Category: Pyrazines

Electric Literature of 33332-29-5, The chemical industry reduces the impact on the environment during synthesis 33332-29-5, name is 2-Amino-5-chloropyrazine, I believe this compound will play a more active role in future production and life.

Intermediate 22 5-Methoxypyrazin-2-amine [0242] To a solution of 5-chloropyrazin-2-amine (0.2 g, 1.54 mmol) in MeOH (3 mL) was added Cu powder (0.13 g, 2.07 mmol), followed by a solution of sodium methoxide in MeOH (0.38 mL, 1.75 mmol). The reaction mixture was stirred at 150 C. in a sealed tube for 24 h. The reaction mixture was then filtered through Celite, and the filtrate was concentrated in vacuo. The crude product obtained was purified by column chromatography (silica: 100-200 mesh, MeOH: DCM 2-3%) to afford the title compound (0.13 g, 67%). LCMS (ES+) 126 (M+H)+, RT 1.06 minutes (method 1).

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

Reference:
Patent; Brookings, Daniel Christopher; Ford, Daniel James; Franklin, Richard Jeremy; Ghawalkar, Anant Ramrao; Kulisa, Claire Louise; Neuss, Judi Charlotte; Reuberson, James Thomas; US2014/315885; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 59489-71-3,Some common heterocyclic compound, 59489-71-3, name is 2-Amino-5-bromopyrazine, molecular formula is C4H4BrN3, 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. 5-vinylpyrazin-2-amine; To a mixture of 5-bromopyrazin-2-amine (1.0 g, 5.78 mmol) and vinyltri-n-butyltin (2.01 g, 6.36 mmol) in DMF(19 mL) were added LiCl (269 mg, 6.36 mmol) and DIEA (1.1 mL, 6.36 mmol). After degassing for 20 minutes, Pd(PPh3)4 (400 mg, 0.35mmol) was added to the reaction mixture. And then the mixture was refluxed for 4 hours under Ar atmosphere. The reaction mixture was cooled to room temperature and stirred with a 10% aqueous solution of potassium fluoride for 1 hour. The resulting solution was filtered through a pad of celite and washed with ethyl acetated. The aqueous layer was separated and extracted with ethyl acetate. The combined organic layer was dried over MgS04 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (30% to 50% Ethyl acetate/Hexane) to afford title product (540 mg, 77% yield). MS m/z : 122 [M+l].

The synthetic route of 59489-71-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; DANA-FARBER CANCER INSTITUTE, INC.; GRAY, Nathanael, S.; WO2011/90738; (2011); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 27398-39-6, name is 3-Chloropyrazine-2-carboxylic acid, 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 27398-39-6, category: Pyrazines

3-4) To a solution of 2-chloropyrazine-3-carboxylic acid (0.15 g, 1.0 mmol), 1-[1-(2,4-dichlorophenyl)cyclopropyl]ethylamine hydrochloride (0.25 g, 0.94 mmol) and 4-dimethylaminopyridine (0.29 g, 2.4 mmol) in chloroform (10 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.22 g, 1.2 mmol) and the mixture was stirred at room temperature for 12 hrs. After adding water and chloroform, the mixture was separated, and the organic layer was washed successively with water and saturated brine and dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1) to give a desired compound (yield; 0.24 g, 69percent). property; 1H-NMR [CDCl3/TMS,delta value (ppm)]: 8.53(d, 1H), 8.47(d, 1H), 7.55(br, 1H), 7.37(d, 1H), 7.32(d, 1H), 7.19(dd, 1H), 4.11(m, 1H), 1.28(m, 1H),1.23(d, 3H), 1.01(m, 1H), 0.90(m, 2H)

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; NIHON NOHYAKU CO., LTD.; EP1997800; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, 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. Quality Control of 5-Aminopyrazine-2-carbonitrile

Example 13 2-({[2-(2-methylbiphenyl-3-yl)imidazo[l,2-a]pyrazin-6-yl]methyl}amino)ethanol Stepl : 2-( 2-methylbiphenyl itrile To a solution of 2-bromo-l-(2-methylbiphenyl-3-yl)ethanone (Example 5, Step 2: Til mg, 2.71 mmol) in isopropyl alcohol (10 mL) was added 5-aminopyrazine-2-carbonitrile (Ark Pharm, catAK-21935: 325. mg, 2.71 mmol). The resulting mixture was heated at 110 C overnight then cooled to room temperature and concentrated. The residue was purified by flash chromatography on a silica gel column eluting with 0 to 25 % ethyl acetate/DCM to give the desired product. LC-MS calculated for C20H15N4 (M+H)+: m/z = 311.1 ; found 311.1.

The synthetic route of 113305-94-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; INCYTE CORPORATION; WU, Liangxing; SHEN, Bo; LI, Jingwei; LI, Zhenwu; LIU, Kai; ZHANG, Fenglei; YAO, Wenqing; (120 pag.)WO2017/70089; (2017); 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 1082843-72-8 as follows. Quality Control of 6-Bromo-3-chloropyrazin-2-amine

General procedure: Sodium ethanethiolate (1.85 g, 21.95 mmol) was added to a solution of 4,6-dichloropyrimidin-5-amine (3.00 g, 18.29mmol) in methanol(100 mL) and heated at reflux for 3 hours. The reactionmixture was evaporated to dryness and redissolved in EtOAc (50 mL) and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic phase was dried over MgSO4, filtered and evaporated toafford the crudeproduct. The crude product was purified by flash silica chromatography, elutiongradient 5% to 25% EtOAc in heptane. Pure fractions were evaporated to drynessto afford 4-chloro-6-(ethylthio)pyrimidin-5-amine (2.70 g, 78%) as a white solid;

According to the analysis of related databases, 1082843-72-8, the application of this compound in the production field has become more and more popular.

Reference:
Article; Boyd, Scott; Davies, Robert D.M.; Degorce, Sebastien L.; Groombridge, Sam; S. Scott, James; Stokes, Stephen; Tetrahedron Letters; vol. 57; 1; (2016); p. 152 – 154;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 27398-39-6,Some common heterocyclic compound, 27398-39-6, name is 3-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.

To a solution of 3-ehioropyrazine-2-earboxyiic acid (100 rng, 0,63 mmoi) in DCM/MeOH (2 mL: 0.2 mL) was added TMSCHN2 (0.47 rnL, 0.95 mrnoi) at RI and theresulting mixture stirred at RT for 2 h. Acetic acid (0.2 mL) was added and the mixture diluted with water (2 mL) and extracted with DCM (4 mL x 3). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give the title compound as a oil. LRMS m/z (M+H) 173.0 found, 173.0 required.

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-carboxylic acid, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; KUDUK, Scott D.; LIVERTON, Nigel; LUO, Yunfu; SKUDLAREK, Jason; (79 pag.)WO2016/95204; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 14508-49-7, name is 2-Chloropyrazine, 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. SDS of cas: 14508-49-7

General procedure: A 10 mL round-bottom flask was charged with the prescribedamount of catalyst Pd/Cu, aryl chlorides (0.5 mmol), phenylboronicacids containing hydroxymethyl (0.75 mmol), Cs2CO3 (1.0 mmol)and dioxane (5 mL) in air. The reaction mixture was then placedin an oil bath and heated at 110 C for 24 h. After removal of thesolvent, the resulting residue was purified by flash chromatographyon silica gel using CH2Cl2 as eluent. The products 4a-k, and4m are known compounds [6,9] except for 4l and 4n.

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

Reference:
Article; Xu, Chen; Li, Hong-Mei; Wang, Zhi-Qiang; Fu, Wei-Jun; Inorganica Chimica Acta; vol. 423; 1; (2014); p. 11 – 15;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 622392-04-5, name is 2-Bromo-5-iodopyrazine, 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. category: Pyrazines

2-Bromo-5-iodopyrazine [CAS RN: 622392-04-5] (3.50 g, 12.3 mmol, 1.0 eq),4,4,5,5-tetramethyl-2-(prop-1 -en-2-yl)-1 ,3,2-dioxaborolane [CAS RN: 126726-62-3] (3.10 g, 18.4 mmo[, 1.5 eq), Pd(dppf)C[2.CH2C[2 (502 mg, 0.61 mmo[, 0.05 eq) and cesium carbonate (12.0 g, 36.9 mmo[, 3.0 eq) were dissolved in 130 mL dioxane/water (5/1). The reaction mixture was heated to 90C for 2 h. On cooling, the reaction mixture was partitioned between water anddichloromethane. The organic phase was washed with brine and the phases were separated by the use of a Whatman filter. The volatile components were removed in vacuo and the crude material was purified via preparative MPLC (Biotage Isolera; 100 g SNAP cartridge: hexane -> hexane/ethyl acetate 9/1) to give 600 mg (25% yield of theory) of the title compound in a round 50% purity(UPLC-area%). The impurity was identified as 2,5-di(prop-1-en-2-yl)pyrazine, that was not expected to interfere in the subsequent reaction step. The material obtained was used without further purification.UPLC-MS (Method 4): R = 1.18 mm; MS (ESI0): m/z = 199 [M].

The synthetic route of 2-Bromo-5-iodopyrazine has been constantly updated, and we look forward to future research findings.

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

These common heterocyclic compound, 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, 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. HPLC of Formula: C6H7F3N4

VI (2.0g, 5.0mmol) and 3- (trifluoromethyl) -5,6,7,8-tetrahydro – [1,2,4] triazolo [4,3-a] pyrazine (of 0.912 g , 4.7mmol) Was dissolved in 20ml of anhydrous N, N- dimethylformamide was added HOBt (0.770g, 5.7mmol) and EDC ¡¤ HCl (1.092g, 5.7mmol), stirred at room temperature 20h. After the reaction was added 20ml of water and 20ml of ethyl acetate, there Phase was washed with water 3 times, washed three times with saturated aqueous sodium carbonate solution, the organic phase was dried over anhydrous sodium sulfate, suction filtered, and concentrated to give yellow Colored foamy solid 2.967g, crude yield> 100%, recrystallized from ethyl acetate, filtration and drying to give a yellow solid 1.827g, Recrystallization yield of 63.6%.

The synthetic route of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shanghai Institute Of Pharmaceutical Industry; China State Institute of Pharmaceutical Industry; Meng, Xiangguo; Cai, Zhengyan; Zhou, Weicheng; Jiang, Jingzhang; Zhu, Yijun; Ge, Yuanyuan; Yan, Pingping; (32 pag.)CN103172635; (2016); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 313339-92-3, name is 3,5-Dichloropyrazine-2-carbonitrile, 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 313339-92-3, SDS of cas: 313339-92-3

[00229] Step 1 : To a mixture of 3,5-dichloropyrazine-2-carbonitrile (68 mg, 0.39 mmol) in 2-methylpropan-2-ol (2 mL) was added tert-butyl l-amino-3-(methylthio)propan-2- ylcarbamate (50 mg, 0.23 mmol), Hunig’s base (101 mg, 0.780 mmol) under N2. The mixture was heated to 50 C under a 2 atmosphere for 5 hours. Upon cooling to 25 C, the mixture was diluted with brine (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organics were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (1: 1 petroleum ether/EtOAc) to afford tert-butyl l-(6-chloro- 5-cyanopyrazin-2-ylamino)-3-(methylthio)propan-2-ylcarbamate as a solid. MS ESI calc’d. for Ci4H21ClN502S [M + H]+ 358, found 358. XH NMR (400MHz, DMSO-d6) delta 7.80 (s, 1H), 6.84 (s, 1H), 5.06 (s, 1H), 3.99 – 3.93 (m, 1H), 3.64 – 3.51 (m, 2H), 2.68 – 2.67 (m, 2H), 2.13 (s, 3H), 1.38 (s, 9H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,5-Dichloropyrazine-2-carbonitrile, and friends who are interested can also refer to it.

Reference:
Patent; MERCK SHARP & DOHME CORP.; ALTMAN, Michael, D.; CASH, Brandon; ELLIS, John Michael; MADDESS, Matthew, L.; NORTHRUP, Alan, B.; OTTE, Ryan, D.; SUN, Binyuan; WO2015/138273; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem