Month: September 2021

Some common heterocyclic compound, 91476-80-1, name is 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine, molecular formula is C6H9N3, 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. SDS of cas: 91476-80-1

6-chloro-2-(l,l-dimethylethyl)-l,3-benzoxazole-7-sulfonyl chloride (457 mg) was dissolved in 2.5 mL DCM and the solution was cooled to 0 0C. Triethylamine (0.41 mL) was added followed by 5,6,7,8-tetrahydroimidazo[l,2-alpha]pyrazine (201 mg) dissolved in 2.5 mL DCM. The reaction mixture was stirred at 0 0C to room temperature over night. The reaction was quenched with water and extracted with DCM (3×10 mL). The combined organic layers were dried Na2SOzI, filtered and the solvent was removed in vacuo. The crude product was purified by column chromatography eluting with a gradient of 0 to 20% MeOH in DCM yielding 409 mg of product. Rf: 0.57 (10% MeOH in DCM).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 91476-80-1, its application will become more common.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2007/124423; (2007); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 25911-65-3, name is 3-Aminopyrazine-2-carbonitrile, molecular formula is C5H4N4, 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: C5H4N4

EXAMPLE 4 Synthesis of 3-Amino-6-bromopyrazine-2-carbonitrile (Intermediate 3) To a solution of intermediate 2 (1.7 g, 14 mmol) in acetic acid (40 mL) at RT was added bromine (0.95 mL, 19 mmol) slowly. The resulting mixture was heated at 60 C. for 30 min and then cooled to RT. The mixture was poured into ice water and the resulting solid filtered. After thoroughly washed with water, the title compound was obtained as a yellow solid (2.3 g, 83%). 1H NMR (500 MHz, DMSO-d6): delta 8.44 (s, 1H), 7.60 (br s, 2H). MS (ES+): m/z 199 (M+H)+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 25911-65-3, its application will become more common.

Reference:
Patent; TargeGen, Inc.; US2007/259876; (2007); 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. 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, A new synthetic method of this compound is introduced below., SDS of cas: 5521-55-1

A solution of compound 4-6 (0.2 g, 0.3 mmol) in EtOAc (2 mL) was cooled to 0 C, and a solution of HC1 in EtOAc (3 0%, 2 mL) was added. The mixture was stirred at rt until no more gas evolution. The mixture was filtered to afford compound 4-7 as a white solid; the solid was washed with EtOAc (20 mL). A round-bottom flask was charged with compound 4-7, compound 9-1 (0.06 g, 0.4 mmol), EDCI (0.13 g, 0.66 mmol) and HOAT (0.1 g, 0.7 mmol), and then DCM (10 mL) was added under N2. The mixture was cooled to 0 C, and DIPEA (0.2 mL, 1 mmol) was added slowly. After the addition, the resulting mixture was stirred at 30 C for 6 hours. After the reaction was complete, the mixture was quenched with water (10 mL). The resulting mixture was extracted with DCM (10 mL) twice. The combined organic layers were washed with saturated aqueous NaC1 (10 mL) and dried over anhydrous Na2SO4, and then concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with PE : EtOAc (V:V)= 2:1 to give compound 9-2 (0.180 g, 80%) as a white solid. MS (ESI, pos.ion) m/z: 885.3[M+1] and 1HNIVIR (600 IVIHz, CDC13): 5 10.38 (s, 1H), 9.07 (d, J= 0.8 Hz, 1H), 8.44 (s, 1H), 8.15 (d, J= 6.7 Hz, 1H), 7.85 (d, J= 9.1 Hz, 2H), 7.47 (s, 1H), 7.04 (s, 1H), 6.95 (d, J 9.2 Hz, 1H),5.73 (dd, J= 18.2, 8.7 Hz, 1H), 5.50 (s, 1H), 5.02-4.97 (m, 1H), 4.69-4.64 (m, 2H), 4.49 (d, J= 11.5 Hz, 1H), 4.10 (dd, J = 11.6, 3.9 Hz, 1H), 3.77 (s, 3H), 3.22 (dt, J = 13.7, 6.8 Hz, 1H),2.92-2.86 (m, 1H), 2.71 (dd, J= 13.8, 7.7 Hz, 1H), 2.65 (s, 3H), 2.60 (s, 4H), 2.29-2.25 (m, 1H),2.04-2.00 (m, 1H), 1.91 (dd, J= 7.8, 6.1 Hz, 2H), 1.78-1.71 (m, 1H), 1.66 (dd, J= 9.4, 5.9 Hz,1H), 1.53-1.45 (m, 5H), 1.39 (t, J= 13.5 Hz, 7H), 1.16-1.07 (m, 3H), 0.94-0.86 (m, 2H) ppm.

The synthetic route of 5521-55-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; ZHANG, Yingjun; LUO, Huichao; REN, Qingyun; XIONG, Zhimin; LIU, Yang; LEI, Yibo; XIONG, Jinfeng; ZHANG, Jiancun; (123 pag.)WO2016/127859; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 1458-18-0,Some common heterocyclic compound, 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, molecular formula is C6H5Cl2N3O2, 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: To a solution of methyl 3-amino-5,6-dichloro-2-pyrazinecarboxylate (1.0 eq.) in 2-propanol (5 mL/mmol), an appropriate primary or secondary amine(3-6 eq.) was added, and the reaction mixture wasrefluxed for 2 h.10) The solution was cooled to roomtemperature, concentrated under reduced pressure, andthe residue was purified by silica-gel column chromatography(Wako gel C-200, 30-40% ethyl acetate/n-hexane) to afford the series 1 intermediate (yield:32-95%). The regioselectivity of the nucleophilicsubstitution at the 5-position of the pyrazine ring wasconfirmed by an X-ray structural analysis (Fig. S1).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, its application will become more common.

Reference:
Article; Murai, Masatoshi; Habu, Sayako; Murakami, Sonomi; Ito, Takeshi; Miyoshi, Hideto; Bioscience, Biotechnology and Biochemistry; vol. 79; 7; (2015); p. 1061 – 1066;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 486424-37-7, 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. 486424-37-7 name is 3-Amino-6-bromopyrazine-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.

To the 3L into the reaction bottle 50.1g II, 2L methanol. 0 – 5 C lower, to the slowly dropping 133g 98.3% concentrated sulfuric acid, then completing, heating up to 40 C, instead on invitation 48h to raw material II basic reaction end. turns on lathe does methanol, 0 – 5 C lower, adding 200 ml methanol, 500g ice water mixture, wherein the aqueous solution of sodium bicarbonate to pH=6 – 7 adds by drops full and adjusted to. Filtering, the filter cake 45 C vacuum drying 12h, get 43.2g brown solid III, yield 80.1%

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Amino-6-bromopyrazine-2-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; Nanjing Huawei Pharmaceutical Development Co., Ltd.; Bao Jinyuan; Huang Hui; Jiang Yuwei; Zhang Xiaoqing; (8 pag.)CN104496917; (2017); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 153800-11-4, 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. 153800-11-4 name is 2-Ethynylpyrazine, 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.

To a stirred solution of alkyne precursor 8b-16b (1.2 equiv) in THF was added dropwise a 1.0 M solution of TBAF in THF (1.44 equiv). The reaction mixture was stirred at room temperature for about 15 min. TLC analysis showed complete conversion of starting material to a major product (the de-silylation intermediate was slightly more polar than the alkyne precursor). The glycosyl azide (1.0 equiv), and 1:1 tert-butyl alcohol-water were then added to the above solution. A solution of sodium ascorbate (0.4 equiv) in water, followed by CuSO4 (0.2 equiv) in water, was successively added. The bright-yellow suspension was stirred vigorously at room temperature overnight. TLC analysis showed complete conversion of the starting material to a major product. The mixture was evaporated under reduced pressure, and the resultant residue was purified by flash chromatography to yield pure material.

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

Reference:
Article; Li, Tiehai; Guo, Lina; Zhang, Yan; Wang, Jiajia; Li, Zhonghua; Lin, Lin; Zhang, Zhenxing; Li, Lei; Lin, Jianping; Zhao, Wei; Li, Jing; Wang, Peng George; Carbohydrate Research; vol. 346; 9; (2011); p. 1083 – 1092;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature 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.

Dissolve 5-chloropyrazine-2-carboxylic acid (2.00 g, 12.62 mmol) in methylene chloride (30 mL) and at room temperature diisopropylethylamine (6.79 g, 39.74 mmol), 2,2,2-trifluoro Ethylamine (1.31 g, 13.24 mmol), O- (7-Azabenzotriazol-1-yl) -N, N, N ‘, N’-tetramethyluronium hexafluorophosphate (5.04 g, 13.24 mmol) is added,Stir at room temperature overnight.Saturated aqueous sodium carbonate was added, and the mixture was extracted twice with ethyl acetate and washed once with saturated brine.The extracted ethyl acetate layer was dried over anhydrous magnesium sulfate and filtered, and then ethyl acetate was evaporated under reduced pressure with an evaporator.The resulting crude product is purified by silica gel chromatography to give 5-chloro-N- (2,2,2-trifluoroethyl) pyrazine-2-Carboxamide (2.97 g, 98.9%, as a pale yellow oil) was obtained.

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; Nippon Kayaku; Ueno, Shotaro; Hasegawa, Shinji; Atarashi, Daiju; Kobayashi, Takeshi; Miyake, Takaaki; Asano, Shou; Sumi, Takuto; (116 pag.)JP2019/94290; (2019); A;,
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. 912773-21-8, name is 2-Bromo-5-chloropyrazine, A new synthetic method of this compound is introduced below., COA of Formula: C4H2BrClN2

Intermediate C-3 2-chloro-5-((2-(trifluoromethyl)pyridin-3-yl)thio)pyrazine A mixture of 2-(trifluoromethyl)pyridine-3-thiol (100 mg, 0.558 mmol), 2- bromo-5-chloro-pyrazine (195 mu, 0.670 mmol), Pd2(dba)3 (12.8 mg, 0.014 mmol), XantPhos (17.8 mg, 0.031 mmol), and DIPEA (144 mg, 1.12 mmol) in dioxane (degassed, 2.79 n L) was stirred for 2.5 h at 120 C. After cooling to RT, the reaction mixture was filtered through a pad of Celite followed by EtOAc (10 mL) wash. The combined filtrates were concentrated under reduced pressure and the resulting residue was purified by silica chromatography (0 to 25% gradient of EtO Ac/heptane) to give 2-chloro-5-((2-(trifluoromethyl)pyridin-3-yl)thio)pyrazine (252 mg, 0.864 mmol) as a brown oil. NMR (400 MHz, Chloroform- ) delta ppm 8.68 (dd, 7=4.7, 1.5 Hz, 1 H), 8.25 (d, 7=1.5 Hz, 1 H), 8.18 (d, 7=1.5 Hz, 1 H), 7.98 (dd, 7=8.1, 1.5 Hz, 1 H), 7.49 (dd, 7=8.0, 4.7 Hz, 1 H). MS m/z 292.0 (M+H)+.

The synthetic route of 912773-21-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; CHEN, Zhuoliang; FORTANET, Jorge Farcia; JOUK, Andriana; KARKI, Rajesh; LAMARCHE, Matthew J.; LIU, Gang; PALERMO, Mark G.; PEREZ, Lawrence Blas; SARVER, Patrick James; SHULTZ, Michael David; SENDZIK, Martin; TOURE, Bakary-Barry; YU, Bing; (173 pag.)WO2016/203406; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 120984-76-1, These common heterocyclic compound, 120984-76-1, name is 2-Bromo-3-methylpyrazine, 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.

2-Bromo-3-methylpyrazine (104 mg, 0.600 mmol),tetrakis(triphenylphosphine)palladium(0) (95%, 133 mg, 0.109 mmol) and sodium carbonate(175 mg, 1.64 mmol) were combined with 4-[3-methoxy-4-(4,4,5,5-tetramethyl-1 3,2-dioxaborolan-2-yl)phenoxy]furo[3 ,2-c]pyridine [Cl 0, which was prepared in analogous fashion to4-[3-methyl-4-(4 ,4,5,5-tetramethyl-1 ,3 ,2-dioxaborolan-2-yl)phenoxy]furo[3,2-c]pyrid me (C2) inExample 1] (200 mg, 0.545 mmol) in 1,4-dioxane (3 mL) and water (1 mL). The reaction mixturewas heated to 13000 in a microwave reactor for 1 hour. The mixture was cooled to roomtemperature, and the supernatant was decanted into another flask. The remaining solids were washed with ethyl acetate (3 x 10 mL) and the combined organic portions were concentrated in vacuo. Purification was carried out twice using silica gel chromatography (First column: Eluent:2% methanol in dichloromethane; Second column: Gradient: 0% to 100% ethyl acetate inheptane). The colorless fractions were combined and concentrated under reduced pressure to provide the product as a white solid. Yield: 85 mg, 0.25 mmol, 46%. LCMS m/z 334.0 (M+H). 1H NMR (400 MHz, CDCl3) oe 8.47 (AB quartet, downfield doublet is broadened, JAB=2.S Hz, AVAB=l4 Hz, 2H), 8.08 (d, J=5.9 Hz, 1H), 7.66 (d, J=2.3 Hz, 1H), 7.36 (d, J8.0 Hz, 1H), 7.25- 7.28 (m, 1H, assumed; partially obscured by solvent peak), 6.90-6.96 (m, 2H), 6.88 (dd, J=2.2,0.8 Hz, 1H), 3.79 (s, 3H), 2.50 (s, 3H). Yellow fractions were repurified to provide additional product: 55 mg, overall yield: 75%.

Statistics shows that 2-Bromo-3-methylpyrazine is playing an increasingly important role. we look forward to future research findings about 120984-76-1.

Reference:
Patent; PFIZER INC.; COE, Jotham, Wadsworth; ALLEN, John, Arthur; DAVOREN, Jennifer, Elizabeth; DOUNAY, Amy, Beth; EFREMOV, Ivan, Viktorovich; GRAY, David, Lawrence, Firman; GUILMETTE, Edward, Raymond; HARRIS, Anthony, Richard; HELAL, Christopher, John; HENDERSON, Jaclyn, Louise; MENTE, Scot, Richard; NASON, Deane, Milford, II; O’NEIL, Steven, Victor; SUBRAMANYAM, Chakrapani; XU, Wenjian; WO2014/72881; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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, 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. name: (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

To 30 ml of degassed triflouroethanol (TFE) were added Ruthenium(II) chloride 1,5-cyclooctadiene complex (18.2 mg, 0.037 mmol) and (R )-(-)-H(S)-2- Diphenylphosphino)ferrocenyl]ethyl di-tert-butylphosphine (44.8 mg, 0.083 mmol). The solution was degassed again, and left to stir at room temperature for 1 hour. To 250 ml glass reactor were added (Z)-3-amino-l-(3-(trifluoromethyl)-5,6-dihydro- [l,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)but-2-en-l-one (30 g, 74.07 mmol) and 100 ml TFE. The slurry was stirred and washed three times with N2. Than, the catalyst solution was added and the mixture washed three times with N2, then switched to H2 and washed three times. The H2 pressure was set to constant pressure of 5 bar and the reaction was heated to 55C for 23 hours. The TFE solution (93.3% purity and 77% R) was evaporated to yield oily-STG-base.

The synthetic route of 767340-03-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2009/70314; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem