Month: May 2021

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. 767340-03-4, name is (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine, A new synthetic method of this compound is introduced below., SDS of cas: 767340-03-4

Step C: Preparation of (2R)-4-OXO-4-F3- (TRIFLUOROMETHYL)-5, 6- DIHYDROF L, 2. 41TRIAZOLOR4, 3-ALPVRAZIN-7 (8H)-YLL-1-(24*5- TRIFLUOROPHENYL) butan-2-amine (2-5) Into a 500 ml flask were charged chloro (1, 5-cyclooctadiene) rhodium (I) dimer {[Rh (cod) CI] 2} (292 mg, 0.59 mmol) and (R, S) t-butyl Josiphos (708 mg, 1.31 mmol) under a nitrogen atmosphere. Degassed MEOH was then added (200 ML) and the mixture was stirred at room temperature for 1 h. Into a 4 L HYDROGENATOR was charged the enamine amide 2-4 (118 g, 0.29 mol) along with MEOH (1 L). The slurry was degassed. The catalyst solution was then transferred to the hydrogenator under nitrogen. After degassing three times, the enamine amide was hydrogenated under 200 psi hydrogen gas at 50 C for 13 h. Assay yield was determined by HPLC to be 93% and optical purity to be 94% ee. The optical purity was further enhanced in the following manner. The methanol solution from the hydrogenation reaction (18 g in 180 mL MEOH) was concentrated and switched to methyl t-butyl ether (MTBE) (45 mL). Into this solution was added aqueous H3PO4 solution (0.5 M, 95 mL). After separation of the layers, 3N NAOH (35 ML) was added to the water layer, which was then extracted with MTBE (180 mL + 100 mL). The MTBE solution was concentrated and solvent switched to hot toluene (180 mL, about 75 C). The hot toluene solution was then allowed to cool to 0 C slowly (5-10 h). The crystals were isolated by filtration (13 g, yield 72%, 98-99% ee); m. p. 114.1-115. 7 C. 1H NMR (300 MHZ, CD3CN) : 5 7.26 (m), 7.08 (m), 4.90 (s), 4.89 (s), 4.14 (m), 3.95 (m), 3.40 (m), 2. 68 (m), 2.49 (m), 1.40 (bs). Compound 2-5 exists as amide bond rotamers. Unless indicated, the major and minor rotamers are grouped together since the carbon-13 signals are not well resolved: 13C NMR (CD3CN) : 8 171.8, 157.4 (ddd, JCF = 242.4, 9.2, 2.5 HZ), 152.2 (major), 151.8 (minor), 149.3 (DDD ; JCF = 246.7, 14.2, 12.9 Hz), 147.4 (ddd, JCF = 241.2, 12.3, 3.7 Hz), 144.2 (q, JcF = 38. 8 Hz), 124.6 (ddd, JCF = 18. 5,5. 9,4. 0 Hz), 120.4 (dd, JCF = 19.1, 6.2 Hz), 119.8 (q, JCF = 268. 9 Hz), 106.2 (dd, JCF = 29.5, 20.9 Hz), 50.1, 44.8, 44.3 (minor), 43.2 (minor), 42.4, 41.6 (minor), 41.4, 39.6, 38. 5 (minor), 36.9. The following high-performance liquid chromatographic (HPLC) conditions were used to determine percent conversion to product: Column: Waters Symmetry C18, 250 mm x 4.6 mm Eluent: Solvent A: 0.1 vol% HC104/H20 Solvent B : acetonitrile Gradient: 0 min 75% A: 25% B 10 min 25% A: 75% B 12. 5 MIN 25% A: 75% B 15 MIN 75% A: 25% B Flow rate: 1 ML/MIN Injection Vol.: 10 uL UV detection: 210 nm Column temp.: 40 C Retention times: compound 2-4: 9.1 min compound 2-5 : 5.4 min tBu Josiphos: 8.7 min The following high-performance liquid chromatographic (HPLC) conditions were used to determine optical purity: Column: Chirapak, AD-H, 250 mm x 4.6 mm Eluent: Solvent A: 0.2 vol. % diethylamine in heptane Solvent B: 0.1 vol% diethylamine in ethanol Isochratic Run Time: 18 min Flow RATE : 0. 7 mL/min Injection Vol.: 7 uL W detection: 268 nm Column temp.: 35 C Retention times: (-amine 2-5: 13.8 min (-amine : 11.2 min EXAMPLE 2 Methyl (3S)-3-AMINO-3-(6-METHOXYPERIDIN-3-YL) PROPANOATE (3-2) Into a 7 mL vial were charged chloro (1, 5-CYCLOOCTADIENE) rhodium (I) dimer { [Rh (cod) CI] 2} (14.2 mg, 0.029 mmol) and (R, S)-t-Bu Josiphos (31.3 mg, 0.058 mmol) under a nitrogen atmosphere. Degassed methanol (1 mL) was then added and the catalytic complex was stirred for 45 min at room temperature. In a separate 2-mL vial, the enamine ester 3-1 (0.1 g, 0.5 mmol) was dissolved in 0.9 mL distilled 2,2, 2-trifluoroethanol. To the same vial 0.1 RNL of the prepared catalyst solution was added resulting in 1 mol% catalyst loading and a 2,2, 2- trifluoroethanol/methanol mixture of 90/10. The hydrogenation vial was then sealed and transferred into the hydrogenation bomb under nitrogen. After degassing three times with hydrogen, the enamine ester was hydrogenated under 90-psig-hydrogen gas at 50 C for 13.5 h. Assay yield was determined by HPLC to be 88% and optical purity to be 89% ee. 1H-NMR (400 MHz, CDCl3) : 8 1.81 (bs, 2H), 2.64 (m, 2H), 3.68 (s, 3H), 3.91 (s, 3H), 4.4 (dd, 1H), 6.72 (d, 1H), 7.62 (dd, 1H), and 8. 11 (s, 1H) ppm.

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 & CO. INC.; WO2004/85378; (2004); 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. 33332-28-4, name is 2-Amino-6-chloropyrazine, This compound has unique chemical properties. The synthetic route is as follows., Safety of 2-Amino-6-chloropyrazine

To a mixture of compound 9 (312.0 g, 2A mol) and K2C03 (664.0 g, 4.8 mol) in MeCH(1.0 L) was dropwise added lCl (704.0 g, 4.3 mol in 1.0 L of DCM) over 2 hours0C. Then the reaction mixture was stirred at room temperature overnight. Thereaction was quenched with Na2SO3 aqueous solution (2M, 1 .5 L). The mixture was extracted with DCM (1.0 L x 3). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purifiedcolumn chromatography on silica gel (PEIEA = 10/1 to 4/1) to afford compound(460 g, 75% yield) as a solid.1HNMR (400 MHz, DMSQd6): 7.68 (s, 1H), 7.07 (s 2H). MS Calcd.: 255 MS Found: 256 ([M+Hfl.

According to the analysis of related databases, 33332-28-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; H. LUNDBECK A/S; SVENSTRUP, Niels; WEN, Kate; WANG, Yazhou; (78 pag.)WO2017/5786; (2017); 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. 25513-93-3, name is 3-Methylpyrazine-2-carbaldehyde, A new synthetic method of this compound is introduced below., Recommanded Product: 3-Methylpyrazine-2-carbaldehyde

General procedure: Compound 1a-9a (1.0mmol) was dissolved in toluene (70mL) in a flask which was wrapped with tin foil, sodium hydride (1.5mmol) and triethyl phosphonoacetate (1.0mmol) was added respectively. Then the reaction solution was stirred at room temperature under dark until TLC analysis showed complete conversion. Extracted with EtOAc, the combined organic phase was washed with saturated brine (50mL×3), and dried over anhydrous sodium sulfate. Concentrated and purified by column chromatography (PE/EA=8: 1) to give a pale yellow solid (1b-9b). The synthetic routes are similar to PL [7,12].

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:
Article; Zou, Yu; Yan, Chang; Zhang, Huibin; Xu, Jinyi; Zhang, Dayong; Huang, Zhangjian; Zhang, Yihua; European Journal of Medicinal Chemistry; vol. 138; (2017); p. 313 – 319;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 939412-86-9, 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.

To a mixture of (3-chloropyrazin-2-yl)methanamine hydrochloride (3.9 g, 21.8 mmol, leq) and (S)-l-((benzyloxy)carbonyl)piperidine-2-carboxylic acid (5.73 g, 21.8 mmol, 1.0 eq) in DCM (50 mL), was added TEA (12.1 mL, 87.2 mmol, 4.0 eq). The reaction mixture was cooled to 0 C. After 10 min, HATU (9.94 g, 26.2 mmol, 1.2 eq) was added, and the reaction mixture was stirred at 0 C for 1 h and then at room temperature overnight. The mixture was washed subsequently with 0.1 M HCl-solution, 5% NaHC0 ; water and brine. It was dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by silica gel column chromatography (DCM/MeOH=200: l – 50: 1) to afford the desired product 1 (7.13 g, yield 84.4 %). LCMS: m/z = 389 [M+H]+.

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; LIAO, Xibin; SUZHOU BAIJIBUGONG PHARMACEUTICAL TECHNOLOGY CO. LTD.; LI, Jia; LU, Zhijian; ZHOU, Yubo; GAO, Anhui; (100 pag.)WO2018/175512; (2018); 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. 5049-61-6, name is Pyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of Pyrazin-2-amine

The mixture of aminopyrazine (3.0 g, 0.03316 mol) and 2-bromoethylpyruvate (4.77 mL, 0.0379 mol) in anhydrous ethanol (150 mL) was heated under continuous nitrogen flow at reflux for 6 hours. The reaction mixture was treated with charcoal (10 g), filtered through a CeliteNo. pad and concentrated under reduced pressure down to 25 mL. The solution was added dropwise to the saturated solution of sodium bicarbonate in water (300 mL) and the aqueous layer was extracted with DCM (3×200 mL). The combined organic extracts were dried with magnesium sulfate and concentrated. The residue was suspended in ether (40 mL) and the precipitate was collected by filtration and dried to yield imidazo[1,2-a]pyrazine-2- carboxylic acid ethyl ester (1.4 g, 0.0073 mol) as an off-white solid. m/z: (M + H)+ 192.

According to the analysis of related databases, 5049-61-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ABBOTT LABORATORIES; WO2005/110410; (2005); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 54608-52-5,Some common heterocyclic compound, 54608-52-5, name is 2-Hydrazinopyrazine, molecular formula is C4H6N4, 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: (+)-Usnic acid (1 equiv.) and hydrazines/hydrazides (1.1 equiv.) were added in absolute EtOH under nitrogen and the reaction mixture was stirred at 80C for 2h. For the hydrazines/hydrazides hydrochloride salt materials, they (1.1 equiv) were added to absolute ethanol, and an equivalent amount of pyridine (1.1 equiv) was added dropwise thereto and stirred at 80C under nitrogen. After 5min, (+) – usnic acid was added and the reaction mixture was stirred for another 2h. After reaction was complete, the reaction solution was cooled and concentrated under reduced pressure. The residues were quickly purified by silica gel column (PE/EtOAc).

The synthetic route of 54608-52-5 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Shi, Cun-Jian; Peng, Wan; Zhao, Jin-Hua; Yang, Hua-Li; Qu, Lai-Liang; Wang, Cheng; Kong, Ling-Yi; Wang, Xiao-Bing; European Journal of Medicinal Chemistry; vol. 187; (2020);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 16298-03-6, 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. 16298-03-6 name is Methyl 2-aminopyrazine-3-carboxylate, 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.

Reference Example 15 3-Iodopyrazine-2-carboxylic acid methyl ester (Reference compound No.15-1) Isoamyl nitrite (5.2 mL, 39 mmol) was added to a suspension of 3-aminopyrazine-2-carboxylic acid methyl ester (1.9 g, 12 mmol) in diiodomethane (20 mL) at 85C, then the mixture was stirred at 100C for 15 hours. The reaction mixture was allowed to stand and purified by silica gel column chromatography to give 1.4 g of the title reference compound as a pale yellow solid. (Yield 44%) 1H-NMR(500MHz,CDCl3) delta 4.04(s,3H),8.47(d,J = 2.1 Hz,1H),8.56(d,J = 2.1 Hz,1H)

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 2-aminopyrazine-3-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; SANTEN PHARMACEUTICAL CO., LTD.; EP1602647; (2005); 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. 19745-07-4, name is 2,5-Dichloropyrazine, A new synthetic method of this compound is introduced below., HPLC of Formula: C4H2Cl2N2

To a suspension of (S)-(2,2-dimethyl-l,3-dioxolan-4-yl)methanol (8.87 g, 67.1 mmol), in Nu,Nu-Dimethylformamide (DMF) (50 mL) stirred under nitrogen at 0C was added cesium carbonate (32.8 g, 101 mmol), the resulting reaction mixture was stirred at 0 C for 1 hr. To this added 2,5-dichloropyrazine (10 g, 67.1 mmol). The resulting reaction mixture was stirred at 100 C for 6 hr. Progress of the reaction was monitored by TLC. TLC indicated starting material was consumed to form new polar spot with 0.3 Rf. The reaction mass was cooled to rt, added water(lOOmL) and extracted with Ethyl acetate(lOOmL). The organic layer was washed with water(100mLX2). The organic layer was dried over Na2S04 and filtered and concentrated to get crude as light brown liquid. The crude product was added to a silica gel (60-120) column and was eluted with Hex/EtOAc. Collected fractions: 30%EtOAc in Hexane the product was eluted. Concentrated the product fractions to afford (S)-2-chloro-5-((2,2-dimethyl-l,3-dioxolan-4-yl)methoxy)pyrazine (12 g, 47.7 mmol, 71.0 % yield) as light brown liquid, LCMS (m/z): 244.90 [M+H]+.

The synthetic route of 19745-07-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; ELLIS, James Lamond; EVANS, Karen Anderson; FOX, Ryan Michael; MILLER, William Henry; SEEFELD, Mark Andrew; (766 pag.)WO2016/79709; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 36070-75-4, The chemical industry reduces the impact on the environment during synthesis 36070-75-4, name is 5-Chloropyrazine-2-carbonitrile, I believe this compound will play a more active role in future production and life.

The rac-I -((2S,3R,4R)-4-amino-2-ethyl-6-fluoro-3-methyl-3,4-dihyd roquinolin- I (2H )-yl)ethanone (forpreparation see Intermediate 40, 100 mg, 0.400 mmol), 5-chloropyrazine-2-carbonitrile (III mg,0.799 mmol), DIPEA (0.140 mL, 0.799 mmol) and N-methyl-2-pyrrolidone (NMP) (2 mL) were placeda microwaveable vial and irradiated in a microwave at 200 C for 2.5 h. The reactions purified directly using a MDAP (Formic) to give a solid, this solid was eluted through a NH2 SPE (5 g) with MeOH, the eluent was concentrated and dried to give the product (77 mg, 0.218 mmol, 54.5%) as an orange solid. LCMS (2 mm Formic): Rt = 0.93 mi [MH] = 354.

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

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; AMANS, Dominique; ATKINSON, Stephen John; HARRISON, Lee Andrew; HIRST, David Jonathan; LAW, Robert Peter; LINDON, Matthew; PRESTON, Alexander; SEAL, Jonathan Thomas; WELLAWAY, Christopher Roland; WO2014/140076; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

138588-41-7, name is Pyrazine-2-carboximidamide hydrochloride, 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. Recommanded Product: 138588-41-7

A mixture of 2-(2,4,6-trifluoro-phenyl)-malonic acid diethyl ester (200 g, 0.67 mol), pyrazine-2-carboxamidine hydrochloride (132 g, 0.828 mol) and potassium carbonate (114 g, 0.828 mol) in 2-methyoxyethyl ether (diglyme, 600 mL) is heated to 120 C. and stirred for 4 h, then heated to 140 C. and stirred for an additional 2 h. The mixture is cooled to room temperature (25-30 C.) and water (1200 mL) is added over about 15 min. Acetic acid (50 g) is added over 15 min. and 82 ml of concentrated HCl is added over 15 min and the mixture is stirred for about 15 min. at room temperature at a pH of about 2-3. The solid is filtered and washed with water (2×400 mL) and isopropyl alcohol (IPA) (400 mL) and dried at 60 C./10 mmHg for 24 h to give a white solid 69% yield with 95% HPLC purity. 1H NMR (DMSO-d6): d 12.45 (bs, 2H), 9.41 (s,1H), 8.91 (s,1H), 8.46 (m, 1 H), 7.23 (m, 2H).

The synthetic route of 138588-41-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Wyeth; US2006/281760; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem