Author: Jessica.F

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. 75907-74-3, name is (3,5,6-Trimethylpyrazin-2-yl)methanol, A new synthetic method of this compound is introduced below., name: (3,5,6-Trimethylpyrazin-2-yl)methanol

Step (1): in 50mL flask it contained QR01006-IN-01 (500mg, 3.29mmol), dichloromethane (10mL), and chloromethyl chloroformate (460mg, 3.6mmol), at -2 degrees and pyridine (0.32mL) was added dropwise to control the temperature not exceeding 3C. The reaction was warmed to room temperature overnight. TLC (petroleum ether/ethyl acetate=1/3) was done to monitor the completion of the reaction. The reaction was filtered and the filtrated was dried to give 1.1g yellow oil which was purified by preparative plate to give 620mg of yellow solid, yield: 77.3%. LCMS and HNMR spectra were used to confirm the structure.

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; Wuhan Langlai Science and Technology Development Co., Ltd.; Wuhan Qirui Pharmaceuticals Co., Ltd.; Ge, Jian; Ma, Jianyi; Xiang, Guangya; Wang, Wei; Wang, Chaodong; (44 pag.)CN105237527; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 914452-71-4, name is 2-Bromo-6-methylpyrazine, 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 914452-71-4, category: Pyrazines

General procedure: To a solution of Example 4A (50 mg, 0.176 mmol) in dioxane (0.8 mL) were added tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3, 8.0 mg, 8.78 mumol), xantphos (10.2 mg, 0.018 mmol) and 2-chloro-3-methylpyrazine (24.8 mg, 0.193 mmol). Then potassium carbonate (72.8 mg, 0.527 mmol) was added. The reaction mixture was stirred overnight at 80 C. The reaction mixture was filtered, and the solids were washed with acetonitrile (3 ¡Á 2 mL). The filtrate and washes were concentrated under reduced pressure, and the residue was purified by preparative HPLC (Phenomenex Luna C8(2) 5 mum 100A AXIA column (30 mm ¡Á 75 mm); a gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/minute (0-1.0 minute 5% A, 1.0-8.5 minutes linear gradient 5-100% A, 8.5- 11.5 minutes 100% A, 11.5-12.0 minutes linear gradient 95-5% A) to give the title compound (50 mg, 0.13 mmol, 76% yield). The reaction and purification conditions described in Example 579 substituting 2- bromo-6-methylpyrazine (33.4 mg, 0.193 mmol) for 2-chloro-3-methylpyrazine (24.8 mg, 0.193 mmol) gave the title compound. 1H NMR (501 MHz, DMSO-d6) delta ppm 8.73 (s, 1H), 7.72 (s, 1H), 7.63 (s, 1H), 7.60 (s, 1H), 7.50 (t, J = 8.9 Hz, 1H), 7.08 (dd, J = 11.4, 2.8 Hz, 1H), 6.86 (ddd, J = 8.9, 2.9, 1.2 Hz, 1H), 4.50 (s, 2H), 2.33 (s, 6H), 2.27 (s, 3H); MS (ESI+) m/z 377 (M+H)+.

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; CALICO LIFE SCIENCES; ABBVIE, INC.; SIDRAUSKI, Carmela; PLIUSCHEV, Marina; FROST, Jennifer, M.; BLACK, Lawrence, A.; XU, Xiangdong; SWEIS, Ramzi, Farah; SHI, Lei; ZHANG, Qinwei, I.; TONG, Yunsong; HUTCHINS, Charles, W.; CHUNG, Seungwon; DART, Michael, J.; (661 pag.)WO2017/193063; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 63744-22-9,Some common heterocyclic compound, 63744-22-9, name is 6,8-Dibromoimidazo[1,2-a]pyrazine, molecular formula is C6H3Br2N3, 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.

Into a 250-mL 3 -necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, were placed 6,8-dibromoimidazo[l,2-a]pyrazine (5 g, 18.06 mmol, 1.00 equiv) and /V, /V-di methyl formam i dc (125 mL). This was followed by the addition of (0249) NIS (4.3 g, 19.11 mmol, 1.05 equiv), in portions at room temperature. The resulting solution was stirred overnight at 60 C in an oil bath. The reaction mixture was cooled to room temperature with a water/ice bath and then quenched with water. The resulting solution was extracted with ethyl acetate and the organic layers combined and concentrated under vacuum. Purification by flash chromatography (silica gel column with ethyl (0250) acetate/petroleum ether (1/2)) provided 2.8 g (38%) of 5-1 as a white solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6,8-Dibromoimidazo[1,2-a]pyrazine, its application will become more common.

Reference:
Patent; IDEAYA BIOSCIENCES, INC.; BECK, Hilary, Plake; GONZALEZ-LOPEZ, Marcos; SUTTON, James, Clifford, Jr.; (86 pag.)WO2019/156989; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 14508-49-7, The chemical industry reduces the impact on the environment during synthesis 14508-49-7, name is 2-Chloropyrazine, I believe this compound will play a more active role in future production and life.

The reaction was run under nitrogen atmosphere. 2-chloropyrazine (96 mL, 1073 mmol) was added dropwise to 35 wt aqueous hydrazine (544 mL, 6009 mmol) at 65 C over 1 h. After the addition, stirring was continued at 63-67 C for 16 h then let stand at room temperature for two days. The mixture was filtered to remove a small amount of precipitate, then extracted with 10% iPrOH/dichloromethane (5 x 250 mL). The combined organic extracts were dried (MgS04), filtered, then concentrated under reduced pressure. The resulting solid was triturated with isopropyl acetate (600 mL). The solid was collected by filtration, rinsed with isopropyl acetate and dried under vacuum to give 2-hydrazinylpyrazine (60 g, 51 %) as a pale yellow solid. LCMS m/z = 111.2 [M+H]+. lU NMR (400 MHz, DMSO-i ) delta 4.21 (s, 2H), 7.70 (d, = 2.8 Hz, 1H), 7.89 (s, 1H), 7.93 (dd, = 2.8, 1.5 Hz, 1H), 8.10 (d, = 1.5 Hz, 1H).

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-Chloropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ARENA PHARMACEUTICALS, INC.; BLACKBURN, Anthony C.; HAN, Sangdon; JONES, Robert M.; MONTALBAN, Anthony Garrido; PAL, Biman B.; RUETER, Jaimie Karyn; WO2012/116276; (2012); 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. 873-42-7, name is 2-Amino-3,5-dichloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. name: 2-Amino-3,5-dichloropyrazine

STEP4 Preparation of 6,8-dichloro-3-((3aR,4S,6aS)-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-yl)imidazo[1,2-a]pyrazine COCl2 (2.13 ml, 4.27 mmol) was added dropwise over 15 min to a solution of dimethylsulfoxide (0.39 g, 4.98 mmol) in DCM (30 mL) cooled with a dry ice-acetone bath. To this solution was added a solution of (S)-2-chloro-2-((3aR,4R,6aS)-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-yl)ethanol (0.85 g, 3.56 mmol) over 5 min. The mixture was further stirred at -78 C. for 45 min. TEA (0.26 ml, 1.89 mmol) was added to the solution, stirred at -40 C. for 30 min and allowed to warm up to room temperature. The organic phase was washed with sat. NH4Cl solution and brine, dried over Na2SO4 and filtered. After removal of the solvent, the resulting residue (760 mg) was dissolved in CH3CN. To this solution was added 3,5-dichloropyrazin-2-amine (584 mg, 3.56 mmol), stirred at 85 C. for 16 h and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hexanes:EtOAc:DCM=2:1:1) to give 6,8-dichloro-3-((3aR,4S,6aS)-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-yl)imidazo[1,2-a]pyrazine (36 mg, 3%) as a white sticky oil. 1H-NMR (CDCl3, 400 MHz): delta 8.08 (s, 1H), 7.65 (s, 1H), 5.13-5.05 (m, 2H), 4.54 (d, 1H, J=2.4 Hz), 3.13-3.01 (m, 2H), 1.61 (s, 3H), 1.39 (s, 3H).

The synthetic route of 873-42-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; HANDOK INC.; Lee, Jin-Hwa; Kim, Seung-Yong; Kim, Do-Ran; Ahn, Koo-Hyeon; Lee, Gwi-Bin; Kim, Doo-Seop; Hwang, Hyun-Sook; (74 pag.)US2017/204101; (2017); 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. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., Computed Properties of C6H5ClN2O2

Diisobutylaluminum hydride (4.29 mL, 4.29 mmol) was added dropwise over 5 min to a solution of methyl 5-chloropyrazine-2-carboxylate (185 mg, 1.07 mmol) in tetrahydrofuran (10 mL) at -70 0C under an athmosphere of nitrogen. The reaction mixture was stirred at – 70 0C for 5 min and then allowed to reach ambient temperature and stirred over night. The reaction mixture was cooled on ice and approximately 2 mL of 1 M sodium hydroxide was added dropwise while stirring. The reaction mixuture was diluted with diethyl ether and stirred for 45 min at ambient temperature and then filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography using a gradient of ethyl acetate in heptane to yield 43 mg (28 %) of the title product; 1H NMR (400 MHz, DMSO- dbeta) delta ppm 8.72 (d, 1 H), 8.52 – 8.55 (m, 1 H), 5.71 (t, 1 H), 4.64 (d, 2 H);

The synthetic route of 33332-25-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; WO2008/130320; (2008); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 1245644-42-1,Some common heterocyclic compound, 1245644-42-1, name is 6-Bromo-3-iodoimidazo[1,2-a]pyrazine, molecular formula is C6H3BrIN3, 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: [0199] A suspension of tributyl(R2)stanne (3.11 mmol), 6-bromo-3-iodo-imidazo[1,2-a]pyrazine 17* (3.11 mmol) andPd(PPh3)4 (0.93 mmol) in dioxane (20 mL) was heated to 150 C in a microwave tube for 20 minutes. The resultingmixture was filtered through celite and evaporated under reduced pressure. If necessary, the reaction was then carriedout more times on the same scale. The crude products were combined and purified by flash chromatography to give theintermediate 18*.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6-Bromo-3-iodoimidazo[1,2-a]pyrazine, its application will become more common.

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

Electric Literature of 1458-18-0, 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. 1458-18-0 name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, 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.

Step 1: Methyl 3-amino-6-chloro-5-(2-fluorophenyl)pyrazine-2-carboxylate A mixture of methyl 3-amino-5,6-dichloropyrazine-2-carboxylate (10.0 g, 45 mmol, Ark Pharm, Inc., Arlington Heights, Ill.), (2-fluorophenyl)boronic acid (6.93 g, 49.5 mmol, Combi-Blocks, San Diego, Calif., USA) and potassium carbonate (13.1 g, 95 mmol) in a 10:1 mixture of DME/water (220 mL) was degassed with nitrogen for 5 min and then tetrakis(triphenylphosphine)palladium(0) (1.04 g, 0.90 mmol) was added. The reaction mixture was stirred at 90 C. for 16 h, then was allowed to cool to room temperature and partitioned between EtOAc (200 mL) and 1 N HCl (200 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated to provide methyl 3-amino-6-chloro-5-(2-fluorophenyl)pyrazine-2-carboxylate. m/z (ESI, +ve): 282.1 (M+H)+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; Amgen Inc.; LANMAN, Brian Alan; CHEN, Jian; REED, Anthony B.; CEE, Victor J.; LIU, Longbin; KOPECKY, David John; LOPEZ, Patricia; WURZ, Ryan Paul; NGUYEN, Thomas T.; BOOKER, Shon; NISHIMURA, Nobuko; SHIN, Youngsook; TAMAYO, Nuria A.; ALLEN, John Gordon; ALLEN, Jennifer Rebecca; (266 pag.)US2018/334454; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 1458-01-1, The chemical industry reduces the impact on the environment during synthesis 1458-01-1, name is Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate, I believe this compound will play a more active role in future production and life.

Preparation 1 3-Chloro-pyrazine-2,6-diamine Lithium hydroxide (12.4 g, 0.30 mol) was added to a stirred suspension of 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester (20 g, 99 mmol) in methanol (300 ml) and water (120 ml) and the reaction heated at 90¡ã C. for 1.5 hours before allowing to cool to room temperature. The reaction was concentrated in vacuo to afford a yellow slurry and this was suspended in 1,4-dioxane (350 ml) and 2M aqueous HCl solution (200 ml,) was added. The mixture was heated at 100¡ã C. for 2 hours and then allowed to cool before removing the 1,4-dioxane in vacuo. The resulting aqueous solution was taken to pH 8 using sodium carbonate (saturated aqueous) and extracted into ethyl acetate (3*300 ml). The combined organic layers were washed with brine (300 ml), dried (Na2SO4) and concentrated in vacuo to afford a yellow solid (11.7 g, 82percent). 1H-NMR (d6-DMSO): 5.95 (br s, 2H), 6.02 (br s, 2H), 6.82 (s, 1H). MS m/z 147 [MH]+

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, Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Pfizer Limited; US2007/105872; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 5521-58-4, name is 5-Methylpyrazin-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 5521-58-4, Quality Control of 5-Methylpyrazin-2-amine

3-{[5-(Azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]-benzoic acid (1.0 eq), (1.00 mol eq), 5-methylpyrazin-2-amine (1.12 mol eq) and 2-methyltetrahydrofuran (2.00 rel vols) were charged to a vessel and stirred at 20 C. N-methylmorpholine (5.00 mol eq) was added followed by a line-wash with 2-methyl-tetrahydrofuran (0.50 rel vols). A 50 wt % solution of 1-propanephosphonic acid cyclic anhydride (T3P) in 2-methyltetrahydrofuran (1.70 mol eq) was charged followed by a line wash with 2-methyltetrahydrofuran (0.50 rel vols). The resulting mixture was heated to 78 C. over 30 minutes and the clear yellow solution was held at 78 C. for roughly 22 hours, then checked for acceptable conversion. At the end of reaction the solution was further diluted with 2-methyltetrahydrofuran (7.00 rel vols) and the temperature was adjusted to 45 C. 5 wt % aq. sodium bicarbonate solution (6.00 rel vols) was slowly added over 30 mins to the stirring solution causing gas evolution. After 15 minutes stirring was turned off and the phases were allowed to separate over 30 minutes. The lower aqueous phase was drained off 20 wt % aq. phosphoric acid (3.30 rel vols) was charged to the stirring organic phase. After 15 minutes stirring the phases were allowed to separate and the lower aqueous phase was drained off again. A mixture of 20 wt % aq. phosphoric acid (1.50 rel vols) and water (1.50 rel vols) was charged to the stirring organic phase. After 15 minutes, stirring was turned off and the mixture held overnight for phase separation. The lower (aqueous) phase was drained off again. 5 Wt % aq. sodium bicarbonate (4.50 rel vols) was added over at least 10 mins to the stirring solution. After phase separation the lower (aqueous) phase was run off again. The resulting solution was dried by azeotropic distillation to a concentration of approximately 241 mg/g, collecting around 0.48 rel vols of the lower distillate phase. Heptane (1.60 rel vols) was added over 10 mins to the dry solution at above 50 C. before the batch was cooled to 40 C. The solution was seeded with 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]-N-(5-methylpyrazin-2-yl)benzamide (Form 1 Seed, 0.0010 rel wt) before an overnight temperature program was applied: held at 40 C. for 2 hrs; cooled to 35 C. at 0.1 C./min (50 minutes); held for 2 hours; cooled to 30 C. at 0.1 C./min (50 minutes); held for 2 hours; cooled to 0 C. at 0.1 C./min (300 minutes); and held for at least 2 hours. After crystallisation overnight, further heptane (4.1 rel vols) was added over 2.0 hours to reduce losses to liquors to <4.0 mg/mL. The suspension was then filtered followed by a line rinse with a pre-mixed solution of heptane (2.10 rel vols) and 2-methyltetrahydrofuran (0.90 rel vols) and transferred to a filtration apparatus. The filter cake was dried to constant weight at 40 C. to furnish crude 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]-N-(5-methylpyrazin-2-yl)benzamide in 86-89% as Form I. 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-Methylpyrazin-2-amine, other downstream synthetic routes, hurry up and to see. Reference:
Patent; AstraZeneca AB; US2010/210841; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem