of the mixture of 3-(methoxycarbonyl)-2-methylpyrazine 1-oxide and 2-(methoxycarbonyl)-3-methylpyrazine 1-oxide (5.1 g, 15.2 mmol) in toluene (50 mL) was cooled to 0 C. and phosphorus oxychloride (2.8 mL, 30.3 mmol) was added under nitrogen followed by DMF (0.12 mL, 1.52 mmol). The reaction mixture was stirred at RT for 4 h, and heated to 65 C. for 18 h, cooled to RT, diluted with EtOAc and washed with saturated NaHCO3 solution. The aqueous layer was back-extracted with EtOAc (2×). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. ISCO purification (0-50% EtOAc/hexanes) with care afforded both isomers: methyl 5-chloro-3-methylpyrazine-2-carboxylate (0.68 g) (minor product) denoted by peak 1 and methyl 6-chloro-3-methylpyrazine-2-carboxylate (1.50 g) (major product) denoted by peak 2. MS m/z=187.0 [M+H]+. Peak 1: 1H NMR (300 MHz, DMSO-d6) delta 8.73 (s, 1H), 3.91 (s, 3H), 2.71 (s, 3H). Peak 2: 1H NMR (300 MHz, DMSO-d6) delta 8.89 (s, 1H), 3.91 (s, 3H), 2.71 (s, 3H).

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; LEWIS, Richard T.; ALLEN, Jennifer R.; BROWN, James; GUZMAN-PEREZ, Angel; HUA, Zihao; JUDD, Ted; LIU, Qingyian; OLIVIERI, Philip R.; ROMERO, Karina; SCHENKEL, Laurie; STELLWAGEN, John; WHITE, Ryan; US2015/38497; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 5521-58-4, 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. 5521-58-4, name is 5-Methylpyrazin-2-amine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 5-methylpyrazin-2-amine (5.00g, 45.8 mmol) and pyridine (4.35g,55.0 mmol) in DCM (250 mL) was added bromine (8.80 g, 55.0 mmol). The mixture was stirredat rt overnight. To the reaction mixture was added water (150 mL), and the resulting mixture waspartitioned. The organic layer was washed with saturated brine (100 mL), dried over anhydroussodium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound asa yellow solid (7.64 g, 88 %).MS (ESI, pos. ion) m/z: 190.2 [M+Ht;1H NMR (400 MHz, CDCh) 8 (ppm): 7.83 (s, lH), 4.93 (s, 2H), 2.41 (s, 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, 5-Methylpyrazin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; TANG, Changhua; REN, Qingyun; YIN, Junjun; YI, Kai; LEI, Yibo; WANG, Yejun; ZHANG, Yingjun; (303 pag.)WO2018/108125; (2018); 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 912773-21-8 as follows. Recommanded Product: 912773-21-8

2-chloro-5-bromopyrazine (4.0 mmol) in CHC13 (40 mL), stirring under nitrogen, BPO (0.08 mmol) and NBS (4.4 mmol) were added to the reaction mixture, heated to reflux for 5 h, cooled . The solvent was distilled off under reduced pressure to give a crude product. A solution of morpholine (0.50 mol) in ethanol was added to the crude product of the previous step under nitrogen and stirred at room temperature overnight.The solvent was removed under reduced pressure.The crude product was purified by column chromatography to give 4-(4-bromo-2-fluorophenyl)morpholine.

According to the analysis of related databases, 912773-21-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Ocean University of China; Shao Changlun; (69 pag.)CN108658937; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

21279-62-9, name is 3-Chloropyrazine-2-carboxamide, 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. Safety of 3-Chloropyrazine-2-carboxamide

General procedure: The starting compound (1.27 mmol) was treated with 18 aliphatic amines, alicyclic amines or saturated heterocycles containing at least one nitrogen atom (2.54 mmol). Four reactions were completed by conventional heating methods. The conditions were 110 C, toluene as a solvent and pyridine (1.27 mmol) as a base. The reaction time was set to one hour. Then the reactions were completed using the microwave reactor with focused field and conditions used for syntheses were 140 C, 30 min,120 W, methanol used as a solvent and pyridine (1.27 mmol) as a base. They were set experimentally with respect to prior experience. The progress of reaction was monitored with TLC in system hexane/ethyl acetate (1:1). Then the mixture was separated by flash column chromatograph using gradient elution. Mobile phases were hexane and ethyl acetate again.

The synthetic route of 21279-62-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Jandourek, Ondrej; Dolezal, Martin; Kunes, Jiri; Kubicek, Vladimir; Paterova, Pavla; Pesko, Matus; Buchta, Vladimir; Kralova, Katarina; Zitko, Jan; Molecules; vol. 19; 7; (2014); p. 9318 – 9338;,
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. 6863-74-7, name is 6-Chloropyrazine-2-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C5H2ClN3

c) Preparation of N-(6-chloro-pyrazin-2-ylmethyl)-2,2-dimethyl-propionamideThe preceding intermediate (8.8 g, 62.8 mmol) was hydrogenated under standard conditions in ethanol (75 mL) and in the presence of Raney nickel (3.6 g, 62.8 mmol), as well as di-tert-butyldicarbonate (14.4 g, 66 mmol) over 18 h. The catalyst was filtered off over Celite, the filtrated was concentrated in vacuo and chromatographed over silica gel to afford the desired Boc-protected amine (6.7 g, 27.6 mmol, 63%)

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 6863-74-7.

Reference:
Patent; BASF SE; WO2009/112523; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 91476-80-1, 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. 91476-80-1 name is 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine, 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.

Compound 2A (126.0mg, 0.48mmol) was dissolved in 10.0ml acetonitrile, Ar gas protection. Compound 3a-1 (118.0mg, 0.96mmol), and lithium perchlorate (102.0mg, 0.96mmol), the reaction mixture was heated to 80 deg. C, the reaction after 20 hours, cooled to room temperature.The reaction mixture was evaporated to dryness and the residue with CH2Cl2Dissolved, the organic phase was washed 3 times with saturated NaCl solution, dried over anhydrous Na2SO4Dried, filtered, and evaporated to dryness and the residue was separated by column chromatography (dichloromethane: methanol = 100: 1-50: 1), to give a compound 80.8mg as a white solid, mp: 86-88 deg. C, a yield of 45.0%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; Chinese Academy of Sciences, Shanghai Institute of Medicine; Nanjing Changao Pharmaceutical Technology co., LTD; YANG, YU SHE; CAO, XU FENG; LI, ZHAN; LI, WEI; (78 pag.)CN103965194; (2016); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 14508-49-7,Some common heterocyclic compound, 14508-49-7, name is 2-Chloropyrazine, molecular formula is C4H3ClN2, 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.

b) 2 4-Methylpiperazin-1-yl)-/V-pyrazin-2-yl-2,4′-bipyridin-6-amine; An oven dried resealable Schlenk tube was charged with 2′-(4-methylpiperazin-1-yl)- 2,4′-bipyridin-6-amine (example 34a, 0.09 g, 0.33 mmol), 2-chloropyrazine (0.04 mu, 0.39 mmol), sodium terf-butoxide (0.04 g, 0.38 mmol) and dioxane (1 ml_). The Schlenk tube was subjected to three cycles of evacuation-backfilling with argon, and tris(dibenzylideneacetone)dipalladium(0) (0.01 g, catalytic amount) and 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (0.01 g, catalytic amount) were added. After three further cycles of evacuation-backfilling with argon, the Schlenk tube was capped and placed in an oil bath at 95 C. After 16h, the mixture was cooled and the solvent was removed in vacuo. The residue was purified by flash chromatography to give the title compound (0.09 g, 82%) as a solid.LRMS (m/z): 348 (M+1)+.1 H NMR (500 MHz, CHLOROFORM-d) delta ppm 2.35 (s, 3 H) 2.53 – 2.55 (m, 4 H) 3.63 – 3.66 (m, 4 H) 7.16 (dd, =6.50, 2 Hz, 1 H) 7.34 (s, 1 H) 7.39 (d, J=9.00 Hz, 1 H) 7.61 (d, J=10.00 Hz, 1 H) 7.73 (t, J=10.00 Hz, 1 H) 7.96 (br. s., 1 H) 8.13 (d, J=3.50 Hz, 1 H) 8.19 – 8.21 (m, 1 H) 8.13 (d, J=3.50 Hz, 1 H) 8.98 (d, J=2.00 Hz, 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 2-Chloropyrazine, its application will become more common.

Reference:
Patent; ALMIRALL, S.A.; VIDAL JUAN, Bernat; FORNS BERENGUEL, Maria Pilar; CASTILLO MCQUADE, Marcos; ERRA SOLA, Montserrat; MIR CEPEDA, Marta; WO2012/41476; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem