Month: July 2021

Reference of 68774-77-6, A common heterocyclic compound, 68774-77-6, name is 8-Chloro[1,2,4]triazolo[4,3-a]pyrazine, molecular formula is C5H3ClN4, 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 the product of Example 365A (70 mg, 0.153 mmol) in N,N- dimethylformamide (1 mL) was added 8-chloro-[1,2,4]triazolo[4,3-a]pyrazine (35.5 mg, 0.230 mmol) and N,N-diisopropylethylamine (0.080 mL, 0.460 mmol). The reaction mixture was stirred for 4 days at 70 C and then was purified by preparative HPLC [Waters XBridge C18 5 mum OBD column, 30 × 100 mm, flow rate 40 mL/minute, 5-100% gradient of acetonitrile in buffer (0.1 % trifluoroacetic acid)] to give the title compound (15 mg, 0.026 mmol, 17% yield). 1H NMR (400 MHz, DMSO-d6) delta ppm 9.17 (s, 1H), 7.75 (d, J = 4.8 Hz, 1H), 7.54 (s, 1H), 7.45 (t, J = 8.9 Hz, 1H), 7.23 (d, J = 4.9 Hz, 1H), 7.00 (dd, J = 11.4, 2.9 Hz, 2H), 6.79 (ddd, J = 9.0, 2.9, 1.2 Hz, 1H), 4.42 (s, 2H), 4.17 – 4.14 (m, 2H), 2.64 – 2.50 (m, 1H), 2.35 (ddd, J = 12.8, 9.4, 2.9 Hz, 1H), 2.27 – 2.13 (m, 1H), 2.04 – 1.77 (m, 8H); 19F NMR (376 MHz, DMSO-d6) delta ppm -75.00, -114.17; MS (ESI+) m/z 461 (M+H)+ .

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; 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

Electric Literature of 186534-02-1, These common heterocyclic compound, 186534-02-1, name is 3,5,6-Trimethylpyrazine-2-carbaldehyde, 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.

In a 50 mL round-bottom flask freshly prepared TMP-CHO (150 mg 1 mmol) was added and dissolved in 20 mL of 1 2-dichloroethane propargylamine (66 mg 1.2 mmol) was added slowly at room temperature the reaction was run at at room temperature for 2 hours triacetoxy sodium borohydride (424 mg 2 mmol) was added and monitored by TLC about 2 hours later the reaction was complete 10 mL of 10 K2CO3was added for quenching. The resulting material was extracted with dichloromethane dried over anhydrous sodium sulfate filtered and concentrated and purified with silica gel column chromatography (ethyl acetatepetroleum ether 32) to give the compound MT-012 as a yellow solid (163mg 86) . ESI-MS [M+H]+m/z 190.3.1H-NMR (CDCl3) 3.96 (s 2H) 3.56 (d J2.4 Hz 2H) 2.51 (s 3H) 2.49 (s 6H) 2.26 (t J2.4 Hz 1H) .

Statistics shows that 3,5,6-Trimethylpyrazine-2-carbaldehyde is playing an increasingly important role. we look forward to future research findings about 186534-02-1.

Reference:
Patent; GUANGZHOU MAGPIE PHARMACEUTICAL CO., LTD; WANG, Yuqiang; YOUDIM, Moussa B.H.; SUN, Yewei; ZHANG, Zaizun; ZHANG, Gaoxiao; YU, Pei; YI, Peng; LIANG, Ming; LIU, Wei; WO2015/109935; (2015); 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. 69214-33-1, name is 8-Chloroimidazo[1,2-a]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C6H4ClN3

Intermediate Example 2-1 : Preparation of 3-bromo-8-chloro-imidazo[1 ,2- ajpyrazineTo a stirred solution of 8-chloro-imidazo[1 ,2-a]pyrazine (164.2 g g, 1070 mmol) in 950 mL DMF is added NBS (190.3 g, 1070 mmol) in one portion and the mixture is stirred overnight at rt. The mixture is poured on 9500 mL water, filterd and the residue is washed with water (2 x 1000 mL) and dried in vaccuo to yield 152.6 g (61.4 %) of the title compound. 1H-NMR (300 MHz, d6-DMSO): delta =8.45 (d, 1 H), 8.00 (s, 1 H), 7.83 (d, 1 H) ppm.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 69214-33-1.

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

Synthetic Route of 109838-85-9, 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. 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

2,5-Dihydro-3,6-dimethoxy-2-isopropyl-5-(2′-iodo-4\5′-dibenzyloxybenzyl)- (2R,5S)-pyrazine (32); The diastereomeric product 32 was obtained by a reaction of the lithium salt of the chiral auxiliary (2R)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine with the bromo derivative 30 using a modification of a procedure reported in the literature [U. Schollkopf, “Enantioselective Synthesis of Non-Proteinogenic Amino Acids via Metallated Bis-Lactim Ethers of 2,5-Diketopiperazines.” Tetrahedron. 39, pp 2085-2091 (1983)]. Specifically, (2R)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (15.7 mmol) was dissolved in 10 mL of THF (freshly distilled from LiAlH4). The light yellow solution was cooled to -78° C (dry ice/acetone bath) and stirred for 15 min under argon. A 2.5 M solution of n-butyl lithium (15.7 mmol) was added drop wise over a period of 10 min and the mixture was stirred for 20 min at -78° C. In a separate flask CuCN (7.86 mmol) was stirred with 10 mL of freshly distilled THF at room temperature for 10 min. The white suspension was then cooled to 0° C (ice bath) and stirred at that temperature for 20 min. The n-BuLi reaction mixture was then transferred to the white suspension of CuCN/THF under argon using a cannula. The resulting yellow suspension turned into a yellow solution within two minutes. The reaction mixture was then stirred at 0° C for 15 min and cooled to -78° C. After 15 min of stirring at -78° C, a solution of bromo derivative 30 (7.86 mmol) in 20 mL of freshly distilled THF was added drop wise. The color of the reaction mixture changed to greenish brown. After stirring for a further period of 2 h at – 78° C, the reaction mixture was warmed gradually to room temperature. The reaction mixture was then poured into a saturated solution of NH4Cl and extracted with EtOAc. The organic phase was dried over anhydrous Na2SO4, filtered and evaporated to afford an oily compound which was purified by silica gel flash column chromatography eluting with 5 percent ethyl acetate in hexane to yield pure 2,5-dihydro-3,6-dimethoxy-2-isopropyl-5- (2′-iodo-4′,5′-dibenzyloxybenzyl)-(2R,5S)-pyrazine (32) as a white solid in 70percent yield.

The synthetic route of (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; SATYAMURTHY, Nagichettiar; BARRIO, Jorge, R.; WO2010/117435; (2010); A2;,
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. 14508-49-7, name is 2-Chloropyrazine, A new synthetic method of this compound is introduced below., Formula: C4H3ClN2

Example 189a tert-Butyl 4-(Pyrazin-2-yl)piperazine-1-carboxylate 189a A 500-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with DMSO (250 mL), tert-butyl piperazine-1-carboxylate (15.8 g, 85.0 mmol), 2-chloropyrazine (9.7 g, 85.0 mmol), and Cs2CO3 (55.3 g, 170 mmol). The mixture was heated at 60C for 3 days. After this time the reaction was cooled to room temperature. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 5:1 petroleum ether/ethyl acetate to afford 189a (13.3 g, 60 %) as a yellow solid. MS: [M+H]+ 265.3

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; F.Hoffmann-La Roche AG; CRAWFORD, James John; ORTWINE, Daniel Fred; WEI, BinQing; YOUNG, Wendy B.; EP2773638; (2015); B1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 113305-94-5, A common heterocyclic compound, 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, molecular formula is C5H4N4, 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.

Synthesis 23-1 -B 5-(1 H-Pyrrolo[2,3-c]pyridin-5-ylamino)pyrazine-2-carbonitrile (CC-001 ) A mixture of tert-butyl 5-chloro-1 H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.030 g, 0.119 mmol), 5-aminopyrazine-2-carbonitrile (0.017 g, 0.142 mmol), cesium carbonate (0.077 g, 0.237 mmol), Xantphos (0.011 g, 0.019 mmol) and tris(benzylideneacetone)dipalladium (0) (0.009 g, 0.010 mmol) in dioxane (0.8 mL) was degassed by bubbling argon through the mixture for 10 minutes. The sealed reaction vessel was heated to 150C for 1 hour in a microwave reactor. The crude mixture was filtered through an SCX-2 acidic resin cartridge, eluting with 2 M ammonia in methanol. The basic filtrate was concentrated and purified by column chromatography to give the title compound (0.018 g, 0.054 mmol, 45%). LC-MS (3) Rt = 1.30 min; m/z (ESI+) 237 (M+H).

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

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; WO2009/103966; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 16298-03-6, 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. 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 157A Methyl 3-bromopyrazine-2-carboxylate To a rapidly stirring heterogeneous mixture of 3-aminopyrazine-2-carboxylic acid methyl ester (2.00 g, 13.1 mmol) in 48% hydrobromic acid (7.9 mL) cooled to 0 C. was added bromine (2.00 mL, 6.2 g, 38.8 mmol) dropwise over 5 minutes. Then a solution of sodium nitrite (2.27 g, 32.8 mmol) in 9.5 mL of water was added dropwise over 10 minutes. The reaction mixture was stirred at 0 C. for 15-30 minutes and then basified with 60 mL of saturated sodium bicarbonate solution and extracted with ethyl acetate followed by chloroform. The combined organic extracts were dried over magnesium sulfate and concentrated under reduced pressure. The residue obtained was flash chromatographed on silica gel eluding with mixtures of hexane and ethyl acetate to afford the title compound (1.265 g, 46%). m.p. 43.5-44 C. 1 H NMR (CDCl3, 300 MHz) delta 4.04 (s, 3H), 8.50 (bs, 1H), 8.60 (bs, 1H). MS (DCl/NH3) m/e 217/219 (M+H)+, 234/236 (M+H+NH3)+.

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 2-aminopyrazine-3-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Abbott Laboratories; US5250548; (1993); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 5521-55-1, 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. 5521-55-1 name is 5-Methylpyrazine-2-carboxylic acid, 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.

General procedure: To a solution of R1COOH (1mmol) in DMF (5ml), DIEA (3mmol), intermediate 3 (1.1mmol) and HBTU (1mmol) were added at room temperature for 10h. The mixture was diluted with 20ml water and extracted with ethyl acetate (3×20ml). The combined organic layers were washed with saturated aqueous sodium bicarbonate and brine, and then dried over anhydrous sodium sulfate. After removing the solvent under reduced pressure, the crude product was purified by flash chromatography on silica gel, eluting with dichloromethane/methanol (2-5%), yield 70-95%.

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

Reference:
Article; Yao, Dahong; Zhou, Yuxin; Zhu, Lingjuan; Ouyang, Liang; Zhang, Jin; Jiang, Yingnan; Zhao, Yuqian; Sun, Dejuan; Yang, Shilin; Yu, Yang; Wang, Jinhui; European Journal of Medicinal Chemistry; vol. 140; (2017); p. 155 – 171;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 4430-75-5,Some common heterocyclic compound, 4430-75-5, name is Octahydro-2H-pyrido[1,2-a]pyrazine, molecular formula is C8H16N2, 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.

DIPEA (71 mg, 00.1 mL, 0.55 mmol) was added to a stirred solution of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylic acid (75 mg, 0.22 mmol) in DMF (1.5 mL) followed by addition of EDCl (63 mg, 0.33 mmol) and HOBt (32 mg, 0.24 mmol). After 10 minutes of stirring the reaction mixture, octahydro-1H-pyrido[1,2-a]pyrazine (46 mg, 0.33 mmol) was added and the resulting mixture was stirred for 16 h at 20-35 C. The reaction mixture was diluted with cold water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine solution. The ethyl acetate portion was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the crude compound, which was refluxed in hexane, filtered, and the filtrate was concentrated under reduced pressure to afford 45 mg of the title compound as a yellow solid. MS (ESI): m/z 466.3 (M+H).

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

Reference:
Patent; DR. REDDY’S LABORATORIES LTD.; Sasmal, Pradip Kumar; Ahmed, Shahadat; Prabhu, Ganesh; Tehim, Ashok; Paradkar, Vidyadhar; Dattatreya, Marahanakuli Prasanna; Mavinahalli, Nanjegowda Jagadeesh; US2015/5280; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. Product Details of 87486-34-8

Example 307c 5-Bromo-3-(1,3-dimethyl-1H-indazol-5-ylamino-1-methylpyrazin-2(1H)-one 307c To a solution of 307b (280 mg, 1.74 mmol) in i-propanol (7 mL) was added triethylamine (352 mg, 3.48 mmol) and 3,5-dibromo-1-methylpyrazin-2(1H)-one (H-005) (700 mg, 2.61 mmol). After being stirred at reflux for 6 h, the mixture was cooled to room temperature. The precipitate was filtered, washed with i-propanol (2 X 2 mL), and dried at 60°C under reduced pressure to afford 307c as a brown solid (560 mg, 92percent). MS-ESI: [M+H]+ 347.8.

The synthetic route of 3,5-Dibromo-1-methylpyrazin-2(1H)-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F.Hoffmann-La Roche AG; CRAWFORD, James John; ORTWINE, Daniel Fred; WEI, BinQing; YOUNG, Wendy B.; EP2773638; (2015); B1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem