Month: June 2021

Synthetic Route of 63744-22-9, 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. 63744-22-9 name is 6,8-Dibromoimidazo[1,2-a]pyrazine, 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.

EXAMPLE 1Part A: The title compound was prepared according to US20060106023 (A1 ).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6,8-Dibromoimidazo[1,2-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; SCHERING CORPORATION; ALBANY MOLECULAR RESEARCH, INC.; WO2009/97233; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 21279-62-9,Some common heterocyclic compound, 21279-62-9, name is 3-Chloropyrazine-2-carboxamide, molecular formula is C5H4ClN3O, 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.

General procedure: The starting compound (1.27 mmol) was treated with 18 aliphatic amines, alicyclic amines or saturated heterocycles containing at least one nitrogen atom (2.54 mmol). Four reactions were completed by conventional heating methods. The conditions were 110 C, toluene as a solvent and pyridine (1.27 mmol) as a base. The reaction time was set to one hour. Then the reactions were completed using the microwave reactor with focused field and conditions used for syntheses were 140 C, 30 min,120 W, methanol used as a solvent and pyridine (1.27 mmol) as a base. They were set experimentally with respect to prior experience. The progress of reaction was monitored with TLC in system hexane/ethyl acetate (1:1). Then the mixture was separated by flash column chromatograph using gradient elution. Mobile phases were hexane and ethyl acetate again.

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

Reference:
Article; Jandourek, Ondrej; Dolezal, Martin; Kunes, Jiri; Kubicek, Vladimir; Paterova, Pavla; Pesko, Matus; Buchta, Vladimir; Kralova, Katarina; Zitko, Jan; Molecules; vol. 19; 7; (2014); p. 9318 – 9338;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

98-97-5, name is Pyrazine-2-carboxylic acid, 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: C5H4N2O2

General procedure: The N-hydroxysuccinimide esters of pyrazinecarboxylic acidand (S)-(+)-ibuprofen were prepared by dissolving the starting acid(0.200 g, 1.0 equiv) in dry tetrahydrofuran and setting to stir at 0C. N-Hydroxysuccinimide (1.0 equiv) was added followed by N,N0-dicyclohexylcarbodiimide (1.0 equiv). The mixture was warmedto room temperature and stirred for 24 h. The N,N?-dicyclohexylureawas removed by filtration and the filtrate was concentratedto afford a solid that was purified by column chromatography..

The synthetic route of 98-97-5 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Bakas, Nicole A.; Schultz, Chad R.; Yco, Lisette P.; Roberts, Christopher C.; Chang, Chia-en A.; Bachmann, Andre S.; Pirrung, Michael C.; Bioorganic and Medicinal Chemistry; vol. 26; 2; (2018); p. 401 – 412;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 77112-52-8, name is Ethyl imidazo[1,2-a]pyrazine-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. name: Ethyl imidazo[1,2-a]pyrazine-2-carboxylate

To a well stirred suspension of the ester obtained from step-1 (10 g, 52.3 mmol) in dioxane (400 ml) was added lithium borohydride (2 eqv) at 25 C. and the resulting reaction mixture was allowed to stir at the same temperature for 10 minutes. It was then warmed to 60 C. and kept at this temperature for 20 minutes (. Higher temperature and more reaction time reduce the yield and quality of reaction). Reaction mixture was then cooled to 0 C., acidified with 1N HCl and dioxane was completely evaporated under reduced pressure. Residue was taken in dichloromethane (200 ml), TEA (4eqv) and Boc-anhydride (1.2 eqv) was added to it and the resulting reaction mixture was allowed to stir at 25 C. for 16 hrs. Organic layer was washed with water and brine and finally dried over sodium sulfate. Evaporation of organic layer gave the crude product which was purified by column chromatography (70% ethyl acetate in hexane). Yield: 27%

The synthetic route of Ethyl imidazo[1,2-a]pyrazine-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GRUENENTHAL GmbH; US2009/186899; (2009); 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. 4949-13-7, name is 2-Fluoropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. SDS of cas: 4949-13-7

Butyl lithium solution (2.5 M in hexane, 881 mL, 2.01 mol) and 1.5 L of dry THF were charged into a flame-dried 5.0 L round bottomed flask. The flask was cooled to -50 0C and 2,2,6,6-tetramethylpiperidine (312.0 mL, 2.20 mol) was added dropwise . The reaction mixture was warmed to 0 0C without taking the cold bath away and kept at that temperature for 20 min. The reaction was then cooled to -78 0C, and 2-fluoropyrazine (180 g, 1.84 mol) in 150 mL of THF was added dropwise. The mixture was kept at -78 0C for 5 min. Iodine (464 g, 1.84 mol) in 500 mL of THF was added dropwise and the reaction mixture was kept at -78 0C for 1 h. The reaction was quenched with the addition of 250 mL of concentrated HCl, 250 mL MeOH and 250 mL THF at -78 0C. The cold bath was then removed, and aqueous sodium bisulfite was added to get rid of traces of unreacted iodine. The solvent was evaporated and the residue was diluted with water and adjusted to pH 8. The mixture was extracted with ethyl acetate (3 x 1.5 L). Combined ethyl acetate layer was dried over sodium sulfate and concentrated. The crude product was purified by column chromatography (Silica: 100-200 mess, solvent: 10% EtOAc/hexanes) to give the title compound as a white solid.

The synthetic route of 4949-13-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMGEN INC.; ALLEN, Jennifer R.; BOURBEAU, Matthew P.; CHEN, Ning; HU, Essa; KUNZ, Roxanne; RUMFELT, Shannon; WO2010/57121; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 36070-75-4,Some common heterocyclic compound, 36070-75-4, name is 5-Chloropyrazine-2-carbonitrile, molecular formula is C5H2ClN3, 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 mixture of 3-hydroxy-5-isopropoxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (492 mg), potassium carbonate (445 mg), and N-methylpyrrolidone (NMP) (4 mL) was added a solution of 5-chloropyrazine-2-carbonitrile in NMP (3 mL) under ice-cooling, followed by stirring at room temperature for 4 hours and at 50C for 20 minutes. Diethyl ether (20 mL) and water (20 mL) were added thereto to carry out liquid separation, the organic layer was washed with water (20 mL) and saturated brine (20 mL) in this order, and the aqueous layer was extracted again with diethyl ether (20 mL). The combined organic layer was dried over anhydrous magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane-ethyl acetate=1:1 to 1:2) to obtain 3-[(5-cyanopyrazin-2-yl)oxy]-5-isopropoxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (632 mg) as a light yellow oil.

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-carbonitrile, its application will become more common.

Reference:
Patent; Astellas Pharma Inc.; EP2511265; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 76537-18-3, These common heterocyclic compound, 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, 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.

Intermediate C65-Chloro-3-(2-methylthiazol-5-yI)pyrazi n-2-am i ne A mixture of 2-methyl-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)thiazole (1 g, 4.44 mmol), 3-bromo-5-chloropyrazin-2-amine (0.926 g, 4.44 mmol), PdCI2(dppf).CH2CI2 adduct (0.181 g, 0.222 mmol) and 2 M Na2CO3 (6.66 ml) in DME (22.21 ml) under N2 was heatedusing microwave radiation at 120C for 45 mins. The mixture was added to water (100 ml) and extracted with EtOAc (2 x 90 ml). The organic extracts were washed with brine, dried over Mg504 and concentrated under reduced pressure. Purification by chromatography on silica eluting with 0-10% [2.OM NH3 in MeOH] in TBME afforded the title compound as a brown solid;LCMS: Rt 0.87 mins; MS mlz 227.1 [M+H]+; Method 2minLC_v003.

The synthetic route of 76537-18-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; BELLENIE, Benjamin Richard; BLOOMFIELD, Graham Charles; BRUCE, Ian; CULSHAW, Andrew James; HALL, Edward Charles; HOLLINGWORTH, Gregory; NEEF, James; SPENDIFF, Matthew; WATSON, Simon James; (395 pag.)WO2015/162459; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 24241-18-7, These common heterocyclic compound, 24241-18-7, name is 2-Amino-3,5-dibromopyrazine, 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.

Zn dust (2 g, 30.6 mmol, 3.8 eq. ) and I2 (200 mg, 10percent of Zn) were added to a dry 100 mL two-necked round bottom flask under argon atmosphere. 12 mL of anhydrous THF and 8 mL of dry DMF were successively added using a syringe. The mixture was stirred at RT until the brown color of I2 disappeared. Then benzylbromide(1.5 mL, 12 mmol, 1.5 eq.) was added using a syringe and the reaction mixture was stirred at 85 °C for 3 h. After insertion of Zn, the reaction mixture was cooled to RT and 2-amino-3,5-dibromopyrazine (2g, 8 mmol, 1.0 eq.) and bis(triphenylphosphine)palladium(II) chloride (220 mg, 0.31 mmol , 11 percent of pyrazine) in 18 mL of anhydrous THF and 12 mL of dry DMF were added. The reaction mixture was continuously stirred at RT for 12 h.Then the mixture was filtered by diatomite. The filtrate was poured in 50 mL of water and extracted with ethyl acetate (3*30 mL). The organic fractions were combined and dried over anhydrous sodium sulfate and then concentrated on a rotary evaporator. The resulting residue was purified by silica gel column chromatography using petroleum ether/ethyl acetate (3/1,v/v ), affording 3-benzyl-5-bromopyrazine-2-amine (5) as a yellow viscous oil (1.8 g, 84.9percent). 1H NMR (CDCl3, 300 MHz): delta 4.10 (s, 2H,CH2), 4.60 (br s, 2H, NH2),7.10-7.41 (m, 5H, Ar-H), 8.15 (s, 1H, Ar-H); ESI-MS calcd. for C11H10BrN3: 263.0, found: 264.3 (M+H+).

The synthetic route of 24241-18-7 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Yuan, Ming-Liang; Jiang, Tian-Yu; Du, Lu-Pei; Li, Min-Yong; Chinese Chemical Letters; vol. 27; 4; (2016); p. 550 – 554;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 939412-86-9, A common heterocyclic compound, 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, molecular formula is C5H7Cl2N3, 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.

A mixture of trans-4-oxooctahydropyrido[2,l-c][l,4]oxazine-7-carboxylic acid (2.2 g, 11.0 mmol), (3-chloropyrazin-2-yl)methanamine hydrochloride (2.2 g, 3.70 mmol), HATU (6.3 g, 16.6 mmol ) and triethylamine (4.7mL, 33.1 mmol ) in dichloromethane (100 mL) was stirred at room temperature for 4 hours. The reaction mixture was washed with water (150 mL) and extracted with dichloromethane (50 mLx 3) and the combined organic layers were concentrated in vacuo to afford the crude product, which was purified by silica gel column chromatography (THF: PE = 10%~100%) to give trans-N-((3-chloropyrazin-2-yl)methyl)-4-oxooctahydropyrido[2,l- c][l,4]oxazine-7-carboxamide (2.1 g, 58.3% yield).1HNMR (400 MHz, CD3OD): delta =8.54 (d, J=2.4 Hz, 1H), 8.34 (d, J=2.3 Hz, 1H), 4.74 (dt, J=12.9, 1.9 Hz, 1H), 4.60-4.67 (m, 2H), 4.11 (s, 2H), 4.02 (dd, J=11.9, 4.3 Hz, 1H), 3.56-3.65 (m, 2H), 3.43-3.53 (m, 1H), 2.67-2.76 (m, 1H), 2.49 (tt, J=11.8, 3.7 Hz, 1H), 2.05-2.15 (m, 1H), 1.77-1.88 (m, 2H), 1.50 ppm (dd, J=l 1.8, 3.9 Hz, 1H). MS (ESI): M/Z (M+l): 325.1.

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; MERCK SHARP & DOHME CORP.; WU, Hao; KIM, Ronald M.; LIU, Jian; GAO, Xiaolei; BOGA, Sobhana Babu; GUIADEEN, Deodialsingh; LIU, Shilan; YANG, Chundao; WANG, Hongjian; WO2014/113932; (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. 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

To a suspension of 5-chloropyrazine-2-carboxylic acid (1.00 g, 631 mmol) in dichloromethane (12 mL) and DMF (0.015 mL) at rt was added oxalyl chloride (0.804 mL, 7.25 mmol) drop wise over 10 min. The mixture was stirred at rt for 2 h before it was concentrated under vacuum to dryness. Tire residue was dissolved in dichloromethan (15 mL). Dimethylamine in THF (3.94 mL, 7.88 mmol) was added at rt over 10 min, followed by triethylamine (1.934 mL, 13.88 mmol). The mixture was stirred at rt for 2 h. The mixture was diluted with ethyl acetate (50 mL) and filtered through Cehte. The filtrate was concentrated under vacuum to dryness, and the residue was applied to flash chromatograph (80 g silica gel, solid loading, 65-100% ethyl acetate) to provide the desired product, 5-chloro-N,N-dimethylpyrazine-2-carboxamide (1.07 g, 5.76 mmol, 91 % yield), as a white solid. LCMS m z 186.1 (M+H)+.

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; BRISTOL-MYERS SQUIBB COMPANY; XIAO, Zili; YANG, Michael G.; LIU, Chunjian C.; SHERWOOD, Trevor C.; GILMORE, John L.; WEINSTEIN, David S.; (152 pag.)WO2019/183186; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem