Category: 6966-01-4

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

Application of 6966-01-4,Some common heterocyclic compound, 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, molecular formula is C6H6BrN3O2, 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 8-iv) Methyl 3-amino-6-bromopyrazine-2-carboxylate (700 mg, 3 mmol) was dissolved in dioxane (4 mL) with 3-furan boronic acid (0.36 g, 3.2 mmol), potassium acetate (980 mg 10 mmol) and tetrakispalladium triphenylphosphine (200 mg, 0.17 mmol) in a microwave vessel. Nitrogen was bubbled through for 5 minutes, followed by sealing the vessel and microirradiating the mixture for 20 minutes at 170 0C. The reaction mixture was diluted with ethyl acetate/saturated sodium bicarbonate, dried over sodium sulfate, and concentrated to give a solid, which was purified by silica gel column chromatography (0 to 70 % EtOAc/hexanes) to give methyl 3-amino-6-(furan-3- yl)pyrazine-2-carboxylate as a solid. This methyl ester was dissolved in THF/MeOH and an aqueous solution of LiOH hydrate (150 mg, 3.6 mmol) was added. The reaction mixture was stirred for 1 hour at room temperature, concentrated to half the volume, and diluted with ethyl acetate/10% aqueous citric acid solution. The organic layer was washed with brine, dried, and concentrated in vacuo to yield 3-amino-6-(furan-3-yl)pyrazine-2- carboxylic acid as a solid (0.46 g, 2.3 mmol, 77 % overall yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-amino-6-bromopyrazine-2-carboxylate, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2008/36272; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, 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. Formula: C6H6BrN3O2

Step 1 : 3-amino-6-bromo-N-methylpyrazine-2-carboxamide[00261] Methyl 3-amino-6-bromo-pyrazine-2-carboxylate (7.5 g, 32.32 mmol) was suspended in 40% aqueous methylamine and the resulting mixture stirred vigorously at RT for 4 hours. The resultant precipitate was collected, washed with water and dried to give the desired product(6.73g, 90% Yield). IH NMR (400.0MHz, DMSO) d 2.76 (s, 3H), 7.75 (br s, 2H), 8.34 (s, IH),8.58 (b rs, IH) ppm; MS (ES+) 232.

The synthetic route of 6966-01-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-damien; DURRANT, Steven; KAY, David; O’DONNELL, Michael; KNEGTEL, Ronald; MACCORMICK, Somhairle; PINDER, Joanne; VIRANI, Anisa; YOUNG, Stephen; BINCH, Hayley; CLEVELAND, Thomas; FANNING, Lev, T.d.; HURLEY, Dennis; JOSHI, Pramod; SHETH, Urvi; SILINA, Alina; WO2010/54398; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 6966-01-4,Some common heterocyclic compound, 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, molecular formula is C6H6BrN3O2, 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.

Hydrazine hydrate (24 mL, 0.48 mol) was added dropwise to a stirred mixture of methyl 3-amino-6-bromopyrazine-2-carboxylate 29 (100 g, 0.42 mol) in EtOH (2 L). The mixture was heated at 50 C under nitrogen. The resulting thick suspension was stirred at 50 C for 16 h. Further hydrazine hydrate (2.5 mL) was added in one portion and the suspension was stirred at 50 C for a further 24 h. EtOH (500 mL) was charged to the thick reaction mixture and the mixture was allowed to cool to room temperature. The resulting suspension was filtered and the solid washed with ethanol (1 L) and dried in vacuo to give 3-amino-6-bromopyrazine-2-carbohydrazide (98 g, quantitative) as a cream solid. Pivalic anhydride (165 mL, 815 mmol) was added to a stirred mixture of 3-amino-6-bromopyrazine-2-carbohydrazide (172 g, 741 mmol) in acetonitrile (1.8 L) and the mixture was heated at 80 C for 1 h. The reaction was left to stir for 16 h. The required yellow solid material was isolated by filtration. The filtrate was partitioned between EtOAc (2 L) and aqueous sodium bicarbonate (2 L). The organic layer was washed with saturated brine and dried over MgSO4. The solution was filtered and concentrated to give an orange sticky solid which was triturated with MTBE (250 mL). The insoluble yellow solid was isolated by filtration. The combined solids were dried in vacuum at 50 C for 3 days to afford 3-amino-6-bromo-N’-pivaloylpyrazine-2-carbohydrazide (224 g, 96%) as a yellow solid. p-Toluenesulfonyl chloride (164 g, 862 mmol) was added portionwise to a suspension of 3-amino-6-bromo-N’-pivaloylpyrazine-2-carbohydrazide (227 g, 718 mmol) and DIPEA (300 mL, 1.8 mol) in acetonitrile (2.2 L). The mixture was stirred for 2 h at 70 C. The reaction was left to cool to room temperature overnight. The reaction mixture was partitioned between ethylacetate (2 L) and aq. sodium bicarbonate (2 L). The organic layer was washed with brine, dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting brown/beige solid was triturated with hot MTBE (1 L), isolated by filtration and dried to afford 5-bromo-3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine 30 as a yellow solid (187 g, 87%). The mother liquors were evaporated to dryness. The crude solid was triturated with MTBE (500 mL), filtered and washed with 100 mL of MTBE. The resulting solid was air dried overnight to afford a second crop of 5-bromo-3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine 30 (36 g, 17%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-amino-6-bromopyrazine-2-carboxylate, its application will become more common.

Reference:
Article; Barlaam, Bernard; Cosulich, Sabina; Delouvrie, Benedicte; Ellston, Rebecca; Fitzek, Martina; Germain, Herve; Green, Stephen; Hancox, Urs; Harris, Craig S.; Hudson, Kevin; Lambert-Van Der Brempt, Christine; Lebraud, Honorine; Magnien, Francoise; Lamorlette, Maryannick; Le Griffon, Antoine; Morgentin, Remy; Ouvry, Gilles; Page, Ken; Pasquet, Georges; Polanska, Urszula; Ruston, Linette; Saleh, Twana; Vautier, Michel; Ward, Lara; Bioorganic and Medicinal Chemistry Letters; vol. 25; 22; (2015); p. 5155 – 5162;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 6966-01-4,Some common heterocyclic compound, 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, molecular formula is C6H6BrN3O2, 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.

0.15 eq. palladium (II) acetate and 0.2 eq. 1,1′-bis(diphenylphosphino)-ferrocene were combined in dimethylformamide under nitrogen and heated to 50 C. for 20 minutes. R3 and n are each as defined herein. The reaction was allowed to cool to room temperature and 1.0 eq. of the pyrazine, 1.5 eq. of the boronic acid and 1.15 eq. of triethylamine were added. The reaction was heated to 90 for 12 hours and allowed to cool to room temperature. The DMF was removed by rotary evaporation. The crude reaction mixture was dissolved in chloroform and washed twice with 1N aq. HCl and then twice with saturated aq. NaHCO3 solution. The organic layer was dried over sodium sulfate, filtered and concentrated. Material was purified by silica gel chromatography using 100% chloroform as eluent.

The synthetic route of 6966-01-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Pfizer Inc; US2004/180905; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 6966-01-4, 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. 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

A mixture of palladium (II) acetate (145 mg, 0.65 mmol) and 1,1′-bis(diphenylphosphino)-ferrocene (493 mg, 0.86 mmol) in DMF (70 ml) was stirred at 50 C. for 15 minutes and cooled to r.t. The mixture was evacuated and vented with argon. 3-Amino-6-bromopyrazine-2-carboxylic acid methyl ester (5.0 g, 21.5 mmol), furan-3-yl-boronic acid (2.79 g, 23.7 mmol) and triethylamine (4.51 ml, 32.3 mmol) were added and the reaction mixture was stirred at 90 C. for 16 h. The solvent was evaporated and the product was obtained after purification by silica gel chromatography using a heptane /ethyl acetate gradient as yellow solid (2.92 g, 61.8%). MS: M=220.2 (M+H)+

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, Methyl 3-amino-6-bromopyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Bleicher, Konrad; Flohr, Alexander; Groebke Zbinden, Katrin; Gruber, Felix; Koerner, Matthias; Kuhn, Bernd; Peters, Jens-Uwe; Sarmiento, Rosa Maria Rodriguez; US2011/306589; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 6966-01-4,Some common heterocyclic compound, 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, molecular formula is C6H6BrN3O2, 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 methyl 3-amino-6-bromopyrazine-2-carboxylate (100 mg, 0.43 mmol) in MeOH (5 mL) was added 2 mL of NaOH aqueous solution (5 N). After being stirred at 50C for 4 h, the mixture was cooled and acidified with 1 M HCl to a pH of 2. The precipitate was collected by filtration and washed with water to afford the product of 3-amino-6- bromopyrazine-2-carboxylic acid (90 mg, yield: 96%). XH-NMR (DMSO-ifc, 400 MHz) delta 8.38 (s, 1H), 7.51-7.56 (m, 2H). MS (M+H)+: 218 / 220.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-amino-6-bromopyrazine-2-carboxylate, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; DAI, Xing; LIU, Hong; PALANI, Anandan; HE, Shuwen; NARGUND, Ravi; XIAO, Dong; ZORN, Nicolas; DANG, Qun; MCCOMAS, Casey, C.; PENG, Xuanjia; LI, Peng; SOLL, Richard; WO2014/209727; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 6966-01-4, The chemical industry reduces the impact on the environment during synthesis 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, I believe this compound will play a more active role in future production and life.

Preparation 9. Synthesis of 3-amino-6-bromopyrazine-2-carbohydrazide[00222] Step 1 : To a suspension of methyl 3-amino-6-bromo-pyrazine-2-carboxylate (2.5 g, 10.8 mmol) in ethanol (50 mL) was added hydrazine hydrate (3.2 g, 3 mL, 64.6 mmol) and the reaction mixture heated at 70 C for 1.5 hours forming a thick yellow solid. The reaction mixture was filtered and the solid washed with water (20 mL) and ethanol (40 mL). The solid was dried in vacuo to yield 3-amino-6-bromo-pyrazine-2-carbohydrazide (2.7 g, 94% yield) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) delta 4.53 (d, J = 3.5 Hz, 2H), 7.62 (s, 2H), 8.31 (s, 1H) and 9.78 (s, 1H) ppm; LC/MS m/z 233.1 [M+H]+

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, Methyl 3-amino-6-bromopyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-Damien; MACCORMICK, Somhairle; STORCK, Pierre-Henri; PINDER, Joanne; O’DONNELL, Michael, Edward; KNEGTEL, Ronald Marcellus, Alphonsus; YOUNG, Stephen, Clinton Young; KAY, David; REAPER, Philip, Michael; DURRANT, Steven, John; TWIN, Heather, Clare; DAVIS, Christopher, John; WO2012/138938; (2012); 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. 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., category: Pyrazines

Step 2; A suspension of compound 2 (28.5 g, 120 mmol) in an aqueous solution of 48% HBr (120 mL) and acetic acid (30 mL) was cooled to 0 C., and then treated with a solution of bromine (18 mL, 336 mmol) in acetic acid (18 mL) over a period of 45 min. A solution of NaNO2 (8.28 g, 420 mmol) in water (15 ml) was added while maintaining the temperature at 0 C., stirring was continued for further 30 min. After completion of reaction (reaction progress was monitored by TLC), the excess bromine was quenched by the drop wise addition of 30% aqueous solution of NaHSO3 (180 mL). The resulting precipitate was filtered and purified by column chromatography on silica gel eluted with 10% ethyl acetate in hexane to afford compound 3 as a white crystalline solid (18 g, 49%). MS m/z (ES): 294 (M+H)+.

The synthetic route of 6966-01-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; de Vicente Fidalgo, Javier; Hermann, Johannes Cornelius; Lemoine, Remy; Li, Hongju; Lovey, Allen John; Sjogren, Eric Brian; Soth, Michael; US2011/59118; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, 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 6966-01-4, Formula: C6H6BrN3O2

Step 2; A suspension of compound 2 (28.5 g, 120 mmol) in an aqueous solution of 48% HBr (120 mL) and acetic acid (30 mL) was cooled to 0 C., and then treated with a solution of bromine (18 mL, 336 mmol) in acetic acid (18 mL) over a period of 45 min. A solution of NaNO2 (8.28 g, 420 mmol) in water (15 ml) was added while maintaining the temperature at 0 C., stirring was continued for further 30 min. After completion of reaction (reaction progress was monitored by TLC), the excess bromine was quenched by the drop wise addition of 30% aqueous solution of NaHSO3 (180 mL). The resulting precipitate was filtered and purified by column chromatography on silica gel eluted with 10% ethyl acetate in hexane to afford compound 3 as a white crystalline solid (18 g, 49%). MS m/z (ES): 294 (M+H)+.

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, Methyl 3-amino-6-bromopyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; de Vicente Fidalgo, Javier; Hermann, Johannes Cornelius; Lemoine, Remy; Li, Hongju; Lovey, Allen John; Sjogren, Eric Brian; Soth, Michael; US2011/59118; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem