Month: September 2021

6966-01-4, 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. 6966-01-4 name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, 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.

Methyl beta-bromo-S-chloropyrazine-l-carboxylate (1-2)To a suspension of copper (II) chloride (3.48 g, 25.9 mmol, 2.0 equiv) in acetonitrile (43 mL) was added te/t-butylnitrite (3.06 mL, 25.9 mmol, 2.0 equiv). The reaction was heated to 600C for 30 minutes and then cooled to ambient temperature. To this suspension was added methyl 3-amino-6-bromopyrazine-2-carboxylate (Ll, 3.O g, 12.9 mmol, 1.0 equiv, commercially available from SynChem Inc.) as a solid in portions with gas evolution. The reaction mixture was heated to reflux for 18 hours and the reaction was cooled to ambient temperature. The reaction was partitioned between EtOAc and saturated NaHCO3. The organic phase was washed with NaHCO3 and dried over MgSO4. After concentration, the residue was purified by normal phase column chromatography (0 to 50% EtOAc in hexanes) to afford the product CL2) as a clear oil. ESI+ MS [M+H]+ C6H4BrClN2O2: 250.7 found, 250.9 required.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-amino-6-bromopyrazine-2-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; MERCK SHARP &; DOHME CORP.; MERCER, Swati, P.; ROECKER, Anthony, J.; WO2010/141275; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route 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.

Step B: Preparation of 2-Hydrazinylpyrazine.Under nitrogen atmosphere, 2-chloropyrazine (96 mL, 1073 mmol) was added dropwise to 35 wt aqueous hydrazine (544 mL, 6009 mmol) at 65 C over 1 h. After the addition, stirring was continued at 63-67 C for 16 h and the reaction mixture was let stand at room temperature for two days. The mixture was filtered to remove a small amount of precipitate, then extracted with 10% iPrOH/dichloromethane (5 x 250 mL). The combined organic extracts were dried (MgS04), filtered, then concentrated under reduced pressure. The resulting solid was triturated with isopropyl acetate (600 mL). The solid was collected by filtration, rinsed with isopropyl acetate, then dried in vacuo to give the title compound (60 g) as a pale yellow solid. LCMS m/z = 111.2 [M+H]+; lU NMR (400 MHz, DMSO- ) delta 4.21 (s, 2H), 7.70 (d, 7 = 2.8 Hz, 1H), 7.89 (s, 1H), 7.93 (dd, 7 = 2.8, 1.5 Hz, 1H), 8.10 (d, 7 = 1.5 Hz, 1H).

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; ARENA PHARMACEUTICALS, INC.; THATTE, Jayant; BLACKBURN, Anthony C.; HAN, Sangdon; JONES, Robert M.; JUNG, Jae-Kyu; MONTALBAN, Anthony Garrido; PAL, Biman B.; RUETER, Jaimie Karyn; STRAH-PLEYNET, Sonja; THORESEN, Lars; XIONG, Yifeng; YUE, Dawei; ZHU, Xiuwen; WO2012/116279; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 274-79-3,Some common heterocyclic compound, 274-79-3, name is Imidazo[1,2-a]pyrazine, molecular formula is C6H5N3, 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 imidazo[1,2-a]pyrazine (7.2 g, 60.44 mmole) was dissolved in 2-methoxyethanol (100 ml) and PtO2 (1.2 g, 5.13 mmole) was added. The reaction mixture was stirred overnight at RT in an autoclave under a hydrogen atmosphere (4 bar). The autoclave was then flushed with nitrogen, the reaction mixture was filtered through filter earth, concentrated, and the solvent residues were then extracted with toluene. Purification was carried out by column chromatography on silica gel (DCM/7 N NH3 in methanol, 95:5)

The synthetic route of 274-79-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GRUENENTHAL GmbH; US2009/186899; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 939412-86-9,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.

To trichloromethyl chloroformate (4.19 mmol, 0.505 ml) in ethyl acetate (5 ml) at 0 C was added dropwise 1 ,4-dioxa-8-azaspiro[4.5]decane (6.98 mmol, 0.895 ml) in ethyl acetate (5ml) and N,N- diisopropylethylamine (6.98 mmol, 1.217 ml). After one hour the mixture was concentrated, the residue was dissolved in dichloromethane (25 ml) and 2-aminomethyl-3-chloropyrazine hydrochloride (content 60%; 10.00 mmol, 3 g) and triethylamine (27.9 mmol, 3.89 ml) were added. After stirring for 16 hours at room temperature the reaction mixture was diluted with water, filtered over decalite, washed with water, filtered over a phase separation filter and concentrated in vacuo. The crude product was dissolved in dichloromethane containing 1 % triethylamine and purification by column chromatography (silica gel; dichloromethane containing 1 % triethylamine) gave N-((3-chloropyrazin-2-yl)methyl)-1 ,4-dioxa-8- azaspiro[4.5]decane-8-carboxamide (1.5 g).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (3-Chloropyrazin-2-yl)methanamine hydrochloride, its application will become more common.

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

Electric Literature of 5521-55-1, These common heterocyclic compound, 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, 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.

In methanol (15 ml), 5-methylpyrazine-2-carboxylic acid (manufactured by Tokyo Kasei Kogyo Co., Ltd.) (1.25 g) was dissolved. Then, the solution was added with WSCI hydrochloride (2.59 g) and N,N-dimethylaminopyridine (1.65 g) in this order, followed by stirring at room temperature for 3 hours. The reaction solution was added with water and then extracted with chloroform. The organic layer was washed with saturated saline solution and then dried with anhydrous sodium sulfate. The solvent was distilled off and the resulting crude product was then purified through silica gel column chromatography (chloroform/methanol). The purified product was dissolved in ethanol (15 ml) and THF (8 ml) and added with calcium chloride (1.11 g). After that, the reaction solution was cooled to 0C and then gradually added with sodium borohydride (757 mg), followed by stirring at room temperature for 19 hours. The reaction solution was added with a 1 mol/l citric acid solution (40 ml), followed by extraction with ethyl acetate. The organic layer was washed with saturated saline solution and then dried with anhydrous sodium sulfate, followed by distilling the solvent off. The residue was dissolved in chloroform (10 ml) and then added with manganese dioxide (chemically processed product) (2.2 g), followed by stirring at room temperature for 1 hour. After completion of the reaction, the catalyst was filtrated out through Celite and the solvent was then distilled off. The crude product obtained was purified through silica gel column chromatography (chloroform/methanol), thereby obtaining the subject compound (35.9 mg) as a colorless oily substance.

The synthetic route of 5521-55-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Kureha Chemical Industry Co., Ltd.; EP1550657; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

622392-04-5, name is 2-Bromo-5-iodopyrazine, 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. Quality Control of 2-Bromo-5-iodopyrazine

Preparation of compound 22a: 2-(2,2-difluoroethoxy)-5-iodopyrazineTo a solution of 2,2-difluoroethanol (0.74 g, 8.7 mmol) in THF (5OmL) at room temperature was added sodium butoxide (1.13 g, 11.4 mmol) and stirred for 15 min. The reaction mixture was cooled to 0 0C and a solution of 2-bromo-5-iodopyrazine (2.5 g, 8.7 mmol) in THF (50 ml_) was added slowly over 5 min. The reaction mixture was allowed to warm to room temperature and stirred for 16 h. The mixture was diluted with ethyl acetate and washed with sat. NH4CI. The organic layer was dried over MgSO4, filtered and concentrated which gave the title compound 22a (2.3 g, 90%).

The synthetic route of 622392-04-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; NINKOVIC, Sacha; BRAGANZA, John Frederick; COLLINS, Michael Raymond; KATH, John Charles; LI, Hui; RICHTER, Daniel Tyler; WO2010/16005; (2010); 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. 622392-04-5, name is 2-Bromo-5-iodopyrazine, A new synthetic method of this compound is introduced below., Formula: C4H2BrIN2

Step 1: N-1-(5-Iodo-pyrazin-2-yl)-2-methyl-propane-1,2-diamine To a solution of 2-bromo-5-iodopyrazine (CAS 622392-04-5) (250 mg, 878 mmol) in 0.7 ml of pyridine, was added 2-methylpropane-1,2-diamine (116 mg, 138 mul, 1.32 mmol, 1.5 equiv.) at room temperature. The colorless solution was stirred for 16 hours at 100 C. The reaction mixture was cooled and concentrated in vacuo. The crude material was used directly in the next step.

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; Green, Luke; Guba, Wolfgang; Jaeschke, Georg; Jolidon, Synese; Lindemann, Lothar; Ricci, Antonio; Rueher, Daniel; Stadler, Heinz; Vieira, Eric; US2011/251169; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 850349-42-7, 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. 850349-42-7, name is Methyl imidazo[1,2-a]pyrazine-8-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

PREPARATIVE EXAMPLE 10; Commercially available Imidazo[l,2-a]pyrazine-8-carboxylic acid methyl ester (337 mg) was dissolved in 1,4-dioxane (25 ml) and H2O (58 ml) and treated with 1 M NaOH (2.4 ml). The mixture was stirred at room temperature for 45 Min and the solvents evaporated to afford the crude title compound (MH+ = 164).

The chemical industry reduces the impact on the environment during synthesis Methyl imidazo[1,2-a]pyrazine-8-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ALANTOS PHARMACEUTICALS HOLDING, INC.; WO2008/63669; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 54608-52-5,Some common heterocyclic compound, 54608-52-5, name is 2-Hydrazinopyrazine, molecular formula is C4H6N4, 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.

Synthesis of (Z)-3-(3-(4-chloro-3,5-bis(trifluoromethyl)phenyl)-lH-l ,2,4-triazol-l- yl)-N’-(pyrazin-2-yl)acrylohydrazide: In a 50-mL, 3-necked, round-bottomed flask charged with a solution of (Z)-3-(3-(4- chloro-3,5-bis(trifluoromethyl)phenyl)-lH-l,2,4-triazol-l-yl)acrylic acid (0.8 g) in 1 : 1 EtOAc:THF (20 mL). The solution was cooled to -70 C and treated sequentially with 2- hydrazinopyrazine (0.275 g, 1.2 eq.), T3P (50% in EtOAc; 2.5 mL, 2.0 eq.) and DIPEA (1.44 mL, 4.0 eq.), added dropwise. The clear reaction mixture was stirred at -60C for 1 h before being concentrated under reduced pressure (25 C, 20 mm Hg) to afford crude compound. Purification by column chromatography using (60/120 mesh Si02, elution with 3-4% MeOH in CH2C12) afforded 0.30 g (yield: 30%) (Z)-3-(3-(4-chloro-3,5-bis(trifluoromethyl)phenyl)- lH-l ,2,4-triazol-l-yl)-N’-(pyrazin-2-yl)acrylohydrazide. 1H NMR (400 MHz, DMSO-d6) delta = 10.53 (s, 1H), 9.58 (s, 1H), 9.11 (s, 1H), 8.47 (s, 1H), 8.32 (s, 1H), 8.13 (s, 1H), 8.06 (s, 1H), 7.97 (s, 1H), 7.52-7.55 (d, J = 10.4 Hz, 1H), 6.08-6.1 1 (d, J = 10.4 Hz, 1H); LCMS for CnHnClFe yO [M+H]+ 478.76 found 478.1 (RT 2.64 min, purity: 100%).

The synthetic route of 54608-52-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KARYOPHARM THERAPEUTICS, INC.; SANDANAYAKA, Vincent, P.; SHACHAM, Sharon; MCCAULEY, Dilara; SHECHTER, Sharon; WO2013/19548; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

875781-43-4, 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 875781-43-4 as follows.

Step 4: Synthesis of 2-Bromo-7-iodo-5H-pyrrolo[2,3-b]pyrazine.[0285] To a solution of 2-Bromo-5H-pyrrolo[2,3-b]pyrazine (258 mg, 1.3 mmol) inacetone (5 ml) was added Af-iodosuccinimide (324 mg, 1.44 mmol) in one portion. Thereaction mixture was stirred at room temperature for 45 minutes. The resulting precipitatewas filtered off, washed with a minimal amount of acetone, and dried in vacuum to give thetitle compound as a light brown solid ^-NMR (500 MHz, d6-DMSO) £12.81 (s br, 1H),8.40 (s, 1H), 8.19 (d, 3.0Hz, 1H). MS: m/z 323.8/325.8 [MH+].

According to the analysis of related databases, 875781-43-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SGX PHARMACEUTICALS, INC.; WO2006/15124; (2006); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem