Category: 36070-80-1

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. category: Pyrazines

To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added 5-chloropyrazine-2-carboxylic acid (1.0 eq), DMF (0.069 eq) and toluene (5.52 vols) under a nitrogen atmosphere. The mixture was heated to 60-65 C., and thionyl chloride (1.5 eq) added drop-wise to the batch over approximately 2 hours. The thionyl chloride was washed into the flask with toluene (0.2 vols). The reaction mixture was heated at 60-65 C. for at least 4 hours, then cooled to 40-45 C. and distilled under vacuum, removing approximately 4.5 vol distillates, and distilling to a final volume of 3.2 vols. Toluene (10.6 vol) was added, and the mixture distilled under vacuum at 40-45 C., removing approximately 9.1 vol distillates, and distilling to a final volume of 4.7 vols. The mixture was then cooled to 20-25 C., and dichloromethane (10.6 vols) added. The mixture was cooled to 0-5 C. Meanwhile, to a second flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added azetidine hydrochloride (0.284 eq), dichloromethane (5.2 vols) under a nitrogen atmosphere. Triethylamine (2.57 eq) was added over at least 15 minutes maintaining the reaction temperature from 20-25 C., the triethylamine was washed into the flask with dichloromethane (0.13 vols), and the mixture cooled to -5 C. to -10 C. The acid chloride solution in the first flask was added to the second flask in portions maintaining the reaction temperature at -5 C. to -10 C. over a time period of 2-5 hours. The pH was tested and adjusted to pH>7 after the acid chloride addition. The reaction mixture was agitated for at least 30 minutes at -5 C. to -10 C. Water (10.6 vols) was added to the second flask and the temperature was allowed to increase to 20-25 C. The mixture was agitated for approximately 25 minutes and then the layers were separated. A 3.17% w/w solution (1.46 eq) of hydrochloric acid (prepared from 32% w/w hydrochloric acid and water) was added to the organic layer B keeping the batch temperature at 20-25 C. The mixture was agitated for 30 minutes at this temperature. The layers were separated, and the organic phase was treated with 26% w/w sodium chloride solution (approximately 8.9 vols) and the batch agitated at 20-25 C. for at least 15 minutes. The layers were separated and the organic layers was heated to reflux, and dichloromethane was removed by atmospheric distillation, distilling to a final volume of approximately 1-2 vols, collecting approximately 11.9 vols distillates. The resulting mixture was cooled to 20-25 C., and heptane (10.5 vols) added. The mixture was heated to reflux for 60 minutes, and then cooled to 90-100 C. The hot solution was filtered through a filter containing 10% w/w of activated charcoal into a clean dry vessel. The filter was washed with heptane (0.43 vols) and the solution cooled to 20-25 C. over at least 2 hours. The resulting crystallised slurry was filtered, and the solid washed with pentane (0.94 vols). After drying in the vacuum oven at 40 C. overnight, the desired product was obtained as a solid (corrected yield 65-78%). 1H NMR delta (400 MHz CDCl3): 2.35-2.42 (2H, m), 4.26 (2H, t), 4.67 (2H, t), 8.52 (1H, d), 9.09 (1H, d); m/z 198 (M+H)+.

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

Reference:
Patent; AstraZeneca AB; US2010/210841; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 36070-80-1, 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. 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

General procedure: The corresponding substituted salicylanilide 2 (1 mmol) and 5-chloropyrazine-2-carboxylic acid 1 (1 mmol) were dissolved in dryDMF (8 mL), the solution was cooled to 10 C and DCC (1.2 mmol)was added in three portions during 1 h. The mixture was stirred foradditional 3 h at the same temperature and then stored at 4 C for20 h. The precipitate of N,N0-dicyclohexylurea was removed byfiltration and the solvent was evaporated in vacuo till dryness. Thecrude products 3 were purified by one or repeated crystallizationfrom ethyl acetateehexane mixture. 4.1.4.1 4-Chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl 5-chloropyrazine-2-carboxylate (3a) White solid; yield: 35%; mp: 163.4-165.0 C. IR (ATR): 3372 (NH), 3081, 2934, 2857, 1751 (C=O ester), 1663, 1648, 1633, 1600, 1530, 1520, 1477, 1411, 1323, 1297, 1274, 1259, 1190, 1163, 1125, 1104, 1066, 1020, 879, 839, 826, 786, 715, 702, 668. 1H NMR (500 MHz, DMSO-d6): delta 9.40 (1H, bs, NH), 9.23 (1H, d, J = 1.4 Hz, H3″), 8.69 (1H, d, J = 1.4 Hz, H5″), 8.13 (1H, d, J = 2.6 Hz, H3), 7.78 (2H, d, J = 8.4 Hz, H3′, H5′), 7.61 (2H, d, J = 8.3 Hz, H2′, H6′), 7.57 (1H, dd, J = 2.5 Hz, J = 8.6 Hz, H5), 7.52 (1H, d, J = 8.7 Hz, H6); 13C NMR (126 MHz, CDCl3): delta 161.43, 160.35, 154.25, 146.70, 146.04, 144.31, 140.76, 139.71, 132.72, 131.40, 127.46, 126.66 (q, J = 32.8 Hz), 126.19 (q, J = 3.8 Hz), 123.93 (q, J = 272.6 Hz), 123.92, 120.45. MSmonoisotopic (calc/meas): 455.0/455.2; Anal. Calcd. for C19H10ClF3N3O3 (456.20): C, 50.02; H, 2.21; N, 9.21; Found: C, 50.34; H, 2.45; N, 9.43.

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, 5-Chloropyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Baranyai, Zsuzsa; Kratky, Martin; Vin?ova, Jarmila; Szabo, Nora; Senoner, Zsuzsanna; Horvati, Kata; Stola?ikova, Ji?ina; David, Sandor; Bosze, Szilvia; European Journal of Medicinal Chemistry; vol. 101; (2015); p. 692 – 704;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 36070-80-1, The chemical industry reduces the impact on the environment during synthesis 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, I believe this compound will play a more active role in future production and life.

To a suspension of 5-chloropyrazine-2-carboxylic acid (3.00 g, 18.92 mmol) in Dichloromethane (35 mL) and DMF (0.15 mL) at rt was added oxalyl chloride (2.411 mL, 21.76 mmol) dropwise over 10 mm. The mixture was stirred at rt for 2 h before it was concentrated under vacuum to dryness. The residue was dissolved in dichloromethan (35 mL). dimethylamine in THF (11.83 mL, 23.65 mmol) was was added at rt over 10mm, followed by the addition of triethylamine (5.80 mL, 41.6 mmol). The mixture was stirred at rt for 3 h. The mixture was diluted with ethyl acetate (50 mL) and filtered through Celite. The filtrate was concentrated under vacuum to dryness, and the residue was applied to ISCO (220 g silica gel, solid loading, 70-100% ethyl acetate) to provide the desired product, 5-chloro-N,N-dimethylpyrazine-2-carboxamide (3.18 g, 17.13 mmol,91 % yield), as a white solid.

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, 5-Chloropyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; LIU, Chunjian; LIN, James; MOSLIN, Ryan M.; WEINSTEIN, David S.; TOKARSKI, John S.; WO2015/89143; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 36070-80-1,Some common heterocyclic compound, 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, molecular formula is C5H3ClN2O2, 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.

Oxalyl chloride (1.7 mL, 19 mmol) was added to a suspension of 5-chloropyrazine-2- carboxylic acid (CAS no. 36070-80-1) (2.53 g, 16.0 mmol) in dichloromethane (25 mL) and DMF (4 drops) at RT and under argon. The mixture was allowed to stir for 1.5h, concentrated in vacuo to and the residue was re-dissolved in dichloromethane (25 mL). Dimethylamine (2M in THF, 8.77 mL, 17.6 mmol) was then added dropwise followed by triethylamine (4.9 mL, 35 mmol) and allowed to stir for a further 5.5 hours. The reaction mixture was concentrated in vacuo and the residue was re-dissolved in dichloromethane and filtered. The filtrate was chromatographed on silica, eluting with a gradient of 50- 100% ethyl acetate in isohexanes to give the desired compound (1.88 g).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Chloropyrazine-2-carboxylic acid, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2008/50117; (2008); 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. 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, A new synthetic method of this compound is introduced below., Recommanded Product: 36070-80-1

Step E: 5-Chloro-pyrazine-2-carbonyl chloride. A suspension of 5-chloro-pyrazine-2-carboxylic acid (2.49 g, 15.7 mmol) in thionyl chloride (15 mL) was heated to reflux for 1 h. The solid slowly dissolved. The bulk of the thionyl chloride was removed in vacuo, and the final traces of thionyl chloride were removed in vacuo as an azeotrope with toluene by addition of toluene and subsequent concentration repeated three times. The acid chloride was thus obtained as a reactive, yellow semi-solid. 1H NMR (400 MHz, CDCl3): delta 9.09 (d, J=1.3 Hz, 1H), 8.77 (d, J=1.3 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; Allison, Brett D.; Grice, Cheryl A.; Letavic, Michael A.; US2009/131416; (2009); 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. 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, A new synthetic method of this compound is introduced below., Safety of 5-Chloropyrazine-2-carboxylic acid

To a solution of 5-chloropyrazine-2-carboxylic acid (2 g) in dichloromethane (20 mL) were added DMF (0.05 mL) and oxalyl chloride (1.3 mL), followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure and azeotroped with toluene. To the residue was added dichloromethane (20 mL), followed by ice-cooling, and triethylamine (4 mL) and ethyl (2E)-amino(hydroxy)iminoacetate (2 g) were added thereto, followed by stirring at the same temperature for 15 minutes. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with chloroform. The solid remaining in the aqueous layer was collected by filtration and dried under reduced pressure to obtain ethyl (2E)-amino({[(5-chloropyrazin-2-yl)carbonyl]oxy}imino)acetate (1.4 g) as a colorless solid. Further, the organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain ethyl (2E)-amino({[(5-chloropyrazin-2-yl)carbonyl]oxy}imino)acetate (1.9 g) as a yellow solid.

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; Astellas Pharma Inc.; EP2511265; (2012); 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

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. 36070-80-1 name is 5-Chloropyrazine-2-carboxylic acid, 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. 36070-80-1

General procedure: The corresponding substituted salicylanilide 2 (1 mmol) and 5-chloropyrazine-2-carboxylic acid 1 (1 mmol) were dissolved in dryDMF (8 mL), the solution was cooled to 10 C and DCC (1.2 mmol)was added in three portions during 1 h. The mixture was stirred foradditional 3 h at the same temperature and then stored at 4 C for20 h. The precipitate of N,N0-dicyclohexylurea was removed byfiltration and the solvent was evaporated in vacuo till dryness. Thecrude products 3 were purified by one or repeated crystallizationfrom ethyl acetateehexane mixture.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Chloropyrazine-2-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Article; Baranyai, Zsuzsa; Kratky, Martin; Vin?ova, Jarmila; Szabo, Nora; Senoner, Zsuzsanna; Horvati, Kata; Stola?ikova, Ji?ina; David, Sandor; Bosze, Szilvia; European Journal of Medicinal Chemistry; vol. 101; (2015); p. 692 – 704;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

36070-80-1, 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 36070-80-1 as follows.

In a sealed tube, Intermediate 30 (0.58 g, 1.079 mmol) was dissolved in DMF (5.39 mL). To the resulting solution was added 5-chloropyrazine-2-carboxylic acid (0.188 g, 1.187 mmol), HATU (0.615 g, 1.618 mmol), and pyridine (0.262 mL, 3.24 mmol). The reaction was stirred at 20 C. for 2 hours. The reaction was extracted into ethyl acetate, washed once with water, once with brine, dried with sodium sulfate, filtered through a fritted funnel, and concentrated. The crude material was eluted through a silica gel column using 0-50% EtOAc/Heptane. The desired fractions were combined and concentrated to yield tert-butyl N-[(4aR,6S,11bR)-10-[(5-chloropyrazine-2-carbonyl)amino]-3,3,6,11b-tetramethyl-4,4-dioxo-5,6-dihydro-4-aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (0.640 g, 0.944 mmol, 87% yield) as an off-white solid.

According to the analysis of related databases, 5-Chloropyrazine-2-carboxylic acid, the application of this compound in the production field has become more and more popular.

Reference:
Patent; WHITE, Ryan; ALLEN, Jennifer R.; EPSTEIN, Oleg; HONG, Fang-Tsao; HUA, Zihao; HUMAN, Jason Brooks; LOPEZ, Patricia; OLIVIERI, Philip R.; ROMERO, Karina; SCHENKEL, Laurie; STELLWAGEN, John; TAMAYO, Nuria A.; ZHENG, Xiao Mei; US2014/213581; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

36070-80-1,Some common heterocyclic compound, 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, molecular formula is C5H3ClN2O2, 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.

5-(Cyclopropylmethoxy)pyrazine-2-carboxylic acid A solution of 5-chloropyrazine-2-carboxylic acid (1.00 g, 6.31 mmol), cyclopropyl carbinol (1.00 mL, 12.4 mmol) and potassium tert-butoxide (2.00 g, 17.8 mmol) in dimethylformamide (20.0 mL) is heated at 100 C. for 3 hours. The reaction is cooled to room temperature, quenched with 1M hydrochloric acid. The mixture is extracted with ethyl acetate and isopropyl alcohol/chloroform (1/10), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give the title compound (1.10 g, 90%) as a grayish solid. This acid is used directly without further purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Chloropyrazine-2-carboxylic acid, its application will become more common.

Reference:
Patent; GREEN, Steven James; HEMBRE, Erik James; MERGOTT, Dustin James; SHI, Yuan; WATSON, Brian Morgan; WINNEROSKI, JR., Leonard Larry; US2014/371212; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem