Month: July 2021

Reference of 33332-25-1, 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. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

(5-chloropyrazin-2-yl)methyl methanesulfonate; [00369] To a solution of 5-chloropyrazine-2-carboxylic acid (3.21 g, 20.3 mmol) in diethyl ether (20 mL) and methanol (20.0 mL) was added a 2M solution in diethyl ether of trimethylsilyldiazomethane (20.3 mL, 40.5 mmol). A vigorous bubbling was observed initially, and LCMS after 30 minutes indicated that the reaction was complete.Concentration of the reaction mixture afforded methyl 5-chloropyrazine-2-carboxylate (3.53 g, 20.5 mmol, 101% yield) as a tan solid. This material was shown to be >95% pure by NMR analysis and was used in the subsequent step without any purification. lH NMR (400 MHz, CDC13) delta (ppm): 9.09 (s, 1H), 8.70 (s, 1H), 4.04 (s, 3H).[00370] To a 0 C solution of methyl 5-chloropyrazine-2-carboxylate (3.50 g, 20.3 mmol) in tetrahydrofuran (101 mL) was added a 1M solution in tetrahydrofuran of diisobutylaluminum hydride (42.6 mL, 42.6 mmol). The reaction was stirred at 0 C for 2 hours, after which it was quenched by the addition of methanol (2 mL). To this mixture was added saturated sodium-potassium tartrate solution, and the resulting reaction mixture was extracted with ethyl acetate (3 x 100 mL), dried (sodium sulfate), filtered and concentrated to brown residue. Purification was achieved by column chromatography on silica gel (Luknova 120 g, 20 mL/min) using 30 to 100% ethyl acetate in hexanes over 60 minutes to afford (5- chloropyrazin-2-yl)methanol (1.45 g, 10.0 mmol, 50 % yield) as a tan solid. NMR (400 MHz, CDC13) a (ppm): 8.56 (s, 1H), 8.45 (s, 1H), 4.84 (s, 3H), 2.79 (br. s, 1H).[00371] To a 0 C solution of (5-chloropyrazin-2-yl)methanol (648 mg, 4.48 mmol) in dichloromethane (12 mL) was added triethylamine (1.87 mL, 13.5 mmol) followed by dropwise addition of methanesulfonyl chloride (0.699 mL, 8.97 mmol). After 20 minutes, analysis by LCMS indicated the complete conversion to the mesylate product. The reaction mixture was concentrated to afford (5-chloropyrazin-2-yl)methyl methanesulfonate (787 mg, 3.53 mmol, 79% yield) as an oil. The material was used crude in the next step without further purification.

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, Methyl 5-chloropyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; IRONWOOD PHARMACEUTICALS, INC.; HUDSON, Colleen; BARDEN, Timothy, C.; JIA, James; MERMERIAN, Ara; PENG, Bo; YANG, Jane; YU, Xiang, Y.; SPROTT, Kevin; WO2012/88469; (2012); 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. 5521-58-4, name is 5-Methylpyrazin-2-amine, A new synthetic method of this compound is introduced below., category: Pyrazines

2-Amino-5-methyl-pyrazine (2.00 g, 21.25 mmol; CASNo. 5521-58-4) was dissolved in THF (80 mL), cooled to 0 0C, and treated with pyridine (1.77 g, 22.3 mmol) followed by the dropwise addition of phenylchloroformate (3.49 g, 22.3 mmol) in THF (30 mL). After stirring for 3 h, 100 mL of MeCN was added and the reaction mixture was reduced to a volume of 100 ml. in vacuo. The title compound as white crystals was collected by filtration (2.5 g, 55%) and was used without further purification.

The synthetic route of 5521-58-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; WO2009/127948; (2009); 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. 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., category: Pyrazines

A solution of the compound 5a (2.20g, 8.00mmol), 3-bromo-5-chloropyrazin-2-amine (1.54g, 7.27mmol), potassium acetate (2.00g, 14.54mmol), Pd (dppf) Cl2 (0.15g, 0.20mmol), H2O (2mL) in dioxane (40mL) was heated to 75 C under N2 for 4 hours. Hexane (50mL) was added, the precipitate was filtered to afford the compound 5b as a brown solid (0.79g, 36%). MS: 277 (M+H) +.

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 76537-18-3.

Reference:
Patent; JACOBIO PHARMACEUTICALS CO., LTD.; MA, Cunbo; GAO, Panliang; CHU, Jie; WU, Xinping; WEN, Chunwei; KANG, Di; BAI, Jinlong; PEI, Xiaoyan; (82 pag.)WO2017/211303; (2017); 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. 23688-89-3, name is 6-Chloropyrazine-2-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C5H3ClN2O2

6-Ch[oropyrazine-2-carboxy[ic acid [CAS RN: 23688-89-3] (700 mg, 4.42 mmo[, 1 .0 eq) in 30 mL ethyl. acetate was treated with T3P solution [50 % in ethyl acetate] (6.57 mL, 11.0 mmol, 2.5 eq) and with N-hydroxyethanimidamide [CAS10 RN: 22059-22-9] (327 mg, 4.42 mmol, 1.0 eq). The resulting solution was stirredat 65 C overnight. The reaction mixture was hydrolysed and extracted with ethyl acetate (3x). The combined organic phases were washed with a saturated sodium bicarbonate solution and with brine. The phases were separated by the use of a Whatman filter. The volatile components of the resulting organic phasewere removed in vacuo and the crude material was purified via preparative HPLC under basic conditions (column: Chromatorex C18, eluent: acetonitrile / 0.2% aqueous ammonia 15:85 -> 55:45) to give 55 mg (6% yield of theory) of the title compound.UPLC-MS (Method 2): R = 0.88 mm; MS (EI0): m/z = 197 [M+H].1H-NMR (400 MHz, DMSO-d6): oe [ppm] = 9.10 (5, 1H), 9.36 (5, 1H), 1xCH3 obscured by solvent signal.

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 23688-89-3.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BAeRFACKER, Lars; SIEMEISTER, Gerhard; HEINRICH, Tobias; PRECHTL, Stefan; STOeCKIGT, Detlef; ROTTMANN, Antje; WO2015/113927; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 4949-13-7, 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.

[0220] To a mixture of (4-bromophenyl)methanamine hydrochloride (2.2 g, 9.9 mmol, (0654) 1.0 equiv) and IPA (15 mL) in a microwave vial (20 mL) were added 2-fluoropyrazine (1.1 g, 10.9 mmol, 1.1 equiv) and DIPEA (3.1 g, 23.7 mmol, 2.4 equiv). ). The vial was sealed and heated at 170 C in a microwave reactor for 4 h. The mixture was concentrated onto 10 g of Si02 and purified by silica gel chromatography (80 g column, 0-10% MeOH in DCM) to provide 1.65 g (63%) of A-(4-bromobenzyl)pyrazin-2-amine as an off-white solid. LRMS (ES) m/z 264.0 (M+H).

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

Reference:
Patent; CYTOKINETICS, INC.; MORGAN, Bradley P.; VANDERWAL, Mark; CHUANG, Chihyuan; (0 pag.)WO2020/5888; (2020); 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 33332-25-1 as follows. Recommanded Product: Methyl 5-chloropyrazine-2-carboxylate

Synthesis of 5′-(3-{1-[4-(2-amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic Acid tert-butyl Ester A 250 ml RB flask is charged with R-7 (5.4 g, 28.99 mmol) in 100 mL of NMP. R-8 (5.00 g, 28.99 mmol) is added followed by triethylamine (4.85 ml, 34.79 mmol). The reaction is heated to 60 C. under nitrogen overnight. The reaction is cooled to room temperature, poured into ice water and the precipitated I-76 (8.60 g) is isolated by filtration; m/z 323.4 [M+H]

According to the analysis of related databases, 33332-25-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Boehringer Ingelheim International GmbH; BYLOCK, Lars Anders; US2013/195879; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 41110-29-6, 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 41110-29-6 as follows.

A solution of methyl 3-methylpyrazine-2- carboxylate (265A, 9.1 g, 59.8 mmol) in DCM (100 mL) was cooled to 0 C was added urea hydrogen peroxide adduct (7.8 g, 83.0 mmol), followed by dropwise addition of trifluoroacetic acid anhydride (10.8 mL, 78.0 mmol). The resulting mixture was stirred at 0 C for 1 h, and at RT for 18 h, during which LCMS indicated a mixture of two peaks corresponding to MS m/z = 169.0 [M+H]+. The reaction was diluted with DCM and quenched with saturated Na2SO3 solution; the aqueous layer was back-extracted with DCM (2 x). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. ISCO purification (20-80% EtOAc/hexanes) afforded a mixture of two regioisomers, containing 3-(methoxycarbonyl)-2-methylpyrazine 1 -oxide and 2- (methoxycarbonyl)-3-methylpyrazine 1 -oxide (5.2 g, 30.9 mmol, 51.7% yield). The mixture of regioisomers was taken to next step without further purification. MS m/z = 169.0 [M+H]+. A solution of the mixture of 3-(methoxycarbonyl)-2-methylpyrazine 1 – oxide and 2-(methoxycarbonyl)-3-methylpyrazine 1 -oxide (5.1 g, 15.2 mmol) in toluene (50 mL) was cooled to 0 C and phosphorus oxychloride (2.8 mL, 30.3 mmol) was added under nitrogen followed by DMF (0.12 mL, 1.52 mmol). The reaction mixture was stirred at RT for 4 h, and heated to 65 C for 18 h, cooled to RT, diluted with EtOAc and washed with saturated NaHCO3 solution. The aqueous layer was back-extracted with EtOAc (2 x). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. ISCO purification (0-50% EtOAc/hexanes) with care afforded both isomers: methyl 5-chloro-3-methylpyrazine-2-carboxylate (265B, 0.68 g) (minor product) denoted by peak 1 and methyl 6-chloro-3-methylpyrazine-2-carboxylate (265B1, 1.50 g) (major product) denoted by peak 2. MS m/z = 187.0 [M+H]+. Peak 1 : 1H NMR (300 MHz, DMSO-d6) delta 8.73 (s, 1 H), 3.91 (s, 3H), 2.71 (s, 3H). Peak 2: 1H NMR (300 MHz, DMSO-d6) delta 8.89 (s, 1 H), 3.91 (s, 3H), 2.71 (s, 3H).

According to the analysis of related databases, 41110-29-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AMGEN INC.; ALLEN, Jennifer R.; AMEGADZIE, Albert; BOURBEAU, Matthew P.; BROWN, James A.; CHEN, Jian J.; CHENG, Yuan; FROHN, Michael J.; GUZMAN-PEREZ, Angel; HARRINGTON, Paul E.; LIU, Longbin; LIU, Qingyian; LOW, Jonathan D.; MA, Vu Van; MANNING, James; MINATTI, Ana Elena; NGUYEN, Thomas T.; NISHMURA, Nobuko; NORMAN, Mark H.; PETTUS, Liping H.; PICKRELL, Alexander J.; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert M.; SIEGMUND, Aaron C.; STEC, Markian M.; WHITE, Ryan; XUE, Qiufen; (759 pag.)WO2016/22724; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 6705-33-5, 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. 6705-33-5 name is Pyrazin-2-ylmethanol, 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.

Synthesis of 2-(chloromethyl)pyrazine [0540] To a stirred solution of pyrazin-2-ylmethanol (0.3 g 2.72 mmol) in DCM (10 mL) was added SOCl2 (1 mL) at 0 C under inert atmosphere. The reaction mixture was heated up to 50 C and stirred for 2 h. After completion of starting material (by TLC), the volatiles were evaporated under reduced pressure. The residue was quenched with ice cold water followed by saturated NaHC03 and extracted with EtOAc. Combined organic layer was dried over sodium sulphate, filtered and concentrated in vacuo to obtain the crude product. The crude material was purified by silica gel column chromatography to afford 2-(chloromethyl)pyrazine (110 mg, 20.4%) as liquid. 1H-NMR (CDC13, 400 MHz): delta 8.74 (s, 1H), 8.58-8.56 (m, 2H), 4.71 (s, 2H); LC-MS: 98.86%; 129 (M++l) (column; Eclipse XDB C-18, (150×4.6 mm, 5.0mu); RT 4.83 min. 5mM NH4OAc: ACN; 1.0 ml/min); TLC: 70% EtOAc/Hexane (Rf: 0.6).

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

Reference:
Patent; ENVIVO PHARMACEUTICALS, INC.; RIPKA, Amy; SHAPIRO, Gideon; MCRINER, Andrew, J.; BURSAVICH, Matthew, Gregory; WO2013/142269; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 1458-01-1, 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. 1458-01-1, name is Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

General procedure: Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate 2 (1 eq.) was combined with K2CO3 (10 eq.), the appropriate (het)aryl boronic acid (1.5 eq.) and Pd(PPh3)4 (5 mol%) in a two-neck round bottom flask. The flask was connected to a condenser and purged with nitrogen. A 4:1 mixture of anhydrous toluene: MeOH (60 mL) was added via syringe and the reaction mixture was heated at reflux for 0.5-18 h. The mixture was allowed to cool to room temperature and filtered through Celite (10 x 3 cm, eluting with 3 x 20 mL EtOAc). The filtrate was evaporated to dryness and the residue purified by silica gel flash column chromatography using EtOAc/pet spirit.

The synthetic route of Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Article; Buckley, Benjamin J.; Majed, Hiwa; Aboelela, Ashraf; Minaei, Elahe; Jiang, Longguang; Fildes, Karen; Cheung, Chen-Yi; Johnson, Darren; Bachovchin, Daniel; Cook, Gregory M.; Huang, Mingdong; Ranson, Marie; Kelso, Michael J.; Bioorganic and Medicinal Chemistry Letters; vol. 29; 24; (2019);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, molecular formula is C6H8ClF3N4, 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 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride

The title compound was prepared using the method described in WO 2008/040974.A mixture of 3-nitropropionic acid (20.0 g, 0.168 mol), 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1 ,2,4]triazolo[4,3- a]pyrazine hydrochloride (48.0 g, 0.21 mol) in acetonitrile (400 mL) is cooled to 0 C and 4-methylmorpholine (16.9 g, 0.168 mol) is added, followed by N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC) (48.4 g, 0.25 mol) after 5 min. The resulting mixture is stirred at room temperature for 20 hours. The resulting mixture is concentrated to about 2/3 of its volume and ethyl acetate is added (750 mL). The resulting mixture is washed twice with water (200 + 100 mL), sat. aq. sodium hydrogencarbonate (200 mL), brine (200 mL) and dried with sodium sulfate. The resulting clear solution is concentrated under reduced volume and MTBE is added (100 mL). The precipitated white solid is filtered off, washed with MTBE (200 mL) and dried under reduced pressure to yield 38.8 g (79 % yield) of NTPT as white powder.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 762240-92-6, its application will become more common.

Reference:
Patent; LEK PHARMACEUTICALS D.D.; STERK, Damjan; USTAR, Matjaz; ZLICAR, Marko; WO2011/151443; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem