Pyrazines

Reference of 33332-29-5,Some common heterocyclic compound, 33332-29-5, name is 2-Amino-5-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.

To a solution of 48 (20 g, 0.157 mol) in DMF was added NIS (69.2 g, 0.31 mol) at 20C under N2. The reaction solution was heated to 75C and stirred for 16 h. TLC (PE: EtOAc =3:1 ) showed the reaction was completed. The reaction solution was extracted with EtOAc (200 ml. x 3) from water (300 ml_). The organic phase was washed with a.q. Na2S203 (300 ml.) and brine (300 ml_). Dried over Na2S04, filtered and purified by silica gel chromatography (gradient EtOAc : PE = from 1 :10 to 1 : 1 ) to give 49 (20 g, 50%). (0661) 1 H NMR 49 CDCIs Varian 400MHz: delta 4.83 – 5.23 (m, 2 H) 7.82 – 8.01 (m, 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-Amino-5-chloropyrazine, its application will become more common.

Reference:
Patent; BASF SE; RHEINHEIMER, Joachim; RATH, Rakesh; KULKARNI, Sarang; ROSENBAUM, Claudia; WIEBE, Christine; BRAHM, Lutz; SIEPE, Isabella; HADEN, Egon; ROEHL, Franz; KHANNA, Smriti; SCHIFFER, Helmut; KREMZOW-GRAW, Doris; POONOTH, Manojkumar; (285 pag.)WO2019/57660; (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. 762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, A new synthetic method of this compound is introduced below., Recommanded Product: 762240-92-6

A round bottom flask is charged with 2,4,5-thfluorophenylacetic acid (25 g),Meldrums acid (20.5 g), N,N-dimethylaminopyhdine (1.28 g), and acetonitrile (75 ml_). Diisopropylethylamine (47.28 ml_) is added drop-wise, while maintaining the temperature below 500C. The mixture is heated to 500C, followed by drop-wise addition of pivalolyl chloride (17.8 ml_) over about 45 minutes. The mixture is maintained at the same temperature with stirring for 3 hours, followed by addition of thazole hydrochloride (30 g) in one portion. Subsequently, thfluoroacetic acid (2.95 ml_) is added and the mixture is maintained at 55C for another 6 hours. The mixture is cooled to room temperature, followed by distillation to remove acetonitrile and afford a residue. Water (100 ml_) and ethyl acetate (500 ml_) are added to the residue, and the organic layer is separated. The organic layer is washed with 5% sodium bicarbonate, then brine solution (50 ml_), and is dried over sodium sulphate, followed by distillation at 400C to form a ketoamide, i.e., 4- oxo-4-[3-(thfluoromethyl)-5,6-dihydro[1 ,2,4]thazolo[4,3a]pyrazin-7(8H)-yl]-1 -(2,4,5- trifluorophenyl)butan-2-one. lsopropyl alcohol (75 ml_) and (R)-(+)-1 – phenylethylamine (18.64 ml_) are added and the mixture is heated to 45-50C for 4 hours. The isopropyl alcohol is distilled completely below 40C to form a residue. Dichloromethane (200 ml_) and water (100 ml_) are mixed with the residue, followed by separation of the organic layer. The aqueous layer is extracted with dichloromethane (200 ml_). The organic layers are combined, washed with brine, dried over sodium sulphate, and distilled to afford a residue, which, on purification results in the title compound (28.7g, 42.8% yield).

The synthetic route of 762240-92-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; DR. REDDY’S LABORATORIES LTD.; DR. REDDY’S LABORATORIES, INC.; BANDICHHOR, Rakeshwar; GUDIMALLA, Nagaraju; DWIVEDI, Namrata; CHETLURU, Kiran Kumar; GADE, Srinivas Reddy; MUVVA, Venkateswarlu; SRIVASTAVA, Bindu; WO2011/25932; (2011); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 344940-70-1, These common heterocyclic compound, 344940-70-1, name is 5-Bromo-3-phenylpyrazin-2-amine, 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.

[00184] To a solution of 5-bromo-3-phenylpyrazin-2-amine (26 mg, 0.1 mmol) and tert-butyl isopropyl(5-(tributylstannyl)thiazol-2-yl)carbamate (80 mg, 0.15 mmol) in DMF (0.4 mL) was added PdCl2(PPh3)2 (7 mg, 0.01 mmol) followed by DIPEA (0.044 mL, 0.25 mmol) and the reaction heated at 85 0C for 18h. The reaction mixture was cooled to room temperature and diluted with EtOAc (6 mL) and water (2 mL). the layers were separated and the aqueous layer further extracted with EtOAc. The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The product was isolated via column chromatography (SiO2, 25% EtO Ac/heptane) to afford the product (44 mg, 100% yield).

The synthetic route of 344940-70-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; WO2009/155389; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

6164-79-0, name is Methyl 2-pyrazinecarboxylate, 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: Methyl 2-pyrazinecarboxylate

d Pyrazine-2-hydrazide To a solution of the product from Example 1 step c) (22 g, 159 mmol) in methanol (250 ml) was slowly added hydrazine monhydrate (36.6 ml, 710 mmol). The reaction mixture was stirred for 1.5 h. The precipitate produced was filtered, washed with diethyl ether and dried in the oven at 80 C. to give the required product (30 g). 1H NMR (250 MHz, DMSO) delta 4.66 (2H, broad peak), 8.66 (1H, m), 8.84 (1H, d, J=2.5 Hz), 9.13 (1H, d, J=2.5 Hz), 10.15 (1H, broad peak); MS (ES+) m/e 139 [MH+].

The synthetic route of 6164-79-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Merck Sharp & Dohme Ltd.; US6297235; (2001); B1;,
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., HPLC of Formula: C4H4BrN3

5-Bromopyrazin-2-amine (0.11g, 0.63 mmol) was dissolved in NaOMe/MeOH (0.23g Na metal in 10 ml_ MeOH) and heated by microwave irradiation at 14O0C for 7 hours. After evaporation of the solvent, the residue was purified by preparative TLC, eluting with 30% ethyl acetate – n-hexane, to give 5-methoxypyrazin-2-amine (25 mg, 32%).1H NMR (500 MHz, MeOD) delta 7.64 (1H, s), 7.58 (1H, s), 3.85 (3H, s). LCMS (3) Rt 1.75 min; m/z (ESI+) 126 (MH+).

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; CANCER RESEARCH TECHNOLOGY LIMITED; WO2009/44162; (2009); 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. 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, A new synthetic method of this compound is introduced below., Formula: C6H7N3O2

General procedure: Used for N-benzyl derivatives 1-8. The starting 3-aminopyrazine-2-carboxylic acid(Sigma-Aldrich, Schnelldorf, Germany; 2.2 g; 15.8 mmol) in methanol (250 mL) was cooled downto 0 C and concentrated H2SO4 (3.2 mL) was added. The reaction mixture was stirred for 48 h atrt. Subsequently the reaction mixture was poured into water (27 mL) and alkalized by NaHCO3(approx. 6.3 g) to pH = 7. The precipitate was filtered off and collected as white-brown solid toobtain methyl 3-aminopryzine-2-carboxylate [32]. Methyl 3-aminopyrazine-2-carboxylate (100 mg;0.65 mmol) in methanol (2 mL) along with substituted benzylamine (1.95 mmol; 3 equiv) and NH4Cl(10 mg; 0.19 mmol; 0.1 equiv) [33] were put into reaction tube used for microwave assisted synthesiswith a magnetic stirrer. Reaction was performed in a CEM Discover microwave reactor with a focusedfield in pressurized vials with the following settings: 130 C, 90 W and 40 min. The progress of thereaction was checked using TLC (Merck Silica 60 F254) developed by in hexane/ethyl-acetate 2:1 system.The reaction mixture was adsorbed to silica gel and purified by flash chromatography (Teledyne IscoInc.,) using silica (irregular, 40-63 m) as a stationary phase and gradient elution EtOAc in hexane0-100%, with respect to the expected lipophilicity of the product.

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; Bouz, Ghada; Semelkova, Lucia; Jand?ourek, Ond?ej; Kone?na, Klara; Paterova, Pavla; Navratilova, Lucie; Kubi?ek, Vladimir; Kune?, Ji?i; Dole?al, Martin; Zitko, Jan; Molecules; vol. 24; 7; (2019);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 33332-28-4, name is 2-Amino-6-chloropyrazine, 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 33332-28-4, HPLC of Formula: C4H4ClN3

6-Morpholinop razin-2-amineA stirred solution of 6-chloropyrazin-2-amine (0.225 g, 1.74 mmol) and morpho- line (0.227 g, 2.61 mmol) was heated at 100 C for 22 h. After cooling to 23 C, water was added to the mixture and extracted with EtOAc. The combined organics were concentrated in vacuo. The crude mixture was purified on alumina (0-50% EtOAc in hexane) to give the desired product 6-morpholinopyrazin-2- amine. Mass Spectrum (ESI) m/e = 181.1 (M + 1).

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-Amino-6-chloropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; AMGEN INC.; DRANSFIELD, Paul John; GONZALEZ LOPEZ DE TURISO, Felix; PATTAROPONG, Vatee; SIMARD, Jillian L.; WO2012/3264; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 330786-09-9, These common heterocyclic compound, 330786-09-9, name is Methyl 3,5-dichloropyrazine-2-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.

To a solution of 3,5-dichloro-pyrazine-2-carboxylic acid methyl ester (1.20 g, 5.82 mmol) in dimethylformamide (12 ml) is added potassium carbonate (0.96 g, 6.98 mmol) at RT followed by the addition of morpholine (0.5 ml, 5.82 mmol). The resulting mixture is stirred at RT for 3 h. After completion of the reaction, the mixture is diluted with water (20 ml) and extracted with EtOAc (3 x 30 ml). The combined organic layers are washed with water (30 ml), brine (30 ml), dried over anhydrous sodium sulfate and evaporated in vacuo to get the crude product, which is purified by column chromatography (silica gel, 10% acetone/hexane) to yield 3-chloro-5-morpholin-4-yl-pyrazine-2-carboxylic acid methylester (1.10 g, 4.28 mmol, 73%).

Statistics shows that Methyl 3,5-dichloropyrazine-2-carboxylate is playing an increasingly important role. we look forward to future research findings about 330786-09-9.

Reference:
Patent; GRUeNENTHAL GMBH; LUCAS, Simon; KUHNERT, Sven; BAHRENBERG, Gregor; SCHROeDER, Wolfgang; WO2014/82739; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, 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. HPLC of Formula: C6H8ClF3N4

General procedure: A solution of 3-(trifluoromethyl)-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyrazine hydrochloride salt 9 (1.0 eq.) in dimethylformamide (DMF, 2e3 mL) was added potassium carbonate (2.5eq.) at 5 C and stirred for 15 min at room temperature. To this,various chloride derivatives (1.0 eq.) in DMF was added to reaction mixture at same temperature. The resultant reaction mixture was allowed to stir at room temperature for 24 h. The completion of the reaction was monitored on TLC (using 10% MeOH: DCM and ammonia as a modifier as mobile phase). The reaction mixture was poured into ice-cold water and extracted with ethyl acetate(2 x 15 mL). Organic layers were combined and the combined organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford crude material and crystallized it from methanol to get 3-(trifluoromethyl)-5,6,7,8-tetrahydro [1,2,4]triazolo [4,3-a]pyrazine derivatives (12f-12j) in good practical yield.

The synthetic route of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride has been constantly updated, and we look forward to future research findings.

Reference:
Article; Jethava, Divya J.; Acharya, Prachi T.; Vasava, Mahesh S.; Bhoi, Manoj N.; Bhavsar, Zeel A.; Rathwa, Sanjay K.; Rajani, Dhanji P.; Patel, Hitesh D.; Journal of Molecular Structure; vol. 1184; (2019); p. 168 – 192;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 33332-28-4, 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. 33332-28-4 name is 2-Amino-6-chloropyrazine, 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.

Example 29: Preparation of:2-(4-Ch]oro-2-mophiholin-4-yl-1.24hiazol-5-yl)-5-(dicvcloprorhoyImethylV3,7-dimethyl-5H-pyitauolof2.3- ipyrazine; Part A: 2-Amino-6-methy] pyrazine; A solution of zinc chloride (2.0M in THF, 96.5 mL, 48.2 mmol, 5.0 equiv.) is treated dropwise with methylmagnesium bromide (3.0 M in Et2O, 32.2 mL, 96.5 mmoi, 10.0 equiv.) at 0 °C. The mixture is wanned to room temp and stirred for 45 min. A solution of 2-amino-6-chloro pyrazine (1.25 g. 9.65 mmol, 1.0 equiv) and NiC12(dppp) (157 mg, 0.29 mmol, 0.03 equiv) in THF (15 mL) is added to the freshly prepared dimethylzinc reagent. The reaction mixture is stirred under for 3h and cooied to room temp. The reaction is quenched carefully with sat’d NH4CI solution and allowed to stir overnight. The layers are separated and the aqueous layer is extracted with EtOAc (2 X 30 mL). The combined organic extracts are washed with brine, dried over Na2Spsi4 and concentrated under reduced pressure to give a cream-colored solid that is used without further purification. MS = 110.08 (M +1). 1H NMR (400 MHz, CDCI3) delta 7.78 (IH, s), 7.72 (IH, s), 4.59 (2H, bs), 2.35 (3H, s).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Amino-6-chloropyrazine, and friends who are interested can also refer to it.

Reference:
Patent; NEUROGEN CORPORATION; WO2008/83070; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem