Category: 6966-01-4

Reference 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,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.

Pd(dppf)CI2 (158 mg, 0.215 mmol) was added to a suspension of methyl 3-amino-6- bromopyrazine-2-carboxylate (1.00 g, 4.31 mmol), ethylboronic acid (0.637 g, 8.62 mmol) and K2CO3 (1.79 g, 12.9 mmol) in DME (20 ml). The resultant suspension was de-gassed by bubbling a stream of nitrogen through the reaction mixture for 1 min. The reaction mixture was heated at 90 C for 17 h then allowed to cool to RT. The reaction was recharged with ethylboronic acid (318 mg, 4.31 mmol) and Pd(dppf)Cl2 (79 mg, 0.11 mmol) then heated at 90 C for 2 h. The reaction mixture was allowed to cool to RT then added to saturated aq. NaHC03 solution (40 ml). The resultant mixture was extracted with EtOAc (2×40 ml) then the combined organic extracts were washed with brine (40 ml), dried over MgS0 , filtered and concentrated in vacuo. The crude material was purified by flash column chromatography on a silica column (50 g). The column was eluted with EtOAc: heptane, increasing the gradient linearly from 6:94 to 50:50 over 10 column volumes. The desired fractions were combined and evaporated to yield the product as a yellow solid (322 mg, 41 %).1H NMR (250 MHz, CDCl3 ) delta 8.14 (s, 1 H), 6.27 (s, 2H), 3.98 (s, 3H), 2.79 (q, J = 7.6 Hz, 2H), 1.29 (t, J = 7.6 Hz, 3H).LC/MS (System A): m/z (ESI+) = 182 [MH+], Rt = 0.81 min, UV purity = 100%.

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; ENTERPRISE THERAPEUTICS LIMITED; MCCARTHY, Clive; HARGRAVE, Jonathan David; HAY, Duncan Alexander; SCHOFIELD, Thomas Beauregard; WENT, Naomi; (111 pag.)WO2017/221008; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. SDS of cas: 6966-01-4

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

Reference 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

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. 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Formula: C6H6BrN3O2

Methyl 3-amino-6-bromopyrazine-2-carboxylate (10 g,1 eq) was suspended in concentrated H2SO4 (40 mL), andthen, NaNO2 (5.96 g, 2 eq) was added in batches at -5 to0 C, after which the reaction was stirred at 25 C for 2 huntil the solid was all dissolved. Then, the reaction solutionwas poured into ice water (400 mL) and vigorously stirredfor 1.5 h. Afterward, the solution was extracted with ethylacetate (3 9 50 mL). The organic layer was combined andwashed with water (3 9 30 mL). Then, it was dried withanhydrous Na2SO4 for 5 h and filtered to remove the dryingagent. The ethyl acetate was removed by distillation under reduced pressure to obtain methyl 3-hydroxy-6-bromopyrazine-2-carboxylate (9.3 g, 92.7%) (TLC,EA:MeOH = 1:1, v/v, Rf = 0.77).Methyl 3-hydroxy-6-bromopyrazine-2-carboxylate(4)Yield: 92.7%, gray solid, m.p.: 120-122 C (Lit.120.5-121.5 C) (Caldwell et al. 2012). 1H-NMR(400 MHz, DMSO-d6): d 8.40 (s, 1H), 3.85 (s, 3H). 13CNMR(101 MHz, DMSO-d6): d 163.20, 157.11, 143.89,134.81, 122.06, 52.43. MS (EI): m/z = 233.0 (M?, Br79,40), 235.0 (M?, Br81, 40), 202.0 (M?, -OCH3, Br79, 45),204.0 (M?, -OCH3, Br81, 25), 174.0 (M?, -COOCH3,Br79, 100), 176.0 (M?, -COOCH3, Br79, 60).

According to the analysis of related databases, 6966-01-4, the application of this compound in the production field has become more and more popular.

Reference:
Article; Liu, Feng-Liang; Li, Cui-Qin; Xiang, Hao-Yue; Feng, Si; Chemical Papers; vol. 71; 11; (2017); p. 2153 – 2158;,
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 6966-01-4 as follows. category: Pyrazines

The compound 3-amino-6-bromopyrazine-2-carboxylic acid methyl ester 3a (20.0 g, 86.2 mmol) was added to a 500 mL three-necked flask, dioxane (40mL), HBr (200mL) and acetic acid (40mL), stirred and dissolved -5 C dropwise to the reaction system was added NaNO2 (19.6g, 285mmol), the solution was stirred at -5 C (20mL) acetic acid for 4 hours. The system was poured into a solution of Na2SO3 and extracted with ethyl acetate. The organic phase was washed with water, brine, dried over anhydrous sodium sulfate, and dried under reduced pressure using a rotary evaporator, purified by column to give the title compound 3b (12.0g, 40.8mmol), in a yield of 47.3%

According to the analysis of related databases, 6966-01-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Shanghai Huahuituo Pharmaceutical Technology Co., Ltd.; Zhejiang Huahai Pharmaceutical Co., Ltd.; Xu Xin; Zhang Tian; Li Yunfei; Wang Guan; Zhu Weibo; Li Qiang; Qu Minkai; Zhang Linli; Song Jinqian; Liu Lei; Chen Haiji; Liu Qiang; Wang Yijin; Ge Jian; (67 pag.)CN109535164; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 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.

(iv) 3-Amino-6-bromopyrazine-2-carboxylic acid: To a solution of the product of step (iii) (200 g, 0.86 mol) in MeOH (500 mL) was added 5 N-NaOH (500 mL) slowly. The resulting mixture was stirred at 50 C for 3 hours. MeOH was removed under a reduced pressure and water (300 mL) added to the reaction mixture. The solution was acidified to pH 3 with 6N-HC1. The solution was extracted with EtOAc and washed with water. The combined organic extract was dried over Na2S04, filtered and evaporated to dryness to afford the subtitle compound (iv) as a brown yellow solid (180 g). 1H-NMR (400 MHz, CDC13) delta 8.30 (s, 1H);HPLC Retention Time = 0.850min.

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; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; FENG, Tao; SANGANEE, Hitesh, Jayantilal; WADA, Hiroki; WO2011/89416; (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, Recommanded Product: Methyl 3-amino-6-bromopyrazine-2-carboxylate

(4-(5-(5-Amino-6-(5-tert-butyl- 1 ,3,4-oxadiazol-2-yl)pyrazin-2-yl)- 1 -methyl- 1H- 1 ,2,4- triazol-3 -yl)piperidin- 1 -yl)-3 -(tetrahydro-2H-pyran-2-yloxy)propan- 1 -one (Example 2.1) was prepared as follows: Hydrazine hydrate (23.59 mL, 480.75 mmol) was added dropwise to a stirred mixture of methyl 3-amino-6-bromopyrazine-2-carboxylate (100 g, 418.04 mmol) in EtOH (2 L). The mixture was heated at 50C under nitrogen. The resulting thick suspension was stirred at 50 C for 16 hours. Further hydrazine (2.5 mL) was added in one portion and the suspension was stirred at 50 C for a further 24 hours. Ethanol (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: 1H NMR Spectrum: (DMSO-d6) 4.52 (2H, s), 7.59 (2H, s), 8.30 (1H, s), 9.74 (1H, s); Mass Spectrum [M+H]+ = 232.

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; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BARLAAM, Bernard Christophe; BERRY, David; DELOUVRIE, Benedicte; HARRIS, Craig Steven; LAMBERT-VAN DER BREMPT, Christine Marie Paul; OUVRY, Gilles; REID, Gary Patrick; TOMKINSON, Gary Peter; WO2014/114928; (2014); 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., HPLC of Formula: C6H6BrN3O2

To a solution of 3-amino-6-bromo-pyrazine-2-carboxylic acid methyl ester (3g, 12.9 mmol) in DMF (40ml) was added 3-(hydroxymethyl)benzoic acid (2.16g, 14.22 mmol) followed by Et3N (2.7ml, 19.39 mmol) under nitrogen at room temperature. The mixture was stirred for 10 min before adding 1 ,1′-bis[dit- butylphosphino)ferrocene]paliadium chloride (0.25g, 0.039 mmol) and stirred overnight at 900C. The cooled reaction mixture was condensed. The residue dissolved in THF-EtOAc mixture (200ml, 1 :1), filtered to remove catalyst and evaporated. The filtrated was washed with brine, dried (MgSO4) and condensed. The resultant brown solid residue was subjected to flash column chromatography on silica eluting gradient of hexane to (3:1 , v/v) ethyl acetate and hexane to give title compound (1.61g, 48%) as a yellow/orange solid; LC/MS: Rt 1.74 (Method A) [M+H]+ 260.

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

Reference:
Patent; VERNALIS (R & D) LIMITED; WO2008/38010; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 6966-01-4, These common heterocyclic compound, 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-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.

Preparation of methyl 3,6-dibromopyrazine-2-carboxylate A mixture of 3 – amino – 6 – bromopyrazine – 2 – carboxylic acid methyl ester (4 ? 6 2 g ’20 mmol), aqueous hydrobromic acid (48%, 24 ml) and acetic acid (3.2 ml) was added to the reactor, -5 C. The solution (20 ml) of the solution of acetic acid (5 ml) and sodium nitrite (4.8 g, 70 ml) was slowly added successively -5 C stirring reaction lh. The reaction was terminated, washed with saturated sodium sulfite solution, extracted with ethyl acetate and water, washed with saturated NaCl solution and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound as an off-white solid.

Statistics shows that Methyl 3-amino-6-bromopyrazine-2-carboxylate is playing an increasingly important role. we look forward to future research findings about 6966-01-4.

Reference:
Patent; NANJING SHENGHE PHARMACEUTICAL CO., LTD.; WANG, YONG; ZHAO, LIWEN; LIU, YANG; ZHANG, JINGZHONG; WANG, DEZHONG; GAO, YIPING; CHEN, HONGYAN; ZHANG, CANG; ZHANG, DI; (68 pag.)TWI523856; (2016); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem