Month: February 2021

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. 912773-24-1, name is 6-Bromoimidazo[1,2-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Formula: C6H4BrN3

General procedure: [0204] A suspension of 6-bromoimidazo[1,2-a]pyrazine 16* (13 mmol), a boronic acid (14 mmol) and potassium carbonate(42 mmol) in dioxane (40 mL) plus water (5 mL) was stirred under nitrogen for 10 minutes. (dppf)PdCl2 (1.3mmol) was added and the resulting suspension was stirred at 90 C for 2.5 hours. The reaction mixture was evaporatedunder reduced pressure and the residue was partitioned between dichloromethane and water, the organic phase wasseparated and evaporated under reduced pressure. The crude product was purified by flash chromatography to givethe intermediate 19.

According to the analysis of related databases, 912773-24-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Max-Planck-Gesellschaft zur Foerderung der Wissenschaften e.V.; Ullrich, Axel; Falcenberg, Mathias; EP2818471; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 870787-06-7, The chemical industry reduces the impact on the environment during synthesis 870787-06-7, name is 3-(Trifluoromethyl)pyrazine-2-carboxylic acid, I believe this compound will play a more active role in future production and life.

Example 17. Production of N-{3-isobutyl-4-[2,2,2-trifluoro-1-(trifluoromethyl)ethyl]pheny}-3-trifluoromethylpyrazine-2-carboxamide (compound No. 1-42) 3-Trifluoromethyl-2-pyrazine carboxylic acid (192 mg, 1 mmol), 3-isobutyl-4-[2,2,2-trifluoro-1-(trifluoromethyl)ethyl]aniline (199 mg, 1 mmol), 2-chloro-1-methylpyridinium iodide (255 mg, 1 mmol) and triethylamine (303 mg, 3 mmol) were dissolved in THF (10 ml) and refluxed under heating for 2 hours. The reaction solution was diluted with ethyl acetate, followed by washing with water. The organic layer was dried over magnesium sulfate anhydride, and concentrated under reduced pressure, and then the solution was purified by using silica gel chromatography (hexane:ethyl acetate=2:1) to obtain 293 mg of the desired compound as paste state. Yield: 62% Property: nD 1.4825 (27.7C)

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, 3-(Trifluoromethyl)pyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NIHON NOHYAKU CO., LTD.; EP1757595; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 912773-21-8,Some common heterocyclic compound, 912773-21-8, name is 2-Bromo-5-chloropyrazine, molecular formula is C4H2BrClN2, 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 suspension of copper (0) powder (244 g, 3877 mmol) in DMSO (5 L) was added ethyl 2-bromo-2,2-difluoroacetate (394 g, 1939 mmol) at RT. The reaction mixture was stirred at RT for 1 h and 2-bromo-5-chloropyrazine (Shanghai Fchemicals Technology Co., Ltd., Shanghai, China) (250 g, 1292 mmol) was added in portion-wise manner. The reaction mixture was stirred at RT for 3 h, and quenched with sat’d solution of ammonium chloride (2.0 L). The mixture was filtered through a celite pad and the filtrate was extracted with ethyl acetate (2 x 2 L). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0 – 2% ethyl acetate in hexanes) to afford 11a (215 g, 70% yield) as a viscous colorless liquid. 1H NMR (400 MHz, DMSO-d6) _ 9.05 (d, J = 1.4 Hz, 1H), 8.98 (dd, J = 1.4, 0.7 Hz, 1H), 4.39- 4.34 (m, 2H), 1.24 (t, J = 7.1 Hz, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-5-chloropyrazine, its application will become more common.

Reference:
Patent; AMGEN INC.; ALLEN, Jennifer R.; BOURBEAU, Matthew P.; BROWN, James A.; CHEN, Ning; FROHN, Michael J.; FU, Zice; LIU, Longbin; LIU, Qingyian; PETTUS, Liping H.; QIAN, Wenyuan; REEVES, Corey; SIEGMUND, Aaron C.; (362 pag.)WO2018/112094; (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. 98-97-5, name is Pyrazine-2-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C5H4N2O2

2-Pyrazinecarboxylic acid (1.5g) in thionyl chloride (10ml_) was stirred at 110C undernitrogen for 2h. The solvent was evaporated under vacuum to give 2-pyrazinecarbonyl chloride as a dark purple solid(1.5g). (4-Bromo-2-fluorophenyl)(iodo)zinc in tetrahydrofuran (0.5M, 7.02mL) was added slowly to a stirred mixture of the acid chloride (1g) and tetrakis(triphenylphosphine)palladium(0) (4O6mg) in tetrahydrofuran (5mL) at room20 temperature under nitrogen then stirred for 2h. Aqueous ammonium chloride (1M, 10ml_) was added and the reaction mixture was partitioned between ethyl acetate and water. The organic phase was dried using a hydrophobic filter tube and concentrated under vacuum. The residue was purified by chromatography on a silica column eluting with a cyclohexane:ethyl acetate gradient to give the title compound as a yellow solid (215mg).25 LC-MS: Rt 2.83min.

According to the analysis of related databases, 98-97-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2005/73189; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 6705-33-5, name is Pyrazin-2-ylmethanol, 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 6705-33-5, name: Pyrazin-2-ylmethanol

To a solution of 2-pyrazinylmethanol (500 mg, 4.54 mmol) in DCM (15 mL) at 0 C was added thionyl chloride (0.66 mL, 9.1 mmol). The reaction mixture was stirred at 0 C for 3 h. The reaction mixture was concentrated in vacuo. The crude reaction mixture was triturated with Et2O to yield the title compound as a black solid (749 mg, 4.54 mmol, 99.9%), which was used without further purification.1H NMR (400 MHz, DMSO-d6) delta 4.87 (s, 2 H), 8.63-8.69 (m, 2 H), 8.82 (d, J = 1.39 Hz, 1 H).

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; JANSSEN PHARMACEUTICA NV; CHROVIAN, Christa C.; LETAVIC, Michael A.; RECH, Jason C.; RUDOLPH, Dale A.; JOHNSON, Akinola Soyode; STENNE, Brice M.; WALL, Jessica L.; (533 pag.)WO2018/67786; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 4858-85-9, 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. 4858-85-9 name is 2,3-Dichloropyrazine, 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.

The titled compound was prepared by the reaction of 2,3-dichloropyrazine (3.0 g, 20.13 mmol) with 4-fluorophenylboronic acid (2.68 g, 19.13 mmol) using 2M sodium carbonate solution (30 mL, 60.40 mmol) and [l, -bis(diphenylphosphino)ferrocene]dichloropalladium (II) (1.16 g, 1.00 mmol) in 1,4-dioxane (60 mL) at 90 C as per the procedure described in Step 1 of Intermediate 1 to yield 1.74 g of the product; 1H NMR (300 MHz, DMSO-i) delta 7.37 (t, = 9.3 Hz, 2H), 7.83 (t, = 8.1 Hz, 2H), 8.54 (s, 1H), 8.76 (s, 1H); APCI-MS (m/z) 209 (M+H)+.

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

Reference:
Patent; GLENMARK PHARMACEUTICALS S.A.; DAS, Sanjib; GHARAT, Laxmikant Atmaram; HARDE, Rajendra Laxman; SHELKE, Sandeep Yadunath; PARDESHI, Shailesh Ramesh; THOMAS, Abraham; KHAIRATKAR-JOSHI, Neelima; SHAH, Daisy Manish; BAJPAI, Malini; (181 pag.)WO2017/21879; (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. 1196152-38-1, name is 2-Bromo-5-(trifluoromethyl)pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 2-Bromo-5-(trifluoromethyl)pyrazine

Example 44k (300 mg, 0.8 mmol), 2-Chloro-5-(trifluoromethyl)pyrimidine (199 mg, 1.09 mmol) and N,N-diisopropylethylamine (287 mul, 1.67 mmol) are dissolved in 4 ml of anhydrous DMSO and heated in a microwave reactor during 30 minutes at 150C. The crude is partitioned between EtOAc and water, the organic layer is dried over anhydrous Na2S04 then concentrated under reduced pressure to obtain 360 mg of the title product. HPLC-MS (Method 10): Rt = 3. MS (ES+): m/z = 505 [M+H]+ . The enantiomers are obtained by HPLC using a chiral stationary phase. Method for separation: HPLC apparatus type: Waters 600 Pump; column: Daicel Chiralpack AD-H, 5.0 muiotaeta, 250 mm x 20 mm; method: eluent hexane/ IPA 70:30; flow rate: 15 mL/min, Temperature: 25 C; UV Detection: 254 nm Example of separation by chiral HPLC: Submitted to separation: 665 mg of Example 1 prepared as described above; Obtained: 157 mg of enantiomer 1 (Exp. 2) and 40 mg of enantiomer 2 (Exp. 3). Example 110 is synthesized as described for example 1 starting from example 44b (60 mg of the corresponding hydrochloride, 0.15 mmol) instead of example 44k, 2-Bromo-5- (trifluoromethyl)pyrazine (42 mg, 0.19 mmol) instead 2-Chloro-5- (trifluoromethyl)pyrimidine, N,N-diisopropylethylamine (107 mu, 0.62 mmol) and 1 ml of anhydrous DMSO; the reaction mixture is heated during 30 minutes at 120C in a microwave reactor. The crude is purified by preparative HPLC-MS to obtain the title compound (24 mg, 32% yield) HPLC-MS (Method 10): Rt = 3.48 min. MS (ES+): m/z = 487 [M+H]+

According to the analysis of related databases, 1196152-38-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; HOENKE, Christoph; GIOVANNINI, Riccardo; LESSEL, Uta; ROSENBROCK, Holger; SCHMID, Bernhard; WO2015/55698; (2015); 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. 87597-21-5, name is Ethyl 6,8-dibromoimidazo[1,2-a]pyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., SDS of cas: 87597-21-5

Step B: Preparation of (6,8-dibromoimidazo[1 ,2-a]pyrazin-2-yl)methanol To a stirred solution of ethyl 6,8-dibromoimidazo[1 ,2-a]pyrazine-2-carboxylate(13.95 g, 40mmol) in toluene (558 mL) at 0 C was added 80 ml_ DIBAH (120 mmol, 3 eq, 1 .5M in toluene) dropwise. After stirring overnight at rt, the solution was poured on 1M HQ, extracted with ethyl acetate and the organic phase was washed with water, sole, dried over sodium sulphate and filtered. Removal of the solvent and recrystallyzation from DCM yielded 5.55 g (45.2 %) (6,8-dibromoimidazo[1 ,2- a]pyrazin-2-yl)methanol: 1H-NMR (300 MHz, d6-DMSO): delta =8.93 (s, 1 H), 8.05 (s, 1 H), 5.46 (bs, 1 H), 4.63 (s, 2H) ppm. UPLC-MS: RT = 0.73 min; m/z 308.0 [MH+]; required MW = 307.0.

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; BAYER PHARMA AKTIENGESELLSCHAFT; KOPPITZ, Marcus; KLAR, Ulrich; JAUTELAT, Rolf; KOSEMUND, Dirk; BOHLMANN, Rolf; BADER, Benjamin; LIENAU, Philip; SIEMEISTER, Gerhard; WO2012/80234; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 21279-62-9, These common heterocyclic compound, 21279-62-9, name is 3-Chloropyrazine-2-carboxamide, 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.

General procedure: The starting compound (1.27 mmol) was treated with 18 aliphatic amines, alicyclic amines or saturated heterocycles containing at least one nitrogen atom (2.54 mmol). Four reactions were completed by conventional heating methods. The conditions were 110 C, toluene as a solvent and pyridine (1.27 mmol) as a base. The reaction time was set to one hour. Then the reactions were completed using the microwave reactor with focused field and conditions used for syntheses were 140 C, 30 min,120 W, methanol used as a solvent and pyridine (1.27 mmol) as a base. They were set experimentally with respect to prior experience. The progress of reaction was monitored with TLC in system hexane/ethyl acetate (1:1). Then the mixture was separated by flash column chromatograph using gradient elution. Mobile phases were hexane and ethyl acetate again.

The synthetic route of 21279-62-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Jandourek, Ondrej; Dolezal, Martin; Kunes, Jiri; Kubicek, Vladimir; Paterova, Pavla; Pesko, Matus; Buchta, Vladimir; Kralova, Katarina; Zitko, Jan; Molecules; vol. 19; 7; (2014); p. 9318 – 9338;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 143591-61-1, 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. 143591-61-1, name is 3-Bromo-8-chloroimidazo[1,2-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows.

In a 2000ml three-necked flask, with mechanical stirring, Ar gas protection. Join4.62 g of 3-bromo-8-chloroimidazo [1,2-a] pyrazine (molecular weight 231, 0.02 mol)5.6 g (molecular weight 254.2, 0.022 mol) of bis (pinacolato) diboron, 23.2 g (0.0044 mol) of Pd (dppf) Cl, 36 g (molecular weight 138,1,4-dioxane 500ml. Start mechanical stirring,After 3 times of evacuation under reduced pressure to maintain Ar gas protection,The reaction was monitored by TLC (thin layer chromatography)Until the complete disappearance of raw materials, reflux for 3 hours, the reaction was complete. Let cool, the reaction system divided into two layers, the organic layer was separated and evaporated to dryness to give 5.04g product, yield 90.2%.

The chemical industry reduces the impact on the environment during synthesis 3-Bromo-8-chloroimidazo[1,2-a]pyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Beijing Dingcai Technology Co., Ltd.; Li Yinkui; Tang Jinming; Fan Hongtao; (34 pag.)CN104650116; (2017); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem