Month: March 2021

Synthetic Route of 113305-94-5, These common heterocyclic compound, 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, 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 tert-butyl 4-((2-chloro-5-iodopyridin-4-ylamino)methyl)piperidine-1- carboxyiate (Synthesis 170-B) (0.100 g, 0.22 mmol), dichlorobis(triphenyiphosphine)- palladium (II) (0.009 g, 0.01 mmol), trimethyl(2-methylbut-3-yn-2-yloxy)silane (0.048 mL, 0.24 mmol) and copper iodide (0.002 g, 0.01 mmol) was heated under microwave irradiation for 5 min at 120 0C. The crude mixture was concentrated in vacuo and filtered through a pad of silica, eluting with hexane / ethyl acetate (8 / 2), to give the crude product which was used without further purification. The crude pyridine (0.085 g, 0.163 mmol), 2-amino-4-cyanopyrazine (0.023 g, 0.195 mmol), Xantphos (0.015 g, 0.026 mmol), cesium carbonate (0.106 g, 0.326 mmol), dichlorobis(triphenylphosphine)- palladium (II) (0.012 g, 0.013 mmol) in dioxane (1.2 mL) were stirred at room temperature under nitrogen for 10 min, then heated under microwave irradiation for 60 min at 150 CC. The reaction mixture was purified by ion exchange on SCX-II acidic resin (2 g), eluting with methanol / dichloromethane (1 / 1 ), then 2M ammonia-methanol. The basic fractions were combined and solvent was removed in vacuo. The crude product was purified by preparative thin layer chromatography, eluting with methanol / dichloromethane (1 / 19), to give the title compound as a yellow solid (0.024 g, 27%).1H NMR (CDCI3, 500 MHz) delta 8.62 (s, 1 H), 8.44 (s, 1 H), 8.00 (s, 1 H), 7.17 (s, 1 H), 5.19 (t, 1 H, J = 5.8 Hz) 4.19-4.16 (m, 2H), 3.17 (t, 2H, J = 6.1 Hz), 2.72 (t, 2H, J = 11.3 Hz), 1.84- 1.75 (m, 3H), 1.66 (s, 6H), 1.47 (s, 9H), 1.27-1.21 (m, 2H), 0.90-0.84 (m, 1 H). LCMS (4) Rt = 2.17 min; m/z (ESI+) 492 [MH+].

Statistics shows that 5-Aminopyrazine-2-carbonitrile is playing an increasingly important role. we look forward to future research findings about 113305-94-5.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; WO2009/44162; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 25911-65-3,Some common heterocyclic compound, 25911-65-3, name is 3-Aminopyrazine-2-carbonitrile, molecular formula is C5H4N4, 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.

d) 4-Amino-2-[(2,2,2-trifluoroethoxy)methyl]pteridine Obtained using the procedure described in section c of Example 2, starting with 7.2 g (0.060 mole) of 3-amino-2-pyrazinecarbonitrile and 14.2 g (0.091 mole) of 2-(2,2,2-trifluoroethoxy)acetamidine in 230 ml of absolute ethanol. Refluxing time: 7 hours. Yld: 6.5 g (42%), m.p. 145-147 C. (ethyl acetate). NMR (DMSO-d6): delta=4.2 (2H, q); 4.6 (2H, s); 8.3 (2H, peak exchangeable with CF3 COOD); 8.7 (1H, m); 9.0 (1H, m).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Aminopyrazine-2-carbonitrile, its application will become more common.

Reference:
Patent; Lipha, Lyonnaise Industrielle Pharmaceutique; US5167949; (1992); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 87486-34-8, name is 3,5-Dibromo-1-methylpyrazin-2(1H)-one, 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 87486-34-8, category: Pyrazines

Example 112 CGI PHARM6 0WO5-Bromo-l-methyl-3-(pyridin-3-ylamino)pyrazin-2(lH)-one 112a112aA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer, reflux condenser and nitrogen inlet was charged with THF (15 mL), 3,5-dibromo-l-methylpyrazin- 2(lH)-one (1.00 g, 3.73 mmol), 3-aminopyridine (351 mg, 3.73 mmol) and sodium tert- butoxide (789 mg, 8.21 mmol). After bubbling nitrogen through the resulting solution for 30 min, Pd2Br2(t-Bu3P)2 (29 mg, 0.037 mmol) was added, and the reaction mixture was stirred at room temperature for 2.5 h. After this time the reaction was partitioned between ethyl acetate (50 mL) and water (50 mL) and filtered. The aqueous layer was separated and extracted with ethyl acetate (2 x 25 mL). The organic layers were combined, washed with brine (50 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate concentrated under reduced pressure. The resulting residue was purified by column chromatography to afford a 35percent yield (370 mg) of 112a as a brown solid: mp >250¡ãC; ]H NMR (500 MHz, DMSO- 6) delta 9.75 (s, 1H), 9.08 (d, 1H, / = 2.5 Hz), 8.32 (m, 1H), 8.24 (dd, 1H, / = 5.0, 1.5 Hz), 7.40 (s, 1H), 7.36 (dd, 1H, J = 8.5, 4.5 Hz), 3.45 (s, 3H); MS (APCI+) m/z 281.0 (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; GILEAD CONNECTICUT, INC.; GENENTECH, INC.; CURRIE, Kevin S.; WANG, Xiaojing; YOUNG, Wendy B.; WO2012/31004; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

23688-89-3, name is 6-Chloropyrazine-2-carboxylic acid, 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. HPLC of Formula: C5H3ClN2O2

Example 41 6-chloro-N-(2-methoxy-1-(4 (trifluoromethoxy)phenyl)ethyl)pyrazine-2-carboxamide A mixture of 6-chloropyrazine-2-carboxylic acid (150 mg), thionyl chloride (0.345 mL), N,N-dimethylformamide (0.05 mL) and toluene (5 mL) was stirred at 100C for 1 hr. The mixture was concentrated under reduced pressure, to the residue were added tetrahydrofuran (5 mL), triethylamine (0.659 mL) and 2-methoxy-1-(4-(trifluoromethoxy)phenyl)ethanamine hydrochloride (257 mg), and the mixture was stirred at room temperature for 5 hr. The mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (225 mg). 1H NMR (300 MHz, CDCl3) delta 3.43 (3H, s), 3.77 (2H, d, J = 4.9 Hz), 5.23-5.46 (1H, m), 7.13-7.25 (2H, m), 7.39-7.53 (2H, m), 8.27 (1H, d, J = 7.5 Hz), 8.77 (1H, s), 9.27 (1H, s).

The synthetic route of 23688-89-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; SETO, Masaki; BANNO, Yoshihiro; IMAEDA, Toshihiro; KAJITA, Yuichi; ASHIZAWA, Tomoko; KAWASAKI, Masanori; NAKAMURA, Shinji; MIKAMI, Satoshi; NOMURA, Izumi; TANIGUCHI, Takahiko; MARUI, Shogo; (153 pag.)EP3061754; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 5521-56-2, name is 6-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 5521-56-2, name: 6-Methylpyrazin-2-amine

Compound 10: 5-Bromo-6-methyl-pyrazin-2-ylamine. Under inert condition, to a solution 6-amino-2-methylpyrazine (100 mg, 1.0 equiv.) in a mixture of DMSO (4.6 mL) and water (0.2 mL) cooled by an ice bath, NBS (179 mg, 1.1 equiv.) was added in 3 portions. The light yellow mixture was stirred for 15 minutes, and then for 5 hrs at room temperature. The reaction mixture was hydrolysed with NaHCO3 saturated solution (25 mL) and extracted with EtOAc (30 mL). The organic layer was washed with brine, dried over Na2SO4 and concentrated. Purification by flash-chromatography afforded compound 10 as a light yellow solid in 36% yield. 1H-NMR (400 MHz, DMSO): 2.34 (bs, 3H, C-CH3); 6.52 (bs, 2H, NH2); 7.49 (s, 1H, Ar). M/Z (M[79Br]+H)+ = 188.2.

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, 6-Methylpyrazin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Domain Therapeutics; Mayer, Stanislas; Schann, Stephan; EP2666775; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 75907-74-3, name is (3,5,6-Trimethylpyrazin-2-yl)methanol, 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 75907-74-3

Compound 1a (6.08 g, 40 mmol) was dissolved in CHCl3 (60 mL),MnO2 (24 g, 280 mmol) was added, and the mixture was refluxed for 6 h, cooled, filtered, and concentrated. The crude productwas purified by column chromatography and eluted with ethyl acetate-petroleum ether (1:6) to yield 1b as bright yellowcrystals (4.2 g, 70%), mp 86C. ESI-MS m/z 151 [M + 1]+, C8H10N2O. 1H NMR (500 MHz, CDCl3, , ppm): 10.10 (1H, s,CHO), 2.75 (3H, s, CH3), 2.56 (6H, s, CH3 2). 13C NMR (125 MHz, CDCl3, , ppm): 21.39, 22.18, 141.91, 149.98, 151.54,155.45, 194.33.

The synthetic route of (3,5,6-Trimethylpyrazin-2-yl)methanol has been constantly updated, and we look forward to future research findings.

Reference:
Article; Zhang, Chao; Chen, Lang-Di; Liang, Xin-Tong; Liu, Wei-Xiong; Wu, Wen-Hao; Chemistry of Natural Compounds; vol. 53; 1; (2017); p. 114 – 117; Khim. Prir. Soedin.; vol. 53; 1; (2017); p. 96 – 98,3;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 944709-42-6, name is 6,8-Dibromo-[1,2,4]triazolo[1,5-a]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. Quality Control of 6,8-Dibromo-[1,2,4]triazolo[1,5-a]pyrazine

A flask equipped with a mechanical stirrer was charged with 6,8-dibromo-[1,2,4]triazolo[1,5-a]pyrazine (63.9 g, 230 mmol) and DMF (700 mL) followed by(1r,4r)-4-(4-amino-1H-pyrazol-1-yl)cyclohexanol (41.7 g, 230 mmol) and N-ethyl-N-isopropylpropan-2-amine (80 mL, 460 mmol). The reaction mixture was stirred at ambient temperaturefor 16 h. The reaction mixture was diluted with water (1.5 L) and filtered. The collectedsolid was triturated with water to give the title compound (84.0 g, 97percent); MS m/z: 378,380 (M+H)+; 1H NMR (400 MHz, DMSO-d6) delta 10.63 (s, 1H), 8.54 (d, J = 5.6 Hz, 1H), 8.07 (s, 1H),7.76 (s, 1H), 4.61 (d, J = 4.3 Hz, 1H), 4.20¡À4.05 (m, 1H), 3.48 (dq, J = 10.7, 5.6, 5.1 Hz, 1H),2.08¡À1.85 (m, 4H), 1.85¡À1.64 (m, 2H), 1.43¡À1.19 (m, 2H).

The synthetic route of 6,8-Dibromo-[1,2,4]triazolo[1,5-a]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Article; George, Dawn M.; Huntley, Raymond J.; Cusack, Kevin; Duignan, David B.; Hoemann, Michael; Loud, Jacqueline; Mario, Regina; Melim, Terry; Mullen, Kelly; Somal, Gagandeep; Wang, Lu; Edmunds, Jeremy J.; PLoS ONE; vol. 13; 9; (2018);,
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. 4858-85-9, name is 2,3-Dichloropyrazine, This compound has unique chemical properties. The synthetic route is as follows., Safety of 2,3-Dichloropyrazine

A thick-walled reaction vessel (250 mL) charged with 2, 3-dichloropyrazine (14.9 g, 95 mmol) and 28-30% ammonium hydroxide (75 mL) was sealed in vacuo, submitted to a freeze-pump- thaw cycle and then heated with stirring to 135 C for 15 h. Upon cooling of the reaction mixture, needles were observed to form from the reaction mixture. The supernatant was decanted off and the residual solid was solubilized in hot methanol. The methanol solution was concentrated in vacuo and the resultant crude material (10. 8 g) was recrystallized from methanol (150 mL) to yield 8.26 g of the title compound (67% yield). mp 167-168 C ; Rf 0.5 (EtOAc-hexanes, 1 : 1, v/v, +0.5% v/v iPrNH2) ;’H NMR (DMSO-d6) 8 8.9 (s, 1H), 8. 7 (s, 1H), 5.0 (br s, 2H)

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 4858-85-9.

Reference:
Patent; CARDIOME PHARMA CORPORATION; WO2005/34837; (2005); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 69214-33-1, name is 8-Chloroimidazo[1,2-a]pyrazine, molecular formula is C6H4ClN3, 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. HPLC of Formula: C6H4ClN3

To a solution of the product form step 2 (82.9 mg, 0.29 mmoi) in DMF (5 mL) was added NaH (14.0 mg 0.35 mrnol, 60 wt% in oil) at RT. The mixture was stirred at RT for 30 minutes, then 8.-chloroirnidazo[I2.-a]pyrazine (45.9 mg, 0.30 mmol) was added. The resulting mixture was heated to 40C for 2.5 hr. After cooling to RT, the mixture was poured into water (5 mL) and extracted with EtOAc (5 mL x 3). The combined organic layer was washed with brine, driedover MgSO4, filtered and concentrated in vacuo. The residue was purified by Prep-HPLC to afford the title compound (60 mg) as a brown solid. LRMS mz (M+H) 404,1 found, 404.1 required.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 69214-33-1, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIVERTON, Nigel; KUDUK, Scott D.; BESHORE, Doug C.; MENG, Na; LUO, Yunfu; (127 pag.)WO2016/101119; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 75907-74-3, name is (3,5,6-Trimethylpyrazin-2-yl)methanol, 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. Recommanded Product: 75907-74-3

The obtained 2-hydroxymethyl-3,5,6-trimethylpyrazine (152 mg, 1 mmol) was dissolved in a THF solution, and phosphorus tribromide (410 mg, 1.5 mmol) was added dropwise under an ice bath condition. The reaction was stirred at 0 C for 30 minutes, and the reaction was quenched by adding saturated sodium bicarbonate. Dilute with 50ml of ethyl acetate, and wash the organic layer three times with saturated brine, dry over anhydrous sodium sulfate, filter, and concentrate, silica gel column chromatography (petroleum ether: ethyl acetate = 2: 1)2-bromomethyl-3,5,6-trimethylpyrazine was obtained as a light yellow solid (182 mg, 85%).

The synthetic route of (3,5,6-Trimethylpyrazin-2-yl)methanol has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Taizhou College; Mu Yi; Zhang Rui; Liu Jing; Gao Xinxing; (8 pag.)CN110483419; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem