Category: Pyrazines

Adding a certain compound to certain chemical reactions, such as: 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, 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 16298-03-6, Formula: C6H7N3O2

(A) Methyl 2-bromo-3-pyrazine carboxylate: To a stirred mixture of 12.7 g. of methyl 2-aminopyrazine 3-carboxylate and 47 ml. of 48% hydrobromic acid there is added, dropwise, 12.6 ml. of bromine keeping the temperature at 0. A solution of 14.4 g. of sodium nitrite in 60 ml. of water is then added, dropwise, at 0 and the reaction mixture stirred for 15 minutes. The reaction mixture is basified to pH 8 with sodium bicarbonate and extracted with ethyl acetate and again with chloroform. The organic layers are dried over magnesium sulfate, filtered and concentrated to a yellow oil. Recrystallization from ether-hexane yields the product, m.p. 43-45 C.

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

Reference:
Patent; Schering Corporation; US4551463; (1985); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, 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 5521-55-1, Formula: C6H6N2O2

To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added 5-methylpyrazine-2-carboxylic acid (1.0 eq), toluene (2.5 vols) and di-isopropylethylamine (1.50 eq) under a nitrogen atmosphere. The mixture was vacuum distilled at a batch temperature of 50 C., distilling to a final volume of 2 vols. The batch was sampled to ensure the water content was <0.1% w/w, then cooled to 15+-2 C., and diphenylphosphorylazide (1.00 eq) was added over a time period of 5-6 hours, maintaining the temperature of the reaction mixture at 15+-2 C. The mixture was stirred for a further 1.5 hours. Meanwhile to a second flask was added benzyl alcohol (3.00 eq) and toluene (11 vols). The mixture was azeotropically dried to a volume of 10 vols. The contents of the second flask were sampled to ensure the water content was <0.1% w/w, then heated to 85-90 C. The contents of the first flask were added slowly to the contents of the second flask over approximately 2 hours, maintaining the reaction temperature at approximately 85 C. The reaction mixture was stirred for 1 hour at 85 C., then cooled to 20 C. 5% w/w Sodium hydroxide solution (1.75 eq) was added slowly over 1 hour, the mixture cooled to 5 C., agitated at 5 C. for 1 hour, then filtered. The isolated solid was washed sequentially with water (2 vols), then methanol (2 vols). After drying in the vacuum oven at 40 C. overnight, the desired product was obtained as a solid (corrected yield 78-85%). 1H NMR (400 MHz, CDCl3): 9.41 bs (1H), 9.24 s (1H), 7.87 s (1H), 7.39-7.41 m (5H), 5.22 s (2H), 2.31 s (3H) 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-Methylpyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see. Reference:
Patent; AstraZeneca AB; US2010/210841; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 32587-10-3, 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 32587-10-3 as follows.

EXAMPLE 3 Synthesis of 3-Aminopyrazine-2-carbonitrile (Intermediate 2) To a solution of intermediate 1 (3.5 g, 25 mmol) in DMF (40 mL) at RT was added POCl3 (4.5 mL, 49 mmol) slowly. The resulting mixture was heated at 80 C. for 15 min and then cooled to RT. The mixture was poured into ice water and the mixture neutralized with 10% NaOH solution. The resulting solid was filtered and redissolved in 5% HCl. The solution was heated at 70 C. for 30 min and the resulting solid filtered. After thoroughly washed with water, the title compound was obtained as a brown solid (1.7 g, 56%). 1H NMR (500 MHz, DMSO-d6): delta 8.28 (d, J=2.4 Hz, 1H), 7.90 (d, J=2.4 Hz, 1H), 7.32 (br s, 2H). MS (ES+): m/z 121 (M+H)+.

According to the analysis of related databases, 32587-10-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; TargeGen, Inc.; US2007/259876; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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

Methyl 4-iodobenzoate (2.84 g, 10.86 mmol), cesium carbonate (7.07 g, 21.71 mmol), 2-acetylcyclohexanone (0.286 mL, 2.17 mmol) and copper(I) iodide (0.103 g, 0.54 mmol) were added to a stirred solution of 2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine (1.5224 g, 10.86 mmol) in DMF (30 mL) under nitrogen. The resulting suspension was stirred at 90 C. for 20 h. The reaction mixture was evaporated to dryness and dissolved in methanol. The crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 3.5M NH3/MeOH and pure fractions were evaporated to dryness to afford a brown gum. This was purified again by silica column chromatography, eluting with 5% MeOH (containing 0.1% ammonium hydroxide) in DCM. Pure fractions were evaporated to dryness to afford the desired compound (0.503 g, 16.8%) as an orange solid 1H NMR (399.9 MHz, CDCl3) delta 1.29-1.33 (1H, m), 1.26-1.40 (1H, m), 1.62 (1H, d), 1.64 (1H, d), 1.65-1.68 (1H, m), 1.69 (1H, s), 1.80-1.82 (1H, m), 2.04-2.10 (2H, m), 2.32-2.39 (1H, m), 2.61 (1H, d), 2.89 (2H, d), 3.01-3.08 (1H, m), 3.58-3.63 (1H, m), 3.70-3.75 (1H, m), 3.86 (3H, s), 6.83-6.87 (2H, m), 7.89-7.93 (2H, m). MS m/z=275 (MH+).; Methyl -4-iodobenzoate (2.84 g, 10.86 mmol), cesium carbonate (7.07 g, 21.71 mmol), 2-acetylcyclohexanone (0.286 mL, 2.17 mmol) and copper(I) iodide (0.103 g, 0.54 mmol) were added to a stirred solution of 2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine (1.5224 g, 10.86 mmol) in DMF (30 mL) under nitrogen. The resulting suspension was stirred at 90 C. for 20 h. The reaction mixture was evaporated to dryness. The crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 3.5M NH3/MeOH and fractions were evaporated to dryness to afford the crude product as an impure brown gum. The crude product was purified by silica column chromatography, eluting with 5% MeOH, 0.1% aqueous ammonia in DCM. Pure fractions were evaporated to dryness to afford the desired compound (0.681 g, 22.87%) as an orange solid. 1H NMR (399.9 MHz, CDCl3) delta 1.29-1.33 (1H, m), 1.26-1.40 (1H, m), 1.62 (1H, d), 1.64 (1H, d), 1.65-1.68 (1H, m), 1.69 (1H, s), 1.80-1.82 (1H, m), 2.04-2.10 (2H, m), 2.32-2.39 (1H, m), 2.61 (1H, d), 2.89 (2H, d), 3.01-3.08 (1H, m), 3.58-3.63 (1H, m), 3.70-3.75 (1H, m), 3.86 (3H, s), 6.83-6.87 (2H, m), 7.89-7.93 (2H, m). MS: m/z 275 (MH+).

The synthetic route of 4430-75-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; US2008/153812; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 33332-29-5, 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. 33332-29-5, name is 2-Amino-5-chloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

General procedure: Method B is a modification of Method A and was performed under nitrogen atmosphere andwith extended work-up. Substituted benzoyl chloride (1.5 mmol, 1.2 equiv) was placed into the askunder nitrogen, diluted with dry DCM (5 mL) and dry pyridine (400 mg, 5 mmol, 4 equiv) was added.The mixture was mixed for 5 min under nitrogen. Then, 5-chloropyrazin-2-amine (162 mg, 1.25 mmol,1 equiv) dissolved in DCM (10 mL) was added dropwise over 10 min under nitrogen ow. The askwas closed by septum and stirred for additional 6 h. After reaction, the mixture was diluted with DCMto the final volume of 40 mL and washed with water (1 30 mL), 5% (m/m) aqueous NaHCO3 solution(1 30 mL), and brine (1 30 mL). The organic layer was dried over anhydrous Na2SO4 and adsorbedon silica (4 g) by evaporating the solvents under reduced pressure. Automated flash chromatographywas run using same conditions as described in Method A. If needed, the products were recrystallizedfrom hot EtOH (crystallization initiated by cooling and dropwise addition of cold water).

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-Amino-5-chloropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Zitko, Jan; Mindlova, Al?b?ta; Vala?ek, Ond?ej; Jand’ourek, Ond?ej; Paterova, Pavla; Janou?ek, Ji?i; Kone?na, Klara; Dole?al, Martin; Molecules; vol. 23; 9; (2018);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 32111-21-0,Some common heterocyclic compound, 32111-21-0, name is 2-Iodopyrazine, molecular formula is C4H3IN2, 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 9 A flask was charged with pinacol borobate (383.0 mg, 1.0 mmol), iodopyrazole (226.6 mg, 1.1 mmol), Pd(OAc)2 (11.2 mg, 0.05 mmol), TFP (46.4 mg, 0.2 mmol), K2CO3 (690.0 mg, 5 mmol), water (3 mL) and DME (2 mL). After 3 vacuum/argon cycles, the resulting mixture was heated to 80 C. 45 min later, HPLC revealed that all boronate disappeared. The area ratio of C-H, coupling product and dimer was about 3.3:85.3:11.4 on HPLC. After the reaction mixture was cooled down to room temperature, EtOAc (5 mL) was added. The aqueous layer was separated and extracted with EtOAc (2*10 mL). The combined organic extracts were washed with brine (10 mL), dried over Na2SO4, and concentrated in vacuo. The crude product was purified via silica gel chromatography to afford the indole (0.27 g, 81%). 1H NMR (300 HMz, CDCl3) delta 8.77 (2H, bs), 8.60 (1H, s), 8.16 (1H, s), 7.82-7.76 (2H, m), 3.96 (3H, s), 3.78 (3H, s), 3.20 (1H, m), 2.08-1.92 (6H, m), 1.72-1.69 (2H, m); 13C NMR (100 HMz, CDCl3) delta 168.0, 147.4, 146.6, 144.4, 143.2, 138.0, 135.3, 129.0, 124.2, 120.5, 120.3, 120.0, 112.4, 52.0, 37.3, 33.6, 31.3, 26.5.

The synthetic route of 32111-21-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Boehringer Ingelheim International GmbH; US2006/183752; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 5049-61-6, name is Pyrazin-2-amine, 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 Pyrazin-2-amine

To a mixture of 2-amino pyrazine (50 g, 0.5 mol) in chloroform (1000 ml) cooled to 0C was added pyridine (100 ml, 1.21 mol) and bromine (54 ml, 1.05 mmol) dropwise. The mixture was stirred at rt for 16h, then water was added. The organic phase was extracted, dried (MgS04), filtered and evaporated to obtain I- 01 , 48 g (Y: 36 %) of a yellow solid which was dried in vacuo.

The synthetic route of Pyrazin-2-amine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CENTRO NACIONAL DE INVESTIGACIONES ONC&Oacgr;LOGICAS (CNIO); PASTOR FERNANDEZ, Joaquin; MARTINEZ GONZALEZ, Sonia; ALVAREZ ESCOBAR, Rosa Maria; RODRIGUEZ ARISTEGUI, Sonsoles; GONZALES CANTALAPIEDRA, Esther; HERNANDEZ HIGUERAS, Ana Isabel; VARELA BUSTO, Carmen; WO2011/36461; (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. 313339-92-3, name is 3,5-Dichloropyrazine-2-carbonitrile belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 3,5-Dichloropyrazine-2-carbonitrile

3,5-Dichloropyrazine-2-carbonitrile (202 mg, 1.16 mmol), (racemic)-cis-tert-butyl octahydro- 1H-pyrrolo[3,2-b]pyridine-1-carboxylate (250 mg, 1.105 mmol) and DIEA (0.770 mL, 4.42 mmol) were dissolved in EtOH (10 mL) and stirred at 40 C for 45 minutes. The reaction mixture was diluted with ethyl acetate and washed with aqueous solution of NaHCO3 and with water. The organic phase was dried over filtered and concentrated under high vacuum to give tert-butyl-4-(6-chloro-5-cyanopyrazin-2-yl)-octahydro-1H-pyrrolo[3,2-b]pyridine-1- carboxylate (477 mg, quant. yield) as racemic-cis mixture. MS found for C17H22ClN5O2 as (M+H)+ 364.2.

The synthetic route of 313339-92-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PHARMACYCLICS LLC.; ATALLAH, Gordana, Babic; CHEN, Wei; JIA, Zhaozhong, J.; POZZAN, Alfonso; RAVEGLIA, Lucal, Francesco; ZANALETTI, Riccardo; (815 pag.)WO2016/196776; (2016); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 76537-18-3, These common heterocyclic compound, 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, 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. 5-Chloro-3-(2-methylprop-1-en-1-yl)pyrazin-2-amine, 37a (0433) (0434) A mixture of 3-bromo-5-chloropyrazin-2-amine (41 g, 0.20 mol), 4,4,5,5-tetramethyl-2-(2-methylprop-1-en-1-yl)-1,3,2-dioxaborolane (34 g, 0.19 mol), Pd(dppf)Cl2 (3.0 g, 4.1 mmol), K2CO3 (85 g, 0.62 mol,) in dioxane (600 mL) and water (100 mL) was stirred for 24 h at 80 C. under N2. The reaction was allowed to cool to RT and then quenched by the addition of 1 L of water/ice. The resulting solution was extracted with EtOAc (2¡Á2 L). The organic layers were combined, dried (Na2SO4) and concentrated. The resulting black oil was used in the next step without further purification. Mass Spectrum (LCMS, ESI pos.): Calcd. for C8H10ClN3: 184.1 (M+H)+; found: 184.1.

Statistics shows that 3-Bromo-5-chloropyrazin-2-amine is playing an increasingly important role. we look forward to future research findings about 76537-18-3.

Reference:
Patent; Janssen Pharmaceutica NV; Meegalla, Sanath; Huang, Hui; Player, Mark R.; (53 pag.)US2016/9662; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 193966-70-0, These common heterocyclic compound, 193966-70-0, name is Methyl 5-(bromomethyl)pyrazine-2-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.

To a suspension of compound 3 in trifluoroacetic acid (TFA, CAS Reg. No. 866268-31-7, prepared according to WO 2011/049815 A1, 1.824 g, 5.19 mmol)nd cesium carbonate (5.42 g, 16.62 mmol) in DMF (20 mL) was added compound 2 (1.2 g, 5.19 mmol). The reaction mixture was stirred at RT for 1 h, after which the reaction was complete. After quenching with water, the resulting solid was collected by filtration and rinsed with water and air dried in vacuo to yield compound 4 (1.67 g, 4.31 mmol, 83% yield) which was carried over to next step without further purification. LCMS ESI: calculated for C17H21H7O4=388.2 (M+H+), found 388.1 (M+H+). 1H NMR (400 MHz, CHLOROFORM-d) delta 9.20 (d, J=1.3 Hz, 1H), 8.68 (s, 1H), 5.36 (s, 2H), 4.33-4.27 (m, 2H), 4.11 (s, 3H), 4.04 (s, 2H), 1.77-1.70 (m, 2H), 1.46 (br d, J=7.7 Hz, 2H), 0.93 (t, J=7.5 Hz, 3H).

Statistics shows that Methyl 5-(bromomethyl)pyrazine-2-carboxylate is playing an increasingly important role. we look forward to future research findings about 193966-70-0.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; POUDEL, Yam B.; He, Liqi; Gangwar, Sanjeev; Posy, Shoshana L.; Sivaprakasam, Prasanna; (38 pag.)US2019/55245; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem