Month: June 2021

Application of 16298-03-6, 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 16298-03-6 as follows.

Step 1a: Methyl 3-[(2,4-dimethoxybenzyl)amino]pyrazine-2-carboxylate Sodium triacetoxyborohydride (7.82 g, 36.89 mmol) was added to a mixture of methyl 3-aminopyrazine-2-carboxylate (4.00 g, 26.12 mmol) and 2,4-dimethoxybenzaldehyde (4.83 g, 29.04 mmol) in 1,2-dichloroethane (90 ml). The reaction was continued at room temperature for 24 hours. Sodium triacetoxyborohydride (13.0 g, 61.34 mmol) and 2,4-dimethoxybenzaldehyde (8.0 g, 48.14 mmol) were added and the reaction continued at room temperature over night. Water and DCM were added and the phases separated. The product was purified further by flash chromatography (SiO2, heptane:ethyl acetate, product came at 50percent ethyl acetate) and recrystallisation (DCM/heptane) to give a slightly yellow solid (5.00 g, 63percent). 1H NMR (400 MHz, CDCl3) delta 8.35-8.27 (br, 1H), 8.22 (d, 1H), 7.82 (d, 1H), 7.20 (d, 1H), 6.48-6.43 (m, 1H), 6.43-6.37 (m, 1H), 4.63 (d, 2H), 3.93 (s, 3H), 3.84 (s, 3H), 3.77 (s, 3H). MS m/z 304 (M+H)+.

According to the analysis of related databases, 16298-03-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Cheng, Leifeng; Jonforsen, Maria; Schell, Peter; US2009/88439; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 76537-18-3, A common heterocyclic compound, 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, molecular formula is C4H3BrClN3, 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.

3-Bromo-5-chloropyrazin-2-amine (200 mg, 0.96 mmol),Triethylamine (290 mg, 2.88 mmol), cuprous iodide(5mg, 0.33mmol)And bis(triphenylphosphine)palladium dichloride (13 mg, 0.02 mmol) was dissolved in tetrahydrofuran (5 mL).The reaction solution was stirred at room temperature.Then trimethylethynyl silicon (0.15 mL, 1.06 mmol)Slowly adding dropwise to the above reaction solution,After completion of the dropwise addition, the resulting reaction solution was heated to 55 C to continue the reaction for 1 hour.After the reaction system is cooled to room temperature,The reaction solution was diluted with ethyl acetate (50 mL).Filter and concentrate the filtrate under reduced pressure.The residue obtained was purified by silica gel column chromatography (PE/EA (v/v) = 30/1).The title compound was obtained as a pale yellow solid ( 208 g, 96%).

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; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Ren Qingyun; Tang Changhua; Yin Junjun; Yi Kai; Lei Yibo; Wang Yejun; Zhang Yingjun; Nie Biao; Xu Juan; Yan Huan; Chen Jianping; (90 pag.)CN108727369; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 109838-85-9, These common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, 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.

(S)-((2S,5R)-5-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazin-2-yl)(4-(trifluoromethyl)phenyl)methanol: To a mixture of (R)-2,5-dihydro-3,6-dimethoxy-2- isopropylpyrazine (5.2 tnL, 29 mmol)(commercially available from 3B Scientific Corporation Product List (Order Number 3B3-054672)) and THF (50 mL) at -78°C was added n-butyllithium (2.5 M solution in hexane, 12 mL, 31 mmol). The mixture was stirred for 15 minutes. The colorless solution turned light brown. A solution of 4- (trifluoromethyl)benzaldehyde (5.1 mL, 38 mmol)(commerciaHy available from 3B Scientific Corporation Product List (Order Number 3B4-3644)) in THF (50 mL) was added dropwise through a dropping funnel at -78°C. The mixture was stirred for 1 hour. The reaction mixture was diluted with EtOAc and washed with a mixed solution of aqueous Na2HPO4 and KH2PO4 solution (pH =8). The aqueous layer was extracted with EtOAc three times. The combined organic layers were washed with water and brine, dried over Na2SO4, and concentrated in vacuo. The crude residue was separated into two isomers by silica gel chromatography: 0-2percent- 10percent CH3CN-CH2CI2. The product was obtained as light yellow oil (2.3 g, 22 percent). LCMS (API-ES) m/z: 359 (M+H*).

The synthetic route of 109838-85-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMGEN INC.; WO2009/11871; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 54608-52-5, 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 54608-52-5 as follows.

Ethyl 1-benzyl-2,4-dioxopiperidine-3-carboxylate (58.5 mg, 0.21 mmol) in EtOH (2 mL) was added to a biotage microwave vial under nitrogen containing 2-hydrazinopyrazine (38.5 mg, 0.35 mmol) at RT. To this stirred reaction mixture was added AcOH (0.024 mL, 0.42 mmol) and then stirred at RT for 18 hours in a sealed microwave vial. The reaction was heated to 140 C for 10 hours in the microwave reactor and cooled to RT. The reaction mixture was evaporated in the Genevac and then redissolved in 2 ml DMSO, filtered and the crude product was purified by flash RP chromatography (35g Puriflash, 15mu, HC column), using decreasingly polar mixtures of water (containing 1% NH4OH) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 5-benzyl-2-(pyrazin-2-yl)-1,2,6,7-tetrahydro-3H-pyrazolo[4,3-c]pyridine-3,4(5H)-dione (14.6 mg, 19.2 %) as a white solid.

According to the analysis of related databases, 54608-52-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Fairley, Gary; Greenwood, Ryan; McMillan, Caroline Anne; Tetrahedron Letters; vol. 59; 39; (2018); p. 3574 – 3578;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 33332-28-4,Some common heterocyclic compound, 33332-28-4, name is 2-Amino-6-chloropyrazine, molecular formula is C4H4ClN3, 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.

[0504] Compound 481A was prepared by an analogous method as that of 473B, except using compound 2-chloro-6-aminopyrazine in place of compound 2-bromo-6-aminopyridine.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Amino-6-chloropyrazine, its application will become more common.

Reference:
Patent; Das, Jagabandhu; Padmanabha, Ramesh; Chen, Ping; Norris, Derek J.; Doweyko, Arthur M.P.; Barrish, Joel C.; Wityak, John; Lombardo, Louis J.; Lee, Francis Y.F.; US2004/54186; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 5049-61-6, These common heterocyclic compound, 5049-61-6, name is Pyrazin-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.

To a solution of 2-aminopyrazine (i) (2 g, 21.02 mmol) in dry DCM (10 ml) was added NBS (3.78 g, 21.23 mmol) portion-wise under cold condition and the resulting mixture was allowed to stir at RT for 6h. 5 ml of water was added and the layers were separated. Aqueous layer was extracted with DCM (10 ml X 2). Combined organic layers were washed with Brine solution (5 ml), dried over anhydrous Na2S04 and concentrated under vacuum. Crude material was purified by column chromatography over silica gel 230-400 mesh by using 18% of ethyl acetate in petroleum ether as an eluent to afford compound (ii) (1.98 g, 54.42%) as white solid.

The synthetic route of 5049-61-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UNIVERSITY OF CAPE TOWN; MMV MEDICINES FOR MALARIA VENTURE; YOUNIS, Yassir; CHIBALE, Kelly; WITTY, Michael, John; WATERSON, David; WO2013/121387; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 88625-24-5, 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. 88625-24-5 name is 5-Chloropyrazine-2-carbaldehyde, 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.

2) N,N-dimethylformamide (10 mL) was added to 5-chloropyrazine-2-carbaldehyde (500 mg), methyl 2,2-dimethyl-3-{[4-methyl-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan- 2-yl)pyridin-2-yl]oxy}propanoate (1410 mg) and 2N aqueous sodium carbonate solution (5.26 mL), and after replacing the atmosphere with nitrogen, palladium chloride (dppf) methylene chloride complex (143 mg) was added to the mixture and the resulting mixture was stirred at 65C for 2 hours. To the reaction mixture were added ethyl acetate and water, and the liquids were separated. After filtration with Celite, the organic layer was separated, washed with water and then with a saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane: ethyl acetate=100:0 to 70:30) to obtain methyl 3-{[5-(5-formylpyrazin-2-yl)-4-methylpyridin- 2-yl]oxy}-2,2-dimethylpropanoate (855 mg). MS (m/z): 330 [M+H]+

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

Reference:
Patent; MITSUBISHI TANABE PHARMA CORPORATION; SAKURAI, Osamu; SARUTA, Kunio; HAYASHI, Norimitsu; GOI, Takashi; MOROKUMA, Kenji; TSUJISHIMA, Hidekazu; SAWAMOTO, Hiroaki; SHITAMA, Hiroaki; IMASHIRO, Ritsuo; WO2012/81736; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 68774-77-6, name is 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine, belongs to pyrazines compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 68774-77-6, Safety of 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine

A mixture of crude 4-methylbenzyl 4-(aminomethyl)-3,3-difluoropiperidine-1-carboxylate (600mg, 2.0 mmol), 8-chloro-[1,2,4]triazolo[4,3-a]pyrazine (360 mg, 2.0 mmol) and DIPEA (0.76 mL, 4.0 mmol) in butyl alcohol (10 mL) was heated at 130 C overnight. The mixture was allowed to cool to room temperature and concentrated under reduced pressure. The concentrate was purified by column chromatography over silica gel (100% ethyl acetate) to afford the title compound as a light gray powder (150 mg, 18%). MS (ESI) calcd for C20H22F2N602: 416.2; found: 417.3 [M+H]. 1H NMR (400MHz, CD3OD) 6 9.16 (s, 1H), 7.77 (d, J = 4.8 Hz, 1H), 7.29 (d, J = 4.8 Hz, 1H), 7.24 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 5.09 (s, 2H), 4.33 (br s, 1H), 4.19-4.15 (m, 1H), 4.05-3.95 (m, 1H), 3.72-3.58 (m, 1H), 3.25-2.90 (m, 2H), 2.67-2.51 (m,1H), 2.33 (s, 3H), 1.99-1.93 (m, 1H), 1.62-1.52 (m, 1H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine, and friends who are interested can also refer to it.

Reference:
Patent; RUGEN HOLDINGS (CAYMAN) LIMITED; SHAPIRO, Gideon; (246 pag.)WO2016/196513; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 1196152-38-1, A common heterocyclic compound, 1196152-38-1, name is 2-Bromo-5-(trifluoromethyl)pyrazine, molecular formula is C5H2BrF3N2, 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.

Example 81N- (3,4-Dif [uoropheny[)-3-methy[-5-{[5- (trif[uoromethy[)pyrazin-2-y[]amino- 1 ,2-thiazo[e-4-carboxamide A mixture of 5-amino-N-(3,4-dif[uoropheny[)-3-methy[-1 ,2-thiazo[e-4-carboxamide [Intermediate 3] (100 mg, 0.37 mmo[, 1.0 eq), 2-bromo-5-(trif[uoromethy[)- pyrazine [CAS-RN: 1196152-38-1] (105 mg, 0.45 mmo[, 1.2 eq) and cesiumcarbonate (242 mg, 0.74 mmo[, 2.0 eq) in 4.0 mL dioxane/DMF (7/1) was p[aced ina microwave via[ that was f[ushed with argon. Then, pa[[adium(II) acetate (8 mg,0.04 mmo[, 0.1 eq) and Xantphos (21 mg, 0.04 mmo[, 0.1 eq) were added.Afterwards, the via[ was sea[ed and the reaction mixture was stirred at anenvironmenta[ temperature of 110 C for 4 h. On coo[ing, the reaction mixture was partitioned between ethy[ acetate and water. The organic phase was washed with brine and the phases were separated by the use of a Whatman fi[ter. The vo[ati[e components of the organic phase were removed in vacuo. Purification was conducted via preparative HPLC (Method A) to give 36 mg (22 % yie[d of theory) ofthe tit[e compound.UPLC-MS (Method 1): Rt = 1.36 mm; MS (ESIneg) m/z = 414 [M-H].1HNMR (400 MHz, DMSO-d6): oe [ppm] = 2.46 (s, 3H), 7.34-7.54 (m, 2H), 7.95 (dd, 1H), 8.82 (s, 1H), 8.91 (s, 1H), 10.53 (s, 1H), 11.46 (s, 1H).

The synthetic route of 1196152-38-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BAeRFACKER, Lars; PRECHTL, Stefan; SIEMEISTER, Gerhard; WENGNER, Antje Margret; ACKERSTAFF, Jens; NOWAK-REPPEL, Katrin; BADER, Benjamin; LIENAU, Philip; STOeCKIGT, Detlef; WO2014/118186; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, 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. Safety of Methyl 3-amino-6-bromopyrazine-2-carboxylate

Step 1 : 3-amino-6-bromo-N-methylpyrazine-2-carboxamide[00261] Methyl 3-amino-6-bromo-pyrazine-2-carboxylate (7.5 g, 32.32 mmol) was suspended in 40% aqueous methylamine and the resulting mixture stirred vigorously at RT for 4 hours. The resultant precipitate was collected, washed with water and dried to give the desired product(6.73g, 90% Yield). IH NMR (400.0MHz, DMSO) d 2.76 (s, 3H), 7.75 (br s, 2H), 8.34 (s, IH),8.58 (b rs, IH) ppm; MS (ES+) 232.

The synthetic route of 6966-01-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-damien; DURRANT, Steven; KAY, David; O’DONNELL, Michael; KNEGTEL, Ronald; MACCORMICK, Somhairle; PINDER, Joanne; VIRANI, Anisa; YOUNG, Stephen; BINCH, Hayley; CLEVELAND, Thomas; FANNING, Lev, T.d.; HURLEY, Dennis; JOSHI, Pramod; SHETH, Urvi; SILINA, Alina; WO2010/54398; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem