Month: April 2021

Adding a certain compound to certain chemical reactions, such as: 113305-94-5, name is 5-Aminopyrazine-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 113305-94-5, Formula: C5H4N4

EXAMPLE 12 (?)-5-((4-Amino-8-(4-(2-cyanovinyl)-2,6-dimethylphenyl)quinazolin-2- yI)amino)pyrazine-2-carbonitrile- Compound 12 Synthesis of (?)-5-((4-amino-8-(4-(2-cyanovinyI)-2,6-dimethyIphenyl)quinazolin-2- yl)amino)pyrazine-2-carbonitrile (compound 12) [0274] Compound 2a (20 mg, 0.06 mmol), 5-aminopyrazine-2-carbonitrile (22 mg, 0.18 mmol, Ark Pharm Inc, AK-21935), N,N-diisopropylethylamine (62 mg, 0.47 mmol), (9,9- dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (3 mg, 0.006 mmol) and palladium (II) acetate (1 mg, 0.006 mmol) were combined under argon in N-methyl-2-pyrrolidone (1 mL). The reaction was heated at 120C in a sealed vessel for 3 hours. The reaction mixture was cooled down to room temperature and purified by reverse phase chromatography (0- 100% acetonitrile in water with 0.1% trifluoroacetic acid) to afford the TFA salt of compound 12. NMR (400 MHz, DMSO- 6) delta 8.98 (bs, 1 H), 8.36 (bs, 1 H), 7.85 – 7.28 (m, 6H), 6.59 (d, J = 15.6 Hz, 1H), 1.94 (s, 6H). LCMS (m/z) 419.3 [M+H], Tr = 1.89 min (LCMS method 2).

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

Reference:
Patent; GILEAD SCIENCES, INC.; INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY OF THE AS CR, V.V.I.; JANSA, Petr; SIMON, Tetr; LANSDON, Eric; HU, Yunfeng, Eric; BASZCZYNSKI, Ondrejj; DEJMEK, Milan; MACKMAN, Richard, L.; (185 pag.)WO2016/105564; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 875781-43-4, These common heterocyclic compound, 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]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.

A solution of 21 (100 mg, 0.507 mmol) and 2 (84 mg, 0.507 mmol) in toluene and ethanol (4:1 mL) was added Na2CO3 (111.01 mg, 1.014 mmol). The reaction was degassed and purged with nitrogen for 10 min. Pd(dppf)Cl2 (20.7 mg, 0.025 mmol) was added to the reaction. The reaction was degassed and purged with nitrogen for another 10 min. The reaction was heated to 90 C. under sealed condition overnight, allowed to cool to RT, and diluted with chloroform. The organic layer was filtered through Celite and concentrated to get the crude, which was purified through flash chromatography by using 100-200 mesh silica gel. The compound was eluted in 40% ethyl acetate in hexane as an off-white solid 22. MS-ES+ 264.8; 1H NMR (400 MHz, DMSO-D6) 22: 9.99 (bs, 1H), 9.40 (bs, 1H), 7.25 (bs, 1H), 7.08 (m, 1H), 7.00 (d, 1H), 6.42 (m, 2H), 6.21 (m, 1H), 5.71 (m, 1H).

Statistics shows that 2-Bromo-5H-pyrrolo[2,3-b]pyrazine is playing an increasingly important role. we look forward to future research findings about 875781-43-4.

Reference:
Patent; ARRIEN PHARMACEUTICALS LLC; Vankayalapati, Hariprasad; Yerramreddy, Venkatakrishnareddy; Gangireddy, Paramareddy; Appalaneni, Rajendra P.; US2014/315909; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 723286-80-4, A common heterocyclic compound, 723286-80-4, name is tert-Butyl 3-bromo-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxylate, molecular formula is C10H15BrN4O2, 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.

Preparation 154: 3-bromo-5,6,7,8-tetrahydro-[1 ,2,4]triazolo[4,3-a]pyrazine To a solution of ie/i-butyl 3-bromo-5,6-dihydro-[1 ,2,4]triazolo[4,3-a]pyrazine- 7(8H)-carboxylate (52 mg, 0.172 mmol) in DCM (6 mL) at 0C was added TFA (0.26 mL). The reaction was stirred at room temperature for 16 hours before concentrating in vacuo. The residue was purified by elution through an SCX-2 column using 2M NHs/MeOH to give the title compound as yellow solid (29 mg, 83%). 1 H NMR (500 MHz, MeOD): delta 4.10 (s, 1 H), 3.93 (t, J = 5.63 Hz, 2H), 3.25 (t, J = 5.63 Hz, 2H). LCMS (ESI) Rt = 0.40 minutes MS m/z 203 [M79Br+H]+

The synthetic route of 723286-80-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; HOELDER, Swen; BLAGG, Julian; CHEUNG, Jack; ATRASH, Butrus; SHELDRAKE, Peter; WO2014/37751; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 16298-03-6, These common heterocyclic compound, 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, 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.

Step B: Methyl 3-[(4-methyl-1-naphthoyl)amino]pyrazine-2-carboxylate; At 90 ¡ãC a solution of 4-methyl-1-naphthalenecarbonyl chloride (12 mmol) in CH2CICH2CI (20 mL) was slowly added into a solution of methyl 3-aminopyrazine-2- carboxylate (1.53 g, 10.0 mmol) and DMAP (100 mg) in CH2CICH2CI (100 mL) and pyridine (10 mL) during a period of six hours. The resulting reaction mixture was stirred at the same temperature overnight, and was then condensed, and extracted by EtOAc, washed by brine, dried over MgS04. Removal of solvents provided a crude product, which was purified by flash silica gel column using heptane/EtOAc (10: 0 to 0: 10) to give the title product as a solid (1.5 g, 47 percent) : 1H NMR (400 MHz, CDC13) No. 1H NMR (400 MHz, CD30D) 2.77 (s, 3H), 3.94 (s, 3H), 7.46 (d, J=8.0 Hz, 1H), 7.60 (m, 2H), 7.79 (d, J=8.0 Hz, 1H), 8.14 (d, J=8.0 Hz, 1H), 8.42 (m, lH), 8.50 (m, 1H), 8.64 (m,lH).

The synthetic route of 16298-03-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AstraZeneca AB; WO2005/115986; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 762240-92-6,Some common heterocyclic compound, 762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, molecular formula is C6H8ClF3N4, 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 1: Preparation of tert-butyl (R)-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-alpha]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)-4-oxobutan-2-ylcarbamate (Compound of formula 2 wherein R is Boc) [35] (R)-3-Boc-amino-4-(2,4,5-trifluorophenyl)-butanoic acid (3.0g, 9.0mmol) and tetrahydrofuran (THF, 30ml) were charged and dissolved in a dry flask, and N-methylmorpholine (2.97ml, 27.0mmol) was added thereto. Then, the mixture was cooled to a temperature of 0 to 5C, and 2-chloro-4,6-dimethoxy-1,3,5-triazine (2.05g, 11.7mmol) was added thereto. After being stirred at a temperature of 0 to 5C for one hour, 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-alpha]pyrazine hydrochloride (2.47g, 10.8mmol) was added and the reaction mixture was stirred while elevating to a temperature of 20 to 25C. After the completion of the reaction was confirmed by TLC, the reaction liquid was cooled to 10C, and dichloromethane (30.0ml) and water (30.0ml) were added thereto, followed by separation of layers. The organic layer was washed with saturated sodium bicarbonate (30.0ml) and saline (30.0ml), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then crystallized from ethyl acetate (12.0ml) and isopropyl alcohol (6.0ml) to afford 4.29g (yield: 94.0%) of tert-butyl (R)-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-alpha]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)-4-oxobutan-2-ylcarbamate.[36] 1H NMR delta 7.04(dd, 1H, J=0.012), 6.84(dd, 1H, J=0.013), 5.01(s, 2H), 4.90(NH), 4.20(s, 2H), 4.10(t, 2H), 4.04(t, 2H), 3.97(m, 1H), 2.97(t, 2H), 2.70(t, 2H),[37] mp: 183.0 to 183.5C (as measured using a capillary melting point apparatus Mettler FP90 at an elevation rate of 2C/min)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, its application will become more common.

Reference:
Patent; ST PHARM CO., LTD.; LIM, Geun Gho; CHANG, Sun Ki; BYEON, Chang Ho; WO2012/99381; (2012); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 5424-01-1, name is 3-Aminopyrazine-2-carboxylic acid, molecular formula is C5H5N3O2, 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. Formula: C5H5N3O2

Add 3-aminopyrazine-2-carboxylic acid (50.0 g, 369.4 mmol) to a solution of N-bromosuccinimide (61.2 g, 377.3 mmol) and dimethylformamide (236.3 g, 3.2 mole) at 0 C. After 1 hour at room temperature, an orange solid is formed. Wash the solid residue with ethyl acetate (500 mL) and discarded it. Dry the organic phase with sodium sulfate, filter, and concentrate under reduced pressure to yield the title compound as a white solid (32.0 g, 146.7 mmol, 41%). ES/MS m/z (79Br/81Br) 217.1/219.0 (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 5424-01-1, its application will become more common.

Reference:
Patent; ELI LILLY AND COMPANY; CIFUENTES-GARCIA, Marta Maria; GARCIA-PAREDES, Maria Cristina; (34 pag.)WO2018/194885; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

109-08-0, name is 2-Methylpyrazine, 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. Recommanded Product: 109-08-0

(1) Dissolve 9.41 g (0.1 mol) of 2-methylpyrazine in 30.0percent of 182.30 g of hydrochloric acid (containing 1.5 mol of hydrogen chloride).Under stirring, the temperature was controlled at 0-15¡ãC, and 25.32 g of a 25.0percent hydrogen peroxide solution was added dropwise.The reaction temperature was controlled at 0-15¡ãC to make the reaction system chlorinated. The reaction was sampled at regular intervals and detected by high performance liquid chromatography.When it was detected that the mass of 2-methyl-3-chloropyrazine in the reaction system accounted for 73.5percent of the total organic matter mass in the reaction system,The reaction was terminated by adding 17.21 g (0.12 mol) of cuprous bromide to obtain a 2-methyl-3-chloropyrazine-containing solution; (2) Add 63.78 g of methylene chloride to the feed solution, stir and extract for 2 hours, and let stand for 1 hour.Take the organic phase and allow it to cool down to -15¡ãC to -5¡ãC to allow solids to be analyzed from the organic phase.8.36 g of the resulting fixative is 2-methyl-3-chloropyrazine,After calculation, the yield was 65.5percent, and the main containment was 97.8percent.

The synthetic route of 109-08-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shandong Tianxin Chemical Co., Ltd.; Ju Youguo; Zhao Benteng; Wang Zewu; Yang Hanhua; Zhang Zhaoyuan; Liu Jian; Gong Fangxin; (6 pag.)CN107954913; (2018); A;,
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. 369638-68-6, name is tert-Butyl (5-methylpyrazin-2-yl)carbamate, This compound has unique chemical properties. The synthetic route is as follows., Safety of tert-Butyl (5-methylpyrazin-2-yl)carbamate

Intermediate: te/t-butyl 5-(bromomethyl)pyrazin-2-ylcarbamate (29b)BocHNgammaN.(29b)To a solution of te/t-butyl 5-methylpyrazin-2-ylcarbamate (29a) (100 g, 0.48 mol) inCCU (40 mL) was added NaHCO,? followed by AZ-bromosuccinimide (130 g, 0.57 mol). The resulting mixture was heated to reflux at 800C for 12 hours then cooled to room temperature. The reaction mixture was filtered through Cehte and the filtrate was concentrated in vacuo. The crude product was chromatographed (SiO?; 5 % EtOAc in CHCI3) to give tert-buty 5-{bromomethyi)pyrazm-2-y.carbamate (29b).

According to the analysis of related databases, 369638-68-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PFIZER INC.; BENBOW, John William; LOU, Jihong; PFEFFERKORN, Jeffrey Allen; TU, Meihua Mike; WO2010/13161; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 69816-35-9, 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. 69816-35-9, name is 6-(Trifluoromethyl)pyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows.

(a) 2-Iodo-6-trifluoromethylpyrazine A three liter flask was charged with a solution of 2-amino-6-trifluoromethylpyrazine (obtained by the method of J. L. Miesel, U.S. Pat. No. 4,293,552, 95% pure by HPLC analysis, 32.6 g, 0.20 mol) in chloroform (1000 mL). Freshly ground iodine (101 g. 0.40 mol) was added to give a dark purple solution. After 40 min, a solution of t-butyl nitrite (22.9 g, 0.20 mol) in chloroform (300 mL) was added dropwise over 1 h. During the addition, slow gas evolution was observed together with a mild exotherm (<10 C.) which was moderated with a cold water bath. After an additional 1 h at room temperature the reaction mixture was washed with saturated aqueous sodium sulfite (3*500 mL) to remove the excess iodine. The chloroform solution was dried over magnesium sulphate, filtered and concentrated on a Buchi to give 23 g of an orange oil. The crude product was purified by distillation from copper (40-80 mesh, 200 mg) to give 19.5 g of the title compound as a yellow oil; b.p. 50-56 C./0.6 mmHg; delta (360 MHz, CDCl3) 9.06 (1H, s, pyrazine-H), 8.86 (1H, s, pyrazine-H); m/e 274 (M+). The chemical industry reduces the impact on the environment during synthesis 6-(Trifluoromethyl)pyrazin-2-amine. I believe this compound will play a more active role in future production and life. Reference:
Patent; Merck Sharpe & Dohme Ltd.; US5384408; (1995); A;,
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. 138588-41-7, name is Pyrazine-2-carboximidamide hydrochloride, A new synthetic method of this compound is introduced below., Application In Synthesis of Pyrazine-2-carboximidamide hydrochloride

[0106] A mixture of diethyl 2-(2,4,6-trifluorophenyl)malonate (250 mg, 0.861 mmol), 2- pyrazinecarboxamidine hydrochloride (144 mg, 0.904 mmol, 1.05 equiv), and tributylamine (221 mu., [172 mg], 1.08 equiv) was stirred under nitrogen atmosphere at 180 C for 1 h in a sealed tube. The mixture was cooled to room temperature and treated with 1.0 N hydrochloric acid. The precipitates were collected by filtration, washed with water and dried to give 2-pyrazin-2-yl-5- (2,4,6-trifluorophenyl)pyrimidine-4,6-diol as a dark tan solid (163 mg), which was used directly in the next step. [0107] A mixture of 2-pyrazin-2-yl-5-(2,4,6-trifluorophenyl)pyrimidine-4,6-diol (163 mg) in phosphorous oxychloride (2.03 mL, 21.9 mmol, 43 equiv) and 2,6-lutidine (404 muIota_,, 3.51 mmol, 6.9 equiv) was heated at 1 10 C for 16 h in a sealed tube. The excess phosphorous oxychloride was removed in vacuo, and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with water and saturated sodium chloride, dried over sodium sulfate, and concentrated. The residue was purified by silica gel chromatography over silica gel, eluting with a gradient of 20% ethyl acetate in hexanes to 33% ethyl acetate in hexanes. Concentration provided 104 mg of the title compound as a light yellow solid (32% over two steps). -NMR (500 MHz; CDC13): delta 9.73 (s, 1H), 8.84 (s, 1H), 8.77 (s, 1H), 6.88-6.84 (m, 2H) ppm.

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; THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA; BALLATORE, Carlo; BRUNDEN, Kurt, R.; HOYE, Adam, T.; LEE, Virginia, M.y.; SMITH, Amos, B.; TROJANOWSKI, John, Q.; WO2014/47257; (2014); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem