Category: Pyrazines

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. 63286-28-2, name is 2-Chloro-3-hydrazinylpyrazine, This compound has unique chemical properties. The synthetic route is as follows., Safety of 2-Chloro-3-hydrazinylpyrazine

Into a 500-mL 3 -necked round-bottom flask, was added 2-chloro-3- hydrazinylpyrazine (5.0 g, 34.59 mmol, 1.00 equiv) in tetrahydrofuran (100 mL). While stirring this solution at 0 C a solution of TFAA (8.0 g, 38.09 mmol, 1.10 equiv) in tetrahydrofuran (100 mL) was added dropwise. The resulting solution was stirred for 1 h and then washed with sodium chloride(aq). The resulting solution was extracted with ethyl acetate and the organic layers were combined and concentrated under vacuum. Purification by flash chromatography (silica gel column with ethyl acetate: petroleum ether (1:5)) provided 7.3 g (88%) of 1-1 as a white solid.

According to the analysis of related databases, 63286-28-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; IDEAYA BIOSCIENCES, INC.; BECK, Hilary, Plake; GONZALEZ-LOPEZ, Marcos; SUTTON, James, Clifford, Jr.; (86 pag.)WO2019/156989; (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. 13484-56-5, name is 3-Chloro-6-methoxypyrazin-2-amine, A new synthetic method of this compound is introduced below., Formula: C5H6ClN3O

To a solution of 3.15 g of 3-chloro-6-methoxypyrazin-2-amine in 20 mL of triethylamine, 2.6 mL of ethyl acrylate and 0.50 g of bis(tri-tert-butylphosphine)palladium(0) were added, and the mixture was stirred at an external temperature of 120 to 130C for 2 hours in a sealed tube. Thereto was further added 5 mL of triethylamine, and the mixture was stirred at the same temperature for 4 hours 50 minutes. The reaction mixture was cooled to room temperature and left overnight, then 0.5 mL of ethyl acrylate and 0.25 g of bis(tri-tert-butylphosphine)palladium(0) were added thereto and the mixture was stirred at an external temperature of 115 to 125C for 9 hours 20 minutes in a sealed tube. The reaction mixture was cooled to room temperature, water and ethyl acetate were then added thereto, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography using an eluent of hexane:ethyl acetate = 4:1 to obtain 2.55 g of ethyl (2E)-3-(3-amino-5-methoxypyrazin-2-yl)acrylate as a yellow solid. 1H-NMR (CDCl3) delta: 1.32 (3H, t, J = 7.1 Hz), 3.91 (3H, s), 4.26 (2H, q, J = 7.1 Hz), 4.72 (2H, s), 6.73 (1H, d, J = 15.1 Hz), 7.61-7.68 (2H, m)

The synthetic route of 13484-56-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TOYAMA CHEMICAL CO., LTD.; Taisho Pharmaceutical Co. Ltd.; EP2022793; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 109-08-0, The chemical industry reduces the impact on the environment during synthesis 109-08-0, name is 2-Methylpyrazine, I believe this compound will play a more active role in future production and life.

A solution of lithium diisopropylamine [prepared from a solution of butyl lithium in hexanes (100 mL, 2.5M) and diispropylamine (25.3 g) at -35¡ã C.] was treated with a solution of 2-methylpyrazine (23.5 g) in dry tetrahydrofuran (300 mL) at -20¡ã C. The mixture was stirred at -20¡ã C. for 1 hour then cooled to -78¡ã C. and treated with a solution of allyl bromide (30.8 g) in dry tetrahydrofuran (300 mL). This mixture was warned to room temperature and stirred at this temperature for 2 hours then left overnight and then treated with saturated ammonium chloride solution (50 mL) followed by water (200 mL). The mixture was then extracted twice with ether (200 mL). The combined extracts were dried over magnesium sulfate then evaporated. The residue was distilled to give the title compound (22 g) as a colorless oil, b.p. 70¡ã C./1 mm Hg.

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-Methylpyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Cox, Paul J.; Majid, Tahir N.; Lai, Justine Y.Q.; Morley, Andrew D.; Amendola, Shelley; Deprets, Stephanie D.; Edlin, Christopher; US2004/9983; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 16298-03-6,Some common heterocyclic compound, 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, molecular formula is C6H7N3O2, 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 1 : 5-Amino-6-(6-methyl-lH-benzimidazol-2-yl)-N-(tetrahydrofuran-2- ylmethyl)pyrazine-2-carboxamide (Compound 11-52)SCHEME IMETHOD A:Step 1: Methyl 3-amino-6-bromopyrazine-2-carboxylate[00139] A mixture of methyl 3-aminopyrazine-2-carboxylate (8.35 g, 54.53 mmol) and N- bromo-succinimide (9.705 g, 54.53 mmol) was stirred in MeCN (100 mL) at ambient temperature overnight. The resultant precipitate was filtered, washed with MeCN and dried to give the desired product as a yellow solid (1 1.68 g, 92percent Yield)XH NMR (400.0 MHz, DMSO) delta 3.85 (s, 3H), 7.55 (br s, 2H) and 8.42 (s, 1H) ppm; MS (ES+) 233.0

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

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-Damien; DURRANT, Steven, John; KNEGTEL, Ronald, Marcellus, Alphonsus; O’DONNELL, Michael; REAPER, Philip, Michael; WO2011/143419; (2011); 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. 6294-70-8, name is 5,6-Dimethylpyrazin-2-amine, A new synthetic method of this compound is introduced below., Recommanded Product: 6294-70-8

At room temperature,Potassium tert-butoxide (5.60 g, 50 mmol)To a solution of 5,6-dimethylpyrazin-2-amine (1.23 g, 10 mmol)In 250 ml of dry THF.After stirring for 15 minutes,2-Nitrothiazole-4-carbonyl chloride (2.10 g, 11 mmol)In 50 ml of dry THF.The reaction mixture was stirred for 4 hours at room temperature,Then poured into saturated aqueous NaHCO 3 solution and extracted with EtOAc.The organic phase was washed with saturated aqueous NaCl solution,Dry over anhydrous Na2SO4 and concentrate to dryness.After purification by silica gel flash chromatography (cyclohexane / EtOAc: 90/10 to 50/50)Obtained as a white solid1.69 g of N- (5,6-dimethylpyrazin-2-yl) -2-nitrothiazole-4-amide(Yield: 61.0%).

The synthetic route of 6294-70-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Mudanjiang Medical School; Liu Shijuan; Hou Jiafu; Li Xuemei; Zhou Xue; Wu Yiyan; Zhao Cong; Tong Lei; Zhang Chaoli; Liu Jiawei; Cui Xinyu; (11 pag.)CN107056819; (2017); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 1320266-90-7,Some common heterocyclic compound, 1320266-90-7, name is 8-Chloro-3-isopropylimidazo[1,5-a]pyrazine, molecular formula is C9H10ClN3, 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 stirred solution of 8-chloro-3-isopropylimidazo[i,5-ajpyrazine (31 g, 158.5 mmol) indry THF (300 mL) at -78 C under nitrogen was added n-butyllithium (2.5 M in hexanes,82.4 mL, 206 mmol), keeping the internal temperature below -65 C. After stirring for 30 mma solution of iodine (56.3 g, 221.8 mmol) in THF (50 mL) was added dropwise over 10 mmkeeping the internal temperature below -65 C during addition. The resulting suspension wasstirred for 1 hour whilst warming to -10 C then the reaction mixture was quenched by theaddition of saturated aqueous NH4C1 and extracted with 2-methyltetrahydrofuran (x3). The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by passage through a silica-gel pad, eluting with 0-20% EtOAc in DCM to give an orange solid, which was triturated with Et20 to givethe title compound 5B as a yellow solid (41.2 g, 81%). LC-MS: Rt = 1.29 mm, m/z = 322.0[M+Hj +

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 8-Chloro-3-isopropylimidazo[1,5-a]pyrazine, its application will become more common.

Reference:
Patent; OPTIKIRA LLC; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; KEENAN, Richard M.; BACKES, Bradley J.; MALY, Dustin J.; REYNOLDS, Charles; WHITTAKER, Ben; KNIGHT, Jamie; SUTTON, Jon; HYND, George; PAPA, Feroz, R.; OAKES, Scott, A.; (147 pag.)WO2019/46711; (2019); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 914452-71-4, 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 914452-71-4 as follows.

To a solution of 2-chloro-4-phenoxypyrrolo[2,1-J][1,2,4]triazine (100 mg, 0.407 mmol), 2-bromo-6-methylpyrazine (70.4 mg, 0.407 mmol) and hexamethylditin (0.084mL, 0.407 mmol) in 1,4-dioxane (7 mL) was added tetrakis(triphenylphosphine)palladium(0) (47.0 mg, 0.041 mmol). The reaction mixture was degassed with argon and was stirred at 100 C for 18 h. The solvent was removed under reduced pressure to get a brown solid. The crude residue was purified by silica gel chromatography (ethyl acetate:Petroleum ether, 10/90) to obtain 2-(6-methylpyrazin-2-yl)-4-phenoxypyrrolo[2,1-J][1,2,4]triazine (85 mg, 0.280 mmol, 68.8 % yield). LCMS m/z 304.4 (M+H); rt 1.45 mm; Conditions B.

According to the analysis of related databases, 914452-71-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; HARIKRISHNAN, Lalgudi S.; FINK, Brian E.; BORZILLERI, Robert M.; TONUKUNURU, Gopikishan; RAHAMAN, Hasibur; WARRIER, Jayakumar Sankara; SESHADRI, Balaji; (411 pag.)WO2017/15425; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 221136-66-9, name is Ethyl 2-(3-bromo-6-methyl-2-oxopyrazin-1(2H)-yl)acetate, 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 221136-66-9, Recommanded Product: 221136-66-9

STEP A: r3-(2,2-Difluoro-2-phenyl-ethylamino)-6-methyl-2-oxo-2H-pyrazin- 1-yll-acetic acidA 4-neck round bottom flask, equipped with thermometer, and addition funnel, is charged with 3-bromo-6-methyl-2-oxo-2H-pyrazin-1-yl)-acetic acid ethyl ester (44.00 g, 160.0 mmol), anhydrous Na2HPO4 (31.8 g, 224 mmol), and n-butanol (210 g). 2,2-Difluoro-2-phenyl-ethylamine (30.15 g, 192 mmol) is then added in one portion. The resulting suspension is heated to reflux over 30 – 90 min and further stirred for 12 – 16 h. The suspension is cooled to 75- 9O0C over 30-60 min, and water (130 g) is added over 15-30 min, resulting in a clear 2-phasic reaction mixture. 30% NaOH(aq) ( 95.2 g, 714 mmol) is added and the reaction mixture is further stirred for 60 min at 75-850C. After completion of the hydrolysis, 32/34% HCI (aq) (85 g, 778 mmol) is added dropwise, resulting in the precipitation of the product. Complete precipitation is achieved by cooling the suspension to 0-100C and stirring at this temperature for additional 30 min. The product ([3-(2,2-Difluoro-2-phenyl-ethylamino)-6- methyl-2-oxo-2H-pyrazin-1 -yli-acetic acid) is centrifuged and washed with water (100 g) and then with a mixture of ethanol (40 g) and water (50 g). The isolated product is then vacuum dried at 40-600C.Note: Step A may alternatively be completed by reacting the 3-bromo-6- methyl-2-oxo-2H-pyrazin-1-yl)-acetic acid ethyl ester with the HCI salt of 2,2- difluoro-2-phenyl-ethylamine. In this case, an aqueous work-up with TBME and 30% NaOH(aq) is required to isolate the product.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 2-(3-bromo-6-methyl-2-oxopyrazin-1(2H)-yl)acetate, and friends who are interested can also refer to it.

Reference:
Patent; JANSSEN PHARMACEUTICA, N.V.; WO2007/146553; (2007); A2;,
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. 54013-07-9, name is 5-Methoxypyrazin-2-amine, A new synthetic method of this compound is introduced below., name: 5-Methoxypyrazin-2-amine

2-Amino-5-methoxypyrazine (1.5 g, 12.0 mmol; CASNo. 54013-07-9) was dissolved in anhydrous THF under nitrogen and cooled in a dry ice-acetone bath. To this solution was added pyridine (2.3 mL, 28.8 mmol). After 30 min phenyl chloroformate ( 1.7 mL, 13.2 mmol) was added dropwise. The reaction mixture was allowed to gradually warm to room temperature. After 2 hours ethyl acetate (90 mL) and water (45 mL) were added. The aqueous layer was back extracted once with ethyl acetate. The combined organic layers were washed twice with brine, then dried (MgSO4), filtered and concentrated. The residue was triturated with ether: ethyl acetate (50 mL: 2 mL). The solid was collected by vacuum filtration and washed with ether. To give the title compound as a pale yellow solid (2.5 g, 10.1 mmol, 85%) 1H NMR (400 MHz, DMSO-d6) delta ppm 10.79 (s, 1 H), 8.58 (s, 1 H), 8.13 (s, 1 H), 7.36-7.52 (m, 2H), 7.16-7.34 (m, 3H), 3.88 (s, 3H). m/z 246.1

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; PFIZER INC.; WO2009/127948; (2009); A1;,
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