Month: November 2020

486424-37-7, A common compound: 486424-37-7, name is 3-Amino-6-bromopyrazine-2-carboxylic acid, belongs to Pyrazines compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

1- (3-DIMETHYLAMINOPROPYL)-3-ETHYLCARBODIIMIDE hydrochloride (0.68 g, 3.5 mmol) was added in one portion to a stirred suspension of 2-MORPHOLIN-4-YLETHANAMINE (0.422 g, 3.2 mmol), 3-amino-6-bromopyrazine-2-carboxylic acid (0.64 g, 3.0 mmol; described in: Ellingson, R. C.; Henry, R. L. J. Am. Chem. Soc. 1949,2798-2800), and 1- hydroxybenzotriazole hydrate (0.48 g, 3.5 mmol) in acetonitrile (25 mL) at 0 C. The cooling bath was removed and stirring was continued at room temperature for 7 h. The solid was filtered off, washed with acetonitrile and purified by column chromatography on silica using methylene CHLORIDE/METHANOL/TRIETHYL amine, (95: 5: 0.1), to give 0.68 g (69% yield) of the title compound : 1H NMR (DMSO-d6, 400 MHz) 8 8.53 (m, 1 H), 8.34 (s, 1 H), 8.68 (br s, 2 H), 3.57 (t, J = 5 Hz, 4 H), 3.37 (q, J = 7 Hz, 2 H), 2.47 (q, J = 7 HZ, 2 I-, 2.40 (m, 4 H); MS (ES) M/Z 330 and 332 (M+1).

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-Amino-6-bromopyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ASTRAZENECA AB; WO2004/55009; (2004); 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. 19745-07-4, name is 2,5-Dichloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 19745-07-4

To an NMP (7.5 ml) solution of 1.51 g of 2,5-dichloropyrazine were added 2.00 g of 1-(t-butoxycarbonyl)piperazine and 2.00 g of potassium carbonate, followed by 1 hour of stirring under heating at 100¡ãC. The mixture was cooled to room temperature, and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and brine and then dried over anhydrous magnesium sulfate, and thereafter, the solvent was evaporated. The residue was purified by silica gel column chromatography (chloroform-methanol) to obtain 2.73 g of 2-chloro-5-(4-t-butoxycarbonylpiperazin-1-yl)pyrazine. Using this compound, 2-chloro-5-{4-[6-(3,4-dimethoxyphenyl)pyridine-2-carbonyl]piperazin-1-yl}pyrazine was obtained in a similar manner to Example 14 as colorless crystals.

The synthetic route of 19745-07-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; YAMANOUCHI PHARMACEUTICAL CO. LTD.; EP1396487; (2004); 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 5049-61-6 as follows. 5049-61-6

Reference Synthesis Example 5 3,5-Dibromopyrazin-2-amine (42) (known compound, Reference: P. Jeanjot, et al., Synthesis, 513-522 (2003)) To a solution of aminopyrazine (4l) (10.0 g, 105 mmol) in DMSO (200 mL) and water (5 mL) was added N-bromosuccinimide (39.3 g, 221 mmol) at room temperature, and the mixture was stirred for 23 hours. To the mixture was added water and the product was extracted with diethyl ether (300 mL*4). The combined organic extract was washed successively with water (400 mL*2) and brine (500 mL*2), followed by drying over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by column chromatography (silica gel 280 g, n-hexane/dichloromethane/ethyl acetate=5/4/1). The resulting solid was further purified by recrystallization (n-hexane/ethyl acetate) to give Compound 42 (17.3 g, 68.3 mmol, 64.9%) as a colorless solid. Rf=0.48 (n-hexane/dichloromethane/ethyl acetate=5/4/1); 1H NMR (400 MHz, CDCl3) delta 5.05 (s, 2H), 8.05 (s, 1H).

According to the analysis of related databases, 5049-61-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JNC CORPORATION; NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY; US2011/244481; (2011); 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. 19745-07-4, name is 2,5-Dichloropyrazine, This compound has unique chemical properties. The synthetic route is as follows., 19745-07-4

Example 23Preparation of N-(2- ( (JS, 2S)-2-\ 1 -(5 -chloropyrimidin-2-yl)piperidin-4-yl] cyclopropyl } ethyl)-5 -( 1 H- 1 ,2,4-triazol- 1 -yl)pyrazin-2-amine,Step 1: 2-cMoro-5-flH–l.,2,4-triazol-1-yl’)pyrazine.2,5-Dichloropyrazine (298mg, 2.0mmol) and 1,2,4-triazole (145mg, 2.1mmol) were added in DMF (1OmL), then cesium carbonate was added and the reaction was at room temperature over night. Water (2OmL) was added, extracted with ethyl acetate (3OmL), second wash with brine (2OmL). The organic phase was dried by magnesium sulfate, filtered, concentrated and purified by column chromatography through a 25 gram Biotage SNAP KP-Sil.(TM). silica gel cartridge eluting with 22percent ethyl acetate/hexanes to give the title compound as a white solid.LRMS calc: 181.58; obs: 182.21(M+1).

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; MERCK SHARP & DOHME CORP.; WOOD, Harold, B.; ADAMS, Alan, D.; SZEWCZYK, Jason, W.; ZHANG, Yong; YANG, Meng; WO2011/19538; (2011); 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. 3149-28-8, name is 2-Methoxypyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 3149-28-8

General procedure: A magnetically stirred solution of xanthate (2.0 equiv) and pyrazine (1.0 equiv) in 1, 2-dichloroethane (1.0mmol/mL according to the xanthate) was refluxed for 15min under a flow of nitrogen. Then dilauroyl peroxide (DLP) was added portionwise (20mol % according to the xanthate) every hour until total consumption of one substrate. The reaction mixture was then cooled to room temperature and the solvent was evaporated under reduced pressure. Unless otherwise specified, the crude product was purified by flash chromatography on silica gel.

The synthetic route of 3149-28-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Huang, Qi; Qin, Ling; Zard, Samir Z.; Tetrahedron; vol. 74; 40; (2018); p. 5804 – 5817;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 6164-79-0, name is Methyl 2-pyrazinecarboxylate, 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. 6164-79-0

The 4- (3-CHLORO-4- (2-PYAZINYLMETHOXY) anilino) -5-fluoroquinazoline used as starting material was obtained as follows: Methylpyrazine carboxylate (8.5g) was stirred in water (200 ml) and sodium borohydride (11.65 g) was added in one portion, resulting in a vigorous exotherm. The reaction mixture was stirred vigorously for 30 minutes, and then ethanol (80 ML) and saturated potassium carbonate (150 ml) were added. The mixture was stirred for 30 minutes and then extracted with ethyl acetate (5 x 150 ml) and DCM (5 x 150 ml). The combined extracts were dried and concentrated to give pyrazin-2-ylmethanol as a yellow oil (5.43 g, 80%), which was used without purification; NMR spectrum (DMSO-D6) 4.65 (s, 2H), 5.57 (br s, 1H), 8.54 (d, 2H), 8.71 (s, 1H).

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 6164-79-0.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2004/93880; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

1458-18-0, Name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, 1458-18-0, 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.

The mixture of methyl 3-amino-5, 6-dichloropyrazine-2-carboxylate (4.4 g, 19.91 nMol) , 2- (4-fluorophenyl) -4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane (3.07 g, 21.9 nMol) in dioxane (50 mL) and water (5 mL ) was added Na 2CO 3 (4.22 g, 39.82 nMol) and dppfPdCl 2 (2.84 g, 3.98 nMol) . Then the mixture was stirred at 100 for 1 h under N 2 atmosphere. Then the mixture was concentrated and residue was poured to water (100 mL) and then extracted with EA (100 mL x 3) . The organic solution was then concentrated to afford the crude product (5.5 g, 98%yield) as a yellow solid which was used for next step without further purification. MS m/z (ESI) [M+H] + = 282.2.

Statistics shows that Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate is playing an increasingly important role. we look forward to future research findings about 1458-18-0.

Reference:
Patent; DIZAL (JIANGSU) PHARMACEUTICAL CO., LTD.; QI, Changhe; TSUI, Honchung; ZENG, Qingbei; YANG, Zhenfan; ZHANG, Xiaolin; (399 pag.)WO2020/35052; (2020); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

767340-03-4, Name is (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine, 767340-03-4, 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.

Into a flask was charged [Rh(cod)2]OTf (0.1 mmol) and (S) -Cy2-p-Tol-Biphemp (Ligand E) (0.1 mmol) under a nitrogen atmosphere. Degassed trifluoroethanol was then added (20 mL) and the mixture was stirred at room temperature for 1 h. Into a hydrogenator was charged the enamine amide 2-4 (1 mmol) and then degassed. The catalyst solution was then transferred to the hydrogenator under nitrogen. After degassing three times, the enamine amide was hydrogenated under 100 psig hydrogen gas at 20 ¡ãC for 20 h (94percent assay yield, 98percent ee). 1H NMR (300 MHz, CD3CN): No. 7.26 (m), 7.08 (m), 4.90 (s), 4.89 (s), 4.14 (m), 3.95 (m), 3.40 (m), 2.68 (m), 2.49 (m), 1.40 (bs). Compound 2-5 exists as amide bond rotamers. Unless indicated, the major and minor rotamers are grouped together since the carbon-13 signals are not well resolved: 13C NMR (CD3CN): 8 171.8,157.4 (ddd , JCF = 242.4,9.2, 2.5 Hz), 152.2 (major), 151.8 (minor), 149.3 (ddd; JCF = 246.7, 14.2,12.9 Hz), 147.4 (ddd, JCF = 241.2, 12.3, 3.7 Hz), 144.2 (q, JCF = 38.8 Hz), 124.6 (ddd , JCF = 18.5, 5.9, 4.0 Hz), 120.4 (dd , JCF = 19.1, 6.2 Hz), 119.8 (q, JCF = 268.9 Hz), 106.2 (dd , JCF = 29.5,20.9 Hz), 50.1, 44.8, 44.3 (minor), 43.2 (minor), 42.4, 41.6 (minor), 41.4, 39.6, 38.5 (minor), 36.9.; The following high-performance liquid chromatographic (HPLC) conditions were used to determine percent conversion to product: Column: Waters Symmetry C18, 250 mm x 4.6 mm Eluent: Solvent A: 0.1 vol percent HC104/H20 Solvent B: acetonitrile Gradient: 0 min 75percent A : 25percent B 10 min 25percent A : 75percent B 12.5 min 25percent A: 75percent B 15 min 75percent A : 25percent B Flow rate: 1 mL/min Injection Vol. : 10 muL UV detection: 210 nm Column temp.: 40 ¡ãC Retention times: compound 2-4: 9.1 min compound 2-5: 5.4 min The following high-performance liquid chromatographic (HPLC) conditions were used to determine optical purity: Column: Chirapak, AD-H, 250 mm x 4.6 mm Eluent: Solvent A: 0.2 vol.percent diethylamine in heptane Solvent B: 0.1 vol percent diethylamine in ethanol Isochratic Run Time: 18 min Flow rate: 0.7 mL/min Injection Vol.: 7 muL UV detection: 268 nm Column temp.: 35 ¡ãC Retention times: (R) -amine 2-5: 13.8 min (S)-amine: 11.2 min

Statistics shows that (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine is playing an increasingly important role. we look forward to future research findings about 767340-03-4.

Reference:
Patent; MERCK & CO., INC.; SOLVIAS AG; WO2005/97733; (2005); 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 5424-01-1 as follows. 5424-01-1

General procedure: Used for N-benzyl derivatives 1-8. The starting 3-aminopyrazine-2-carboxylic acid(Sigma-Aldrich, Schnelldorf, Germany; 2.2 g; 15.8 mmol) in methanol (250 mL) was cooled downto 0 C and concentrated H2SO4 (3.2 mL) was added. The reaction mixture was stirred for 48 h atrt. Subsequently the reaction mixture was poured into water (27 mL) and alkalized by NaHCO3(approx. 6.3 g) to pH = 7. The precipitate was filtered off and collected as white-brown solid toobtain methyl 3-aminopryzine-2-carboxylate [32]. Methyl 3-aminopyrazine-2-carboxylate (100 mg;0.65 mmol) in methanol (2 mL) along with substituted benzylamine (1.95 mmol; 3 equiv) and NH4Cl(10 mg; 0.19 mmol; 0.1 equiv) [33] were put into reaction tube used for microwave assisted synthesiswith a magnetic stirrer. Reaction was performed in a CEM Discover microwave reactor with a focusedfield in pressurized vials with the following settings: 130 C, 90 W and 40 min. The progress of thereaction was checked using TLC (Merck Silica 60 F254) developed by in hexane/ethyl-acetate 2:1 system.The reaction mixture was adsorbed to silica gel and purified by flash chromatography (Teledyne IscoInc.,) using silica (irregular, 40-63 m) as a stationary phase and gradient elution EtOAc in hexane0-100%, with respect to the expected lipophilicity of the product.

According to the analysis of related databases, 5424-01-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Bouz, Ghada; Semelkova, Lucia; Jand?ourek, Ond?ej; Kone?na, Klara; Paterova, Pavla; Navratilova, Lucie; Kubi?ek, Vladimir; Kune?, Ji?i; Dole?al, Martin; Zitko, Jan; Molecules; vol. 24; 7; (2019);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding some certain compound to certain chemical reactions, such as: 63744-22-9, name is 6,8-Dibromoimidazo[1,2-a]pyrazine, 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 63744-22-9. 63744-22-9

Intermediate Example 2-1 :Preparation of 6-bromo-8-methylsulfan l-imidazo[1 ,2-a]pyrazineTo a stirred suspension of intermediate example 1 -16,8-dibromo-imidazo[1 ,2-a]pyrazine (489 g, 1766 mmol) in MeOH (2900 mL) at -20 C was dropwise added a solution of sodium methan thiolate (225 g, 3214 mmol, 1 .8 eq) in 800 mL water. After stirring overnight, the clear solution was poured on 30 L water and the yellowish precipitate was filtered, washed with 3 L water and dried in vaccuo to yield 301 g 6-bromo-8-methylsulfanyl-imidazo[1 ,2-a]pyrazine (69.8 %). 1 H-NMR (300 MHz, d6-DMSO): delta = 8.64 (1 H, s), 8.00 (1 H, d), 7.66 (1 H, d2.54 (3H, s) 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 6,8-Dibromoimidazo[1,2-a]pyrazine.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; KOPPITZ, Marcus; KLAR, Ulrich; JAUTELAT, Rolf; KOSEMUND, Dirk; BOHLMANN, Rolf; BADER, Benjamin; LIENAU, Philip; SIEMEISTER, Gerhard; WO2012/80228; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem