Tag: M.W=200-300

Adding a certain compound to certain chemical reactions, such as: 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, 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 76537-18-3, category: Pyrazines

Step 1: 5-Chloro-3-((trimethylsilyl)ethynyl)pyrazin-2-amineTo a 500 mL round-bottomed flask was added 3-bromo-5-chloropyrazin-2-amine (5 g, 23.99mmol), ethynyltrimethylsilane (10.17 ml, 72.0 mmol), and triethylamine (33.4 ml, 240 mmol)in THF (100 ml) to give a brown solution. The reaction was degassed and purged withnitrogen. To the stirring solution was added bis(triphenylphosphine)palladium(ll) chloride (1.684g, 2.399mmo1) and copper(l) iodide (914mg, 4.8Ommol). The reaction was stirred at room temperature for 30mins. The reaction was extracted into ethyl acetate, washed with brine, the organic layer separated, dried over Mg504, filtered and the solvent removed underreduced pressure. The crude product loaded onto silica was purifiied by flash column chromatography elution with iso hexane:ethyl acetate (0-30%) using an 80g silca cartridge. The required fractions were combined and the solvent removed under reduced pressure to yield a brown solid;LCMS: Rt = 1 .29mins MS mlz 226.2 [M+H]+; Method 2minLowpHvo2.1H NMR (400MHz, DMSO-d6) O 8.08 (1H, 5), 6.82 (2H, broad 5), 0.27 (9H, 5).

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-Bromo-5-chloropyrazin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NOVARTIS AG; BELLENIE, Benjamin Richard; BLOOMFIELD, Graham Charles; BRUCE, Ian; CULSHAW, Andrew James; HALL, Edward Charles; HOLLINGWORTH, Gregory; NEEF, James; SPENDIFF, Matthew; WATSON, Simon James; (395 pag.)WO2015/162459; (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. 330786-09-9, name is Methyl 3,5-dichloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., name: Methyl 3,5-dichloropyrazine-2-carboxylate

The mixture of methyl 3,5-dichloropyrazine-2-carboxylate (1.0 g, 4.83 mmol, CAS 330786-09-9), (3ri)-l,3-dihydrospiro[indene-2,4′-piperidin]-3-amine dihydrochloride (1.65 g, 4.83 mmol, Intermediate I) and CsF (3.66 g, 24.1 mmol) in DMF (15 mL) was stirred at 70 C for 2 hours. Boc20 (1.57 g, 7.24 mmol) and TEA (1 mL) were then added to the mixture and the mixture was stirred at 20 C for 1 hour. The mixture was diluted with H20 (50 mL), and extracted with EtOAc (50 mL x 2). The organic layer was washed with brine (50 mL), dried over anhydrous Na2S04, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether / ethyl acetate = l : 0 ~ 5 : l) to afford methyl 5-[(3ri)-3-{[(/er/-butoxy)carbonyl]amino}-l,3-dihydrospiro[indene-2,4′- piperidin]-l’-yl]-3-chloropyrazine-2-carboxylate (1.58 g, 69% yield) as a yellow solid. LCMS m/z [M+H]+ = 473.1.

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; RELAY THERAPEUTICS, INC.; D.E. SHAW RESEARCH, LLC; TAYLOR, Alexander, M.; LESCARBEAU, Andre; KELLEY, Elizabeth, H.; SHORTSLEEVES, Kelley, C.; WALTERS, W., Patrick; MURCKO, Mark, Andrew; MCLEAN, Thomas, H.; GUNAYDIN, Hakan; GIORDANETTO, Fabrizio; THERRIEN, Eric; (607 pag.)WO2019/183367; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 87486-34-8, These common heterocyclic compound, 87486-34-8, name is 3,5-Dibromo-1-methylpyrazin-2(1H)-one, 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 12 L threenecked RBF equipped with an overhead stirrer and reflux condenser was chargedsequentially with (-)-1,4-dimethyl-3-(4-aminophenyl)piperazin-2-one (V, 491 g, 2.24 mol), 3,5-dibromo-1-methylpyrazin-2(1H)-one (VI, 600 g, 2.24 mol), i-PrOH (5 L) and triethylamine (350mL, 2.5 mol). The resulting suspension was heated at 82 °C for 24 h (Caution: reaction was exothermic).After the reaction mixture was cooled for 5 h, 1.25 L of 2 M Na2CO3solution was added and the suspension was stirred overnight. The orange solids were then collected on afritted funnel and washed with 2 L of fresh IPA (color was washed off). The resulting tan solids were suspended in 3L of deionized water and stirred at 25 °C for 1 h. After filtration, the solids were washed with1 L of methyl tert-butyl ether (MTBE)and dried under vacuum in the funnel at 25 °C for 1 h and in an amber glass at40 °C overnight. White solids wereobtained as compound VII (629 g, 69percent).

Statistics shows that 3,5-Dibromo-1-methylpyrazin-2(1H)-one is playing an increasingly important role. we look forward to future research findings about 87486-34-8.

Reference:
Article; Young, Wendy B.; Barbosa, James; Blomgren, Peter; Bremer, Meire C.; Crawford, James J.; Dambach, Donna; Gallion, Steve; Hymowitz, Sarah G.; Kropf, Jeffrey E.; Lee, Seung H.; Liu, Lichuan; Lubach, Joseph W.; Macaluso, Jen; Maciejewski, Pat; Maurer, Brigitte; Mitchell, Scott A.; Ortwine, Daniel F.; Di Paolo, Julie; Reif, Karin; Scheerens, Heleen; Schmitt, Aaron; Sowell, C. Gregory; Wang, Xiaojing; Wong, Harvey; Xiong, Jin-Ming; Xu, Jianjun; Zhao, Zhongdong; Currie, Kevin S.; Bioorganic and Medicinal Chemistry Letters; vol. 25; 6; (2015); p. 1333 – 1337;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 957344-74-0, The chemical industry reduces the impact on the environment during synthesis 957344-74-0, name is 5,8-Dibromoimidazo[1,2-a]pyrazine, I believe this compound will play a more active role in future production and life.

Step 1 (5-Bromo-iotamiotadazo[ 1 , 2-a]pyraziotan-8-yl)-(4-methanesulfonyl-phenyl) -amine[00270] A degassed mixture of 5,8-dibromo-imidazo[l,2-a]pyrazme (2.19g, 7.916mmol), A- methylsulfonylamlme (1 49g, 8.708mmol), Pd2dba3 (145mg, 0.15mmol) and Xantphos (183mg, 0.317mmol), m dry toluene (5OmL) is stirred at 1100C for 16 hours. After evaporation of the solvent, the residue is purified by silica gel column chromatography elutmg with 95:5 DCM:NH3 (7M in MeOH). The title compound (1.496g, 51%) is isolated containing some starting material (20%) and used in the next step without further purification.

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, 5,8-Dibromoimidazo[1,2-a]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GALAPAGOS N.V.; WO2007/131991; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 143591-61-1, name is 3-Bromo-8-chloroimidazo[1,2-a]pyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Quality Control of 3-Bromo-8-chloroimidazo[1,2-a]pyrazine

Example 7-1 : Preparation of N-cyclopropyl-4-[8-(pentylamino)imidazo[1 ,2- a]pyrazin-3-yl]benzamide3-bromo-8-chloro-imidazo[1 ,2-a]pyrazine (intermediate example 1 -1 , 0.15 mmol, 0.75 mL, 0.2M in NMP), 1 -pentanamine (1.5 eq, 0.3 mL, 0.5 M in NMP) and DIPEA (3 eq, 77 mu) were combined in a sealed vial and heated at 160 C under microwave irradiation for 60 min. After cooling, [4-[(cyclopropylamino)carbonyl]phenyl]- boronic acid (1.5 eq, 0.45 mL, 0.5 M in NMP), Pd(dppf)Cl2 (0.1 eq, 400 mu, 0.0375 M in NMP) and potassium carbonate (450 muIota_, 1M in water) were added and the mixture was heated at 160 C under microwave irradiation for 80 min. After cooling, the solution was filtered and subjected to preparative HPLC to give N- cyclopropyl-4-[8-(pentylamino)imidazo[1 ,2-a]pyrazin-3-yl]benzamide (3.8 mg, 7 %): UPLC-MS: RT = = 0.83 min; m/z (ES+) 364.5 [MH+]; required MW = 363.5

The synthetic route of 143591-61-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; KOPPITZ, Marcus; KLAR, Ulrich; JAUTELAT, Rolf; KOSEMUND, Dirk; BOHLMANN, Rolf; BADER, Benjamin; LIENAU, Philip; SIEMEISTER, Gerhard; WO2012/80229; (2012); 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 51171-02-9 as follows. Formula: C6H5BrN2O2

Step 2: synthesis of N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-oxo-6,7-dihydrothieno[2,3-b]pyrazine-6-carboxamide (100)[0306]A solution of 3-(2-cyanopropan-2-yl)-N-(3-(2-mercaptoacetamido)-4-methylphenyl)benzamide 16 (0.054 mmol, 20 mg), methyl 3-bromopyrazine-2-carboxylate 101 (0.054 mmol, 11.8 mg) and Na2CO3 (1.2 eq, 7 mg) in ethanol (1 mL) was stirred overnight at 70 C. The reaction mixture was quenched in cold 1N HCl solution and extracted with CH2Cl2. Organic layer was dried and evaporated. Purification by chromatography (0-10% methanol in CH2Cl2) gave N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-oxo-6,7-dihydrothieno[2,3-b]pyrazine-6-carboxamide 102 (11 mg, 42.9%). NMR (400 MHz, DMSO-d6) 1.77 (s, 6H), 2.35 (s, 3H), 7.15 (d, J=8.6 Hz, 1H), 7.48 (dd, J=8.2 Hz and 2.3 Hz, 1H), 7.59 (t, J=7.8 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.97 (d, J=7.8 Hz, 1H), 8.07 (t, J=2.0 Hz, 1H), 8.54 (br s, 1H), 8.62 (br s, 1H), 8.66 (d, J=1.6 Hz, 1H), 10.29 (s, 1H). (m/z)=473 (M+H)+.

According to the analysis of related databases, 51171-02-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Folmer, Brigitte Johanna Bernita; Man, de Adrianus Petrus Antonius; Gernette, Elisabeth Sophia; Corte Real Goncalves Azevedo, Rita; Ibrahim, Hemen; US2013/79341; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 5900-13-0, 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. 5900-13-0 name is 5-Bromo-3-methoxypyrazin-2-amine, 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.

5-Bromo-3-methoxy-pyrazin-2-ylamine (A) (816 mg, 4 mmol) and phenyl boronic acid (732 mg , 6 mmol) in toluene (5 mL), ethanol (5 mL) and Na2CO3 (8 mmol, 1 M aqueous) was purged with nitrogen for 10 minutes, and was added PdCl2(PPh3)2 (140 mg, 0.2 mmol). The reaction mixture was stirred at 85 0C for 4 hours. The reaction mixture was cooled to room temperature and diluted with EtOAc (50 mL). The solution was washed with brine (2 X 5 mL). The organic extracts was dried with MgSO4, then solvent was removed under vacuum. The residue was purified with flash column to give product B (660 mg, 82%) as yellow solid. 1H NMR (400 MHz, CDCl3): delta 8.08 (IH, s), 7.92 (2H, d), 7.46 (3H, m), 4.94 (2H, bs), 4.12 (3H, s); MS: 202 (M + H+).

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

Reference:
Patent; NOVARTIS AG; WO2008/73305; (2008); 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 5900-13-0 as follows. Product Details of 5900-13-0

EXAMPLE 49 Sodium hydride (oil free; 0.053 g) was added to a solution of 2-amino-5-bromo-3-methoxypyrazine (0.151 g) in DME (5 ml). The solution was stirred for 10 minutes and then a solution of 4′-methyl-2-biphenylsulphonyl chloride (0.198 g) in DME (2 ml) was added. The solution was allowed to stand for 1 hour and then water (25 ml) was added. 2M Hydrochloric acid (2 ml) was added and the mixture was extracted eith ethyl acetate (2*25 ml). The extracts were washed with water (25 ml) and saturated sodium chloride solution (25ml) and dried (MgSO4). Volatile material was removed by evaporation and the residue was recrystallized from ethyl acetate to give N-(5-bromo-3-methoxy-2-pyrazinyl)-4′-methyl-2-biphenylsulphonamide (0.12 g) m.p. 204-206 C.; 1 H NMR (d6 -DMSO): 2.4 (s,3H), 3.85(s,3H), 7.05-7.2(m,4H), 7.3(dd,1H), 7.55-7.7(m,2H), 7.8(s,1H), 8.1(dd,1H); mass spectrum (+ve FAB, methanol/NBA): 436 (M+H)+.

According to the analysis of related databases, 5900-13-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Zeneca Limited; US5861401; (1999); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 330786-09-9, 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. 330786-09-9, name is Methyl 3,5-dichloropyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of methyl 3,5-dichloropyrazine-2-carboxylate (100 mg, 0.483 mmol) in dioxane (1.93 mL) were added tert-butyl (4-methylpiperidin-4-yl)carbamate (109 mg, 0.507 mmol) and TEA (0.141 mL, 1.01 mmol) and the resulting mixture was stirred at 24 C for 18 h. H20 (20 mL) was added, and the layers were separated. The aqueous phase was extracted with EtOAc (3 x 20 mL), the combined organic layers were washed with sat NaCl, dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified via silica gel chromatography (0 – 100 % EtOAc in hexanes) to give the title compound (120 mg, 64%) as pale yellow solid. MS (ES+) C17H25CIN4O4 requires: 384, found: 407 [M+Na]+. ‘H NMR (500 MHz, Chloroform-c d 7.88 (s, 1H), 4.40 (s, 1H), 3.96 (s, 3H), 3.71 – 3.57 (m, 2H), 3.46 – 3.27 (m, 2H), 2.19 – 2.04 (m, 2H), 1.74 – 1.62 (m, 2H), 1.54 – 1.34 (m, 12H). Also isolated regioisomer methyl 5-(4-((tert-butoxycarbonyl)amino)-4-methylpiperidin-l-yl)-3- chloropyrazine-2-carboxylate (60 mg, 32%) as a pale yellow solid. 1 H NMR (500 MHz, Chloroform-c ) d 8.03 (s, 1H), 4.41 (s, 1H), 4.06 – 3.96 (m, 2H), 3.95 (s, 3H), 3.53 – 3.39 (m, (0708) 2H), 2.26 – 2.12 (m, 2H), 1.72 – 1.57 (m, 2H), 1.50 – 1.37 (m, 12H).

The chemical industry reduces the impact on the environment during synthesis Methyl 3,5-dichloropyrazine-2-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM; JONES, Philip; CROSS, Jason; BURKE, Jason; MCAFOOS, Timothy; KANG, Zhijun; (154 pag.)WO2019/213318; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 143591-61-1,Some common heterocyclic compound, 143591-61-1, name is 3-Bromo-8-chloroimidazo[1,2-a]pyrazine, molecular formula is C6H3BrClN3, 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 149; The mixed halo-products (3:1 Cl:Br) from Preparative Example 102 (3.67 g, 15.0 mmol), were combined with N,N-dimethyl-m-phenylenediamine.2HCl (4.71 g, 22.5 mmol), i-Pr2NEt (15.7 mL, 90.2 mmol), and NMP solvent (75 mL). The reaction was heated in an oil bath at 160 C. for 18 hours. The reaction was cooled and concentrated under vacuum. The crude material was purified by column chromatography; 2 columns using a gradient of 20% EtOAc/Hexanes increasing to 50% EtOAc/Hexanes. The product 149 was isolated in 95% purity as determined by 1H NMR (400 MHz DMSO-d6,) 9.36 (s, 1H), 7.77 (s, 1H), 7.74 (d, J=4.4 Hz, 1H), 7.54 (d, J=4.8 Hz, 1H), 7.47 (m, 1H), 7.42 (t, J=2.0 Hz), 7.09 (t, J=8.0 Hz, 1H), 6.40 (dd, J=8.0 Hz, 2.0 Hz, 1H), 2.87 (s, 6H). Product was isolated in 77% yield, 3.83 g.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Bromo-8-chloroimidazo[1,2-a]pyrazine, its application will become more common.

Reference:
Patent; Schering Corporation; US2007/117804; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem