Pyrazines

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. 71257-38-0, name is 1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrazine, A new synthetic method of this compound is introduced below., category: Pyrazines

Diisopropylethylamine (12.15 mmole) and di-tert-butyl dicarbonate (8.9 mmole) were added to a solution of the correspondingly 1-substituted 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine (8.1 mmole) in DCM. The reaction mixture was stirred for 16 hours at 25 C. The organic phase was then washed with sodium carbonate solution, water and satd. NaCl solution, dried over Na2SO4 and concentrated by evaporation. The crude product was purified by column chromatography (silica gel, ethyl acetate/DCM, 99:1); 1,2,3,4-Tetrahydro-pyrrolo[1,2-a]pyrazine was dissolved in dichloromethane (90 ml) at to it DIPEA (12.15 mmol) and boc anhydride (8.9 mmol) were added at 0 C. The resulting reaction mixture was allowed to stir for 16 hrs at 25 C. Organic layer was washed with sodium carbonate, water and brine and finally dried over sodium sulfate. Evaporation of the organic layer gave the crude product which was purified by column chromatography (1% ethyl acetate in dichloromethane) or (10% ethyl acetate in hexane); 1,2,3,4-Tetrahydro-pyrrolo[1,2-a]pyrazine which was dissolved in dichloromethane (90 ml) at to it DIPEA (12.15 mmol) and boc anhydride (8.9 mmol) were added at 0 C. The resulting reaction mixture was allowed to stir for 16 hrs at 25 C. Organic layer was washed with sodium carbonate, water and brine and finally dried over sodium sulfate. Evaporation of the organic layer gave the crude product which was purified by column chromatography (1% ethyl acetate in dichloromethane) or (10% ethyl acetate in hexane).

The synthetic route of 71257-38-0 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

Reference of 939412-86-9, 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. 939412-86-9 name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, 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.

HATU (15.91 g, 41.8 mmol) was added to a stirred, cooled 0 C mixture of (6R,8aS)-3-oxooctahydroindolizine-6-carboxylic acid (7.3 g, 39.8 mmol), (3- chloropyrazin-2-yl)methanamine hydrochloride (7.89 g, 43.8 mmol) and DIPEA (10.44 ml, 59.8 mmol) in CH2C12 (25 ml) and the mixture was stirred at room temperature for 1 h. and then concentrated. The residue was purified by column chromatography on silica gel (Isco 240 g silica gel), eluting with CH2Cl2/MeOH (50/1) to give (6R,8aS)-N- ((3-chloropyrazin-2-yl)methyl)-3-oxooctahydroindolizine -6-carboxamide (11.15g, 36.1 mmol, 91 % yield) as a white solid. LC-MS: Ret. time 1.09 min; m/z 309.11 (M+H)+; 1HNMR (CDCI3, 500 Hz): 8.38 (1H, d, J = 2 Hz), 8.25 (1H, d, J = 2 Hz), 7.37 (1H, dd, J = 4 and 4.5 Hz), 4.56-4.72 (2H, m,l), 4.29 (1H, dd, J = 13 and 4.5 Hz),3.42-3.47 (m,l), 2.81 (1H, t, J = 13 Hz), 2.35 (2H, t, J = 8 Hz), 2.17-2.23 (1H, m), 2.04 (1H, d, J = 13.5 Hz), 1.94-1.96 (1H, m), 1.74-1.82 (1H, m), 1.55-1.62 (1H, m), 1.16-1.24 (1H, m).

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; MERCK SHARP & DOHME CORP.; WU, Hao; KIM, Ronald M.; LIU, Jian; GAO, Xiaolei; BOGA, Sobhana Babu; GUIADEEN, Deodialsingh; KOZLOWSKI, Joseph; YU, Wensheng; ANAND, Rajan; YU, Younong; SELYUTIN, Oleg B.; GAO, Ying-Duo; LIU, Shilan; YANG, Chundao; WANG, Hongjian; WO2014/114185; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 87486-34-8, A common heterocyclic compound, 87486-34-8, name is 3,5-Dibromo-1-methylpyrazin-2(1H)-one, molecular formula is C5H4Br2N2O, 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.

Example 17 A solution of the aminopyrazole (0.28 g, 2.5 mmol) and the dibromopyrazinone (0.74 g, 1.1 equiv) were heated to 120° C. in isopropanol for 1 h. The reaction mixture was cooled to RT, and the product was isolated by filtration (0.43 g, 57percent).

The synthetic route of 87486-34-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Roche Palo Alto LLC; US2010/4231; (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. 109-08-0, name is 2-Methylpyrazine, A new synthetic method of this compound is introduced below., SDS of cas: 109-08-0

General procedure: A 25 mL Schlenk tube equipped with a magneticstirring bar was charged with2,6-lutidine (0.75 mmol, 3equiv.), p-nitro-benzaldehyde(0.25 mmol), dioxane/water(1:1, 1ml) and [Hmim][H2PO4](1equiv.).The tube was sealed and heated at 100 for 24h. Aftercompletion of the reaction, the resulting solution was extracted with ether (3×10 ml). The organic layer was dried with anhydrous Na2SO4,and concentrated under vacuum. The residue was chromatographed on a silica gelcolumn eluted with a mixture of petroleum ether and ethyl acetate (1:1) to givepure products (92percent).

The synthetic route of 109-08-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Zhang, Xue-Yan; Dong, Dao-Qing; Yue, Tao; Hao, Shuang-Hong; Wang, Zu-Li; Tetrahedron Letters; vol. 55; 40; (2014); p. 5462 – 5464;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 1379338-74-5, These common heterocyclic compound, 1379338-74-5, name is 5,7-Dichloropyrido[3,4-b]pyrazine, 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.

Intermediate 18: 1,1-Dimethylethyl (3S)-3-{r(7-chloropyridor3,4-6lpyrazin-5- yl)oxy1methyl)-1-piperidinecarboxylate; 1 , 1-Dimethylethyl (3S)-3-(hydroxymethyl)-1-piperidinecarboxylate (129mg, 0.600mmol) (Apollo Scientific Limited) was taken up in N,N-dimethylformamide (DMF) (3ml), treated with sodium hydride (23.99mg, 0.600mmol) and allowed to stir at room temperature for 20min, a yellow solution resulted. 5,7-dichloropyrido[3,4- £>]pyrazine (100mg, 0.500mmol) was added and the reaction was allowed to stir at room temperature for a further 1 h. The reaction was partitioned between EtOAc (50ml) and NH4CI (50ml). The organic layer was dried using a hydrophobic frit and concentrated to give a brown oil. This oil was purified on silica (25g) using a 0-40% EtOAc/cyclohexane gradient. The appropriate fractions were summed and concentrated to give the title compound as a yellow gum (91 mg).LCMS (Method B): Rt = 1.26min, MH+ = 378.88

Statistics shows that 5,7-Dichloropyrido[3,4-b]pyrazine is playing an increasingly important role. we look forward to future research findings about 1379338-74-5.

Reference:
Patent; GLAXO GROUP LIMITED; ATKINSON, Francis Louis; ATKINSON, Stephen John; BARKER, Michael David; DOUAULT, Clement; GARTON, Neil Stuart; LIDDLE, John; PATEL, Vipulkumar Kantibhai; PRESTON, Alexander G; SHIPLEY, Tracy Jane; WILSON, David Matthew; WATSON, Robert J; WO2012/123312; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 369638-68-6,Some common heterocyclic compound, 369638-68-6, name is tert-Butyl (5-methylpyrazin-2-yl)carbamate, molecular formula is C10H15N3O2, 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.

A. 5-methylpyrazin-2-amine; To a solution tert-butyl 5-methylpyrazin-2-ylcarbamate (1.5 g, 7.17 mmol) in CH2CI2 (20 ml) was added TFA (2.6 mL, 35.86 mmol). The reaction mixture was stirred for 4 hours at room temperature after which, it was concentrated under reduced pressure. The reaction mixture was diluted with CH2CI2 and neutralized with sai.NaHCOs solution. The organic layer was separated and the aqueous layer was extracted with CH2CI2. The combined organic extracts were washed with brine, dried over MgS04, celite filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography using (30% to 50% Ethyl acetate/Hexane) as a solvent to afford title compound (580 mg, 74% yield). MS m/z : 110 [M+l] .

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route tert-Butyl (5-methylpyrazin-2-yl)carbamate, its application will become more common.

Reference:
Patent; DANA-FARBER CANCER INSTITUTE, INC.; GRAY, Nathanael, S.; WO2011/90738; (2011); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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