Month: December 2020

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. Recommanded Product: 5,7-Dichloropyrido[3,4-b]pyrazine

Intermediate 5: 1,1-Dimethylethyl (3R)-3-{[(7-chloropyrido[3,4-b]pyrazin-5-yl)amino]methyl}-1-piperidinecarboxylate 5,7-dichloropyrido[3,4-b]pyrazine (1 g, 5.00 mmol) was taken up in N-Methyl-2-pyrrolidone (NMP) (10 ml) and treated with 1,1-dimethylethyl (3R)-3-(aminomethyl)-1-piperidinecarboxylate (1.179 g, 5.50 mmol) (Apollo Scientific Ltd) and diisopropylethylamine (1.310 ml, 7.50 mmol). The reaction was irradiated in a Biotage microwave at 130 C. for 30 min. The reaction was partitioned between EtOAc (100 ml) and water (100 ml). The organic layer was washed with brine (100 ml), dried using a hydrophobic frit and concentrated to give a black solid. This solid was purified on silica (50 g) and eluted with a 10-40% EtOAc/cyclohexane gradient. The appropriate fractions were combined and concentrated to give the title compound as a deep orange solid (1.542 g). LCMS (Method B): Rt=1.28 min, MH+=377.92

The synthetic route of 5,7-Dichloropyrido[3,4-b]pyrazine has been constantly updated, and we look forward to future research findings.

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.; US2014/5188; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 486424-37-7, A common heterocyclic compound, 486424-37-7, name is 3-Amino-6-bromopyrazine-2-carboxylic acid, molecular formula is C5H4BrN3O2, 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.

Triethyl amine (0.57 ML, 4.13 mmol) was added to a mixture of 3-AMINO-6-BROMO-2- pyrazinecarboxylic acid (0.30 g, 1.38 mmol; described in: Ellingson, R. C.; Henry, R. L. J. Am. Chem. Soc. 1949,2798-2800), 0- (BENZOTRIAZOL-1-YL)-NNN’, N’- tetramethyluroniumtetrafluoroborate (0.486 g, 1.51 mmol) and 1-hydroxybenzotriazole (0.204 g, 1.51 mmol) in N, N-DIMETHYLFORMAMIDE/ACETONITRILE, (1: 1,5 ML). After stirring for 0.5 h at room temperature, 2-(LH-PYRROL-L-YL)-L-ETANAMINE (0.182 g, 1.65 mmol) was added and the resulting mixture was stirred overnight at room temperature. Approximately, 10 ML water was added and a precipitation was formed. The precipitation was filtered and washed with water which gave 0.21 g (50% yield) of a light brown solid: MS (ESP) M/Z 310,312 (M++1). The solid (0.16 g, 0.516 mmol) from previous step was dissolved in tetrahydrofuran/water (5: 1,5 mL) together with [4- [ (4-methyl-l-piperazinyl) sulfonyl] phenyl] boronic acid (0.220 g, 0.77 mmol), sodium carbonate (0.164 g, 1.55 mmol) and Pd (dppf) CL2 (0.013 g, 1.5 nmmol). The resulting mixture was stirred at 70 C overnight (N2-atmosphere). The mixture was evaporated onto silica and purified on silica using toluene/acetonitrile, (1: 2 to 1: 4), as the eluent which afforded a yellow solid which was dried in vacuo at 40 C. The product was dissolved in a methylene chloride/methanol mixture, (9: 1), and hydrochloride acid in diethyl ether (0.28 mL, 1 M) was added. The precipitate was washed with diethyl ether and dried in vacuo to give 69 mg (23% yield) of the title compound : 1H NMR (DMSO-d6) 5 8.94 (s, 1 H), 8.90 (t, J = 6 Hz, 1 H), 8.43 (d, J = 8 Hz, 2 H), 7.82 (d, J = 8 Hz, 2 H), 6.79 (t, J = 2 HZ, 2 H), 6.01 (t, J = 2 HZ, 2 H), 4.12 (t, J = 7 Hz, 2 H), 3.83 (d, J = 12 Hz, 2 H), 3.63 (quart, J = 6 Hz, 2 H), 3.44 (d, J = 12 Hz, 2 H), 3.15 (m, 2 H), 2.73 (m, 5 H) ; 13C NMR (DMSO-d6) 8 165.8, 154.5, 144.8, 140.8, 135.9, 133.3, 127.9, 126.1, 124.6, 120.7, 107.8, 51.5, 47.6, 43.0, 41.8 ; MS (ESP) M/Z 470 (M++1).

The synthetic route of 486424-37-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; WO2004/55009; (2004); 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. 88625-24-5, name is 5-Chloropyrazine-2-carbaldehyde, A new synthetic method of this compound is introduced below., Safety of 5-Chloropyrazine-2-carbaldehyde

To a solution of 5-chloropyrazine-2-carbaldehyde (500 mg, 3.51 mmol) in CH2CI2 (10 mL) was added (diethylamino)difluorosulfonium tetrafluoroborate (2.0 g, 8.77 mmol) and triethylamine trihydrofluoride (0.57 mL, 3.51 mmol). The reaction mixture was stirred for 18 hours at ambient temperature. The reaction mixture was diluted with water and was extracted with CH2CI2. The organic layer was dried over anhydrous MgSO/t, filtered and concentrated under reduced pressure. Purification of the residue via column chromatography (Si(, heptane:ethyl acetate 0-65%) gave the title (200 mg, 1.22 mmol, 35% yield). JH NMR (500 MHz, DMSO- ) delta ppm 9.00 – 8.93 (m, 1H), 8.86 (q, J = 1.1 Hz, 1H), 7.17 (t, J = 54.0 Hz, 1H); MS (ESI+) m/z 186 (M+Na)+.

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; CALICO LIFE SCIENCES LLC; ABBVIE INC.; MARTIN, Kathleen, Ann; SIDRAUSKI, Carmela; FROST, Jennifer, M.; PLIUSHCHEV, Marina, A.; TONG, Yunsong; BLACK, Lawrence, A.; XU, Xiangdong; SHI, Lei; ZHANG, Qingwei, I.; CHUNG, Seungwon; SWEIS, Ramzi, Farah; DART, Michael, J.; RANDOLPH, John, T.; MURAUSKI, Kathleen; (674 pag.)WO2019/90076; (2019); 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. 951626-95-2, name is Ethyl 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 951626-95-2

To a solution of cyclopropylmethyl bromide (0.101 g, 0.75 mmol) and ethyl 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate (31.4 mg, 0.150 mmol) in acetonitrile (2 mL) was added cesium carbonate (147 mg, 0.45 mmol). The reaction mixture was heated overnight at 70 C. Upon cooling to room temperature, the insolubles were removed by filtration and the solvent evaporated to dryness to afford crude Intermediate 33.

The synthetic route of 951626-95-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Millennium Pharmaceuticals, Inc.; US2011/251184; (2011); 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 939412-86-9 as follows. Product Details of 939412-86-9

(f) (6R,8aS)-N-((3-chloropyrazin-2-yl)methyl)-3-oxooctahydroindolizine-6-carboxamide 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 CH2Cl2 (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 (11.15 g, 36.1 mmol, 91% yield) as a white solid. LC-MS: Ret. time 1.09 min; m/z 309.11 (M+H)+; 1HNMR (CDCl3, 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, 1), 4.29 (1H, dd, J=13 and 4.5 Hz), 3.42-3.47 (m, 1), 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).

According to the analysis of related databases, 939412-86-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; KIM, RONALD M.; Liu, Jian; Gao, Xiaolei; Boga, Sobhana Babu; Guiadeen, Deodialsingh; Kozlowski, Joseph A.; Yu, Wensheng; Anand, Rajan; Yu, Younong; Selyutin, Oleg B.; Gao, Ying-Duo; Wu, Hao; Liu, Shilan; Yang, Chundao; Wang, Hongjian; US2014/206681; (2014); 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. 762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. COA of Formula: C6H8ClF3N4

2,4, 5-TRIFLUOROPHENYLACETIC acid (2-1) (150 g, 0.789 MOL), Meldrum’s acid (125 g, 0.868 mol), and 4- (DIMETHYLAMINO) pyridine (DMAP) (7.7 g, 0063 mol) were charged into a 5 L three-neck flask. N, N-DIMETHYLACETAMIDE (DMAC) (525 mL) was added in one portion at room temperature to dissolve the solids. N, N-DIISOPROPYLETHYLAMINE (282 mL, 1.62 mol) was added in one portion at room temperature while maintaining the temperature below 40 C. Pivaloyl chloride (107 ML, 0.868 mol) was added dropwise over 1 to 2 h while maintaining the temperature between 0 and 5 C. The reaction mixture was aged at 5 C for 1 h. Triazole hydrochloride 1-4 (180 g, 0.789 mol) was added in one portion at 40-50 C. The reaction solution was aged at 70 C for several h. 5% Aqueous sodium hydrogencarbonate solution (625 ML) was then added dropwise at 20-45 C. The batch was seeded and aged at 20-30 C for 1-2 h. Then an additional 525 mL of 5% aqueous sodium hydrogencarbonate solution was added dropwise over 2-3 h. After aging several h at room temperature, the slurry was cooled to 0-5 C and aged 1 h before filtering the solid. The wet cake was displacement-washed with 20% aqueous DMAC (300 mL), followed by an additional two batches of 20% aqueous DMAC (400 mL), and finally water (400 mL). The cake was suction-dried at room temperature. The isolated yield of final product 2-3 was 89%.

The synthetic route of 762240-92-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK & CO., INC.; WO2005/3135; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 36070-80-1, name is 5-Chloropyrazine-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. Safety of 5-Chloropyrazine-2-carboxylic acid

Step 2: Preparation of 5-methoxypyrazine-2-carboxylic acid [0171] To a solution 5-chloropyrazine-2-carboxylic acid (7 g, 44.15mmol) in methanol (55 mL) was added concentrated sulphuric acid (0.4 mL) and heated at 65 C for 4 h. The reaction mixture was cooled to room temperature and diluted with methanol (15 mL). Then a solution of sodium methoxide in methanol (8.58 g , 158.94 mmol, 35 mL) was added and the reaction mixture was stirred at room temperature for 30 minutes. Sodium hydroxide (2.825 g , 70.643mmol) in 30 ml water was added into the reaction mixture followed by addition of 40 mL water. Then the reaction mixture was heated at 40 C for 1 h and concentrated to remove methanol. The residue was diluted with water, acidified with 38% aqueous hydrochloric acid solution (pH 2-3) and extracted ethyl acetate (600 mL x 3). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound 5-methoxypyrazine-2-carboxylic acid (6.43 g, 94% yield) as an orange solid. Calculated M+H: 155.04; Found M+H: 155.1.

The synthetic route of 5-Chloropyrazine-2-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MNEMOSYNE PHARMACEUTICALS, INC.; ANDERSON, David R.; VOLKMANN, Robert A.; MENNITI, Frank S.; WO2015/48507; (2015); A1;,
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. 19847-12-2, name is Pyrazinecarbonitrile, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: Pyrazinecarbonitrile

Pyrazine-2-carbonitrile 1g (10.5 g, 100 mmol) was dissolved in 150 mL of 1,4-dioxane under stirring, then Raney nickel (1.0 g) was added into a 250 mL autoclave. The reaction mixture was hydrogenated for 8 hours under 40 atmosphere at 60 C, filtered and concentrated under reduced pressure to obtain the title compound C-pyrazin-2-yl-methylamine 1h (10.7 g, yield 98%) as a brown oil. MS m/z (ESI): 110 [M+1]

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 19847-12-2.

Reference:
Patent; Jiangsu Hengrui Medicine Co., Ltd.; Shanghai Hengrui Pharmaceutical Co. Ltd.; EP2230241; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 33332-28-4, name is 2-Amino-6-chloropyrazine, 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. HPLC of Formula: C4H4ClN3

To a solution of 2-amino-6-chloropyrazine (6 g.) in acetonitrile (50 ml.) was added 2,2,2-trifluoroethylisothiocyanate (6 ml.) and the mixture heated under reflux on a steam bath for 6 hours. The mixture was allowed to cool, the resulting solid filtered and recrystallized from toluene to give 2-chloro-6-(3-[2,2,2-trifluoroethyl]thioureido)pyrazine.

The synthetic route of 2-Amino-6-chloropyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Imperial Chemical Industries PLC; US4447441; (1984); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 56423-63-3, 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 56423-63-3 as follows.

Under nitrogen atmosphere,4-nitrochlorobenzene (10 mg, 0.5 mmol),Potassium ethyl xanthate(80 mg, 0.5 mmol),N, N-dicarboximide (2 ml) was added to the dried reaction tube,The reaction was stirred for 2 h at 40 C in an oil bath.After the reaction system was cooled to room temperature,2-Bromopyrazine (80 mg, 0.5 mmol) was added to the reaction tube,Suspended in oil bath at 80 C for 12 h.After the reaction system was cooled,15 ml of 7K,The aqueous phase was extracted three times with 30 ml of ethyl acetate,The organic phases were combined,The solvent was evaporated under reduced pressure,Column chromatography gave a yellow solid(4-nitrophenyl)(2′ – pyrazinyl)Sulfide (lllmg, received95%).

According to the analysis of related databases, 56423-63-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Yichun University; Zhu, Qiming; Yuan, Qinghe; Chen, Ye; (9 pag.)CN105218418; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem