Month: March 2021

Adding a certain compound to certain chemical reactions, such as: 622392-04-5, name is 2-Bromo-5-iodopyrazine, 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 622392-04-5, category: Pyrazines

Add 30 g of 2-bromo-5-iodopyrazine, 300 ml of toluene to a 500 ml three-necked flask.Displace nitrogen protection and then add 26.7 ml of hexa-butyltin di-tin.After the reaction solution was stirred at room temperature for 3 hours,0.61 g of tetrakis(triphenylphosphine)palladium was added, and the mixture was heated to 120 C and stirred for 8 hours.The TLC monitors the complete reaction of the starting material to stop the reaction.After the reaction solution is cooled to room temperature, the column removes insoluble impurities.The crude product obtained after concentration of the eluent was recrystallized from toluene to yield 12.6 g of white solid.The yield was 76.2%.

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

Reference:
Patent; Xi’an Ruilian New Materials Co., Ltd.; Zhang Hongke; Sun Jun; Liu Kaipeng; Wang Xiaowei; Liu Qianfeng; Gao Renxiao; Cai Liang; Yang Yan; (34 pag.)CN109053696; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 109-08-0, 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 109-08-0 as follows.

EXAMPLE 21; 3-(3,4-Dimethyl-lH-indol-l-yl)-N’-(3-methoxy-4-(pyrazin-2- ylmethoxy)benzylidene)propanehydrazide; [0533] (a) 2-(Chloromethyl)pyrazine: A solution of 2-methylpyrazine (0.75 mL, 8.0 mmol), NCS (1.5 g, 11.4 mmol) and benzoyl peroxide (96 mg, 0.4 mmol) in CCl4 (30 mL) was refluxed overnight. After cooling to room temperature, the reaction was diluted with EtOAc, washed with water, brine and dried (Na2SO4). The crude material obtained (-600 mg) was used directly in the next step

According to the analysis of related databases, 109-08-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; STEIN, Philip; DAINES, Robert; SPROUS, Dennis; O’GRADY, Harold; WO2010/132615; (2010); 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. 59303-10-5, name is 2-Chloro-5-methylpyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. SDS of cas: 59303-10-5

A microwave vial was charged with tert-butyl 4-((2S ,3R,4R)- I -acetyl-4-amino-2,3-dimethyl- 1,2,3,4-tetrahydroquinolin-6-yl)piperazine- I -carboxylate (for a preparation see Intermediate 213, 69 mg,0.151 mmol) in 1,4-dioxane (2 mL) followed by 2-chloro-5-methylpyrazine (37 mg, 0.288 mmol),then sodium tert-butoxide (27 mg, 0.281 mmol), DavePhos (12 mg, 0.030 mmol), and Pd2(dba)3 (26 mg, 0.028 mmol). The reaction mixture was heated to 100 C for 45 mm using a microwave reactor, then diluted with EtOAc and filtered through a pad of celite. The celite pad was washed with EtOAc (10 mL) and the filtrate concentrated under reduced pressure. The residue was purified by MDAP(Formic). The desired fractions were combined and evaporated in vacuo to afford the desired product

The synthetic route of 59303-10-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; AMANS, Dominique; ATKINSON, Stephen John; HARRISON, Lee Andrew; HIRST, David Jonathan; LAW, Robert Peter; LINDON, Matthew; PRESTON, Alexander; SEAL, Jonathan Thomas; WELLAWAY, Christopher Roland; WO2014/140076; (2014); A1;,
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. 41110-29-6, name is Methyl 3-methylpyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., SDS of cas: 41110-29-6

A solution of methyl 3-methylpyrazine-2-carboxylate (9.1 g, 59.8 mmol) in DCM (100 mL) was cooled to 0 C. was added urea hydrogen peroxide adduct (7.8 g, 83.0 mmol), followed by dropwise addition of trifluoroacetic acid anhydride (10.8 mL, 78.0 mmol). The resulting mixture was stirred at 0 C. for 1 h, and at RT for 18 h, during which LCMS indicated a mixture of two peaks corresponding to MS m/z=169.0 [M+H]+. The reaction was diluted with DCM and quenched with saturated Na2SO3 solution; the aqueous layer was back-extracted with DCM (2¡Á). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. ISCO purification (20-80% EtOAc/hexanes) afforded a mixture of two regioisomers, containing 3-(methoxycarbonyl)-2-methylpyrazine 1-oxide and 2-(methoxycarbonyl)-3-methylpyrazine 1-oxide (5.2 g, 30.9 mmol, 51.7% yield). The mixture of regioisomers was taken to next step without further purification. MS m/z=169.0 [M+H]+. A solution of the mixture of 3-(methoxycarbonyl)-2-methylpyrazine 1-oxide and 2-(methoxycarbonyl)-3-methylpyrazine 1-oxide (5.1 g, 15.2 mmol) in toluene (50 mL) was cooled to 0 C. and phosphorus oxychloride (2.8 mL, 30.3 mmol) was added under nitrogen followed by DMF (0.12 mL, 1.52 mmol). The reaction mixture was stirred at RT for 4 h, and heated to 65 C. for 18 h, cooled to RT, diluted with EtOAc and washed with saturated NaHCO3 solution. The aqueous layer was back-extracted with EtOAc (2¡Á). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. ISCO purification (0-50% EtOAc/hexanes) with care afforded both isomers: methyl 5-chloro-3-methylpyrazine-2-carboxylate (0.68 g) (minor product) denoted by peak 1 and methyl 6-chloro-3-methylpyrazine-2-carboxylate (1.50 g) (major product) denoted by peak 2. MS m/z=187.0 [M+H]+. Peak 1: 1H NMR (300 MHz, DMSO-d6) delta 8.73 (s, 1H), 3.91 (s, 3H), 2.71 (s, 3H). Peak 2: 1H NMR (300 MHz, DMSO-d6) delta 8.89 (s, 1H), 3.91 (s, 3H), 2.71 (s, 3H).

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; LEWIS, Richard T.; ALLEN, Jennifer R.; BROWN, James; GUZMAN-PEREZ, Angel; HUA, Zihao; JUDD, Ted; LIU, Qingyian; OLIVIERI, Philip R.; ROMERO, Karina; SCHENKEL, Laurie; STELLWAGEN, John; WHITE, Ryan; US2015/38497; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 33332-28-4, A common heterocyclic compound, 33332-28-4, name is 2-Amino-6-chloropyrazine, molecular formula is C4H4ClN3, 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.

EXAMPLE 9 N-(6-Chloro-pyrazin-2-yl)-4-hydroxy-2-n-propyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide 2.97 g (10 mmols) of methyl 2-n-propyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide and 1.3 g (10 mmols) of 2-amino-6-chloro-pyrazine were reacted in 150 ml of xylene analogous to Example 1, yielding 2.05 g (52percent of theory) of N-(6-chloro-pyrazin-2-yl)-4-hydroxy-2-n-propyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide. C16 H15 ClN4 O4 S (394.86): Calc.: C–48.67percent; H–3.83percent; Cl–8.98percent; N–14.19percent; S–8.12percent. Found: C–48.91percent; H–3.79percent; Cl–8.90percent; N–14.18percent; S–8.03percent.

The synthetic route of 33332-28-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Dr. Karl Thomae Gesellschaft mit beschrankter Haftung; US4533664; (1985); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 41270-66-0, 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. 41270-66-0, name is 5-Chloro-2,3-diphenylpyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To the stirred mixture of 5-chloro 2-3 diphenyl pyrazine (100 g, 0.375 mol) & 4-lsopropylamino-butyric acid ethyl ester (257.97 g, 1.49 mol) was added at room temperature. Reaction mixture was stirred at 185-190C temperature for 24 hr. Reaction was monitored by HPLC analysis. After completion of reaction, charged purified Water and product extracted in Ethyl acetate, which was washed using 5% sodium bicarbonate to remove the hydroxyl impuritiy produced during the reaction. Then the ethyl acetate layer was concentrated to obtain the 4-[(5,6-diphenyl-pyrazin-2-yl)-isopropyl-amino]- butyric acid ethyl ester. [Yield = 90 g; Purity (HPLC) = 88.71 %]

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-Chloro-2,3-diphenylpyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MEGAFINE PHARMA (P) LTD.; MATHAD VIJAYAVITTHAL THIPPANNACHAR; DODDAPPA PRALHAD ANEKAL; KARDILE PRITESH BHIMRAJ; PADAKI SANTHOSH AMBADAS; GAIKWAD BAPUSAHEB SHRIHARI; SHINDE GORAKSHANATH BALASAHEB; (63 pag.)WO2017/42828; (2017); A2;,
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. Application In Synthesis of Methyl 2-pyrazinecarboxylate

Procedure: ¡¤ Charged ST-601 (1 kg), NaH, 60 wt.% (579 g) and toluene (10 vol) and stirred at 15/25 C. No reaction (no gas evolution, exotherm or appearance change). (0157) ? Charged methyl propionate (64 g). No immediate reaction (no gas evolution, exotherm or appearance change) at 15/25 C. ? Charged MeOH (85 g) at 15/25 C. Immediately started to react (gas evolution, exotherm). Heated to 30/40 C. (0158) ? Charged methyl propionate (893 g) at 30/40 C over 5 h. The reaction was slower in the beginning, but became faster (more exotherm and gas evolution) after 1-2 h when -0.3 eq of methyl propionate was charged. Stirred at 30/40 C for 88 h. (0159) 64 h, 30/35 C, brown slurry, practically no gas evolution observed, IPC HPLCl: 74.4% + 14.1 % = 88.5% o/ ST-602 at 4.81 min and 5.62 min; 1.2% of ST -601 at 1.97 min; 5.8% of “Int” at 3.21 min. (0160) 72 h, 35 C, IPC HPLC2: 47.8% + 42.9%c=90 % o/ST-602; 0.9% ofST-601; 4.3% of “Int” 88 h, 38 C, IPC HPLC3: 60.3% + 32.6%=92.9% o/ST-602; 0.64% ofST-601; 1.8% of “Int” (0161) ? Reaction was cooled to 15/20 C. (0162) ? Charged AcOH (2.5 eq) over a minimum of 1 hr. Exothermic. Slightly thick, brown suspension. (0163) ? Charged 10% NaCl solution (8 vol) over a minimum of 1 h at 15/30 C. Slight exotherm. Brown, biphasic solution. Let stir at 15/30 C for a minimum of 30 min to dissolve all solids. (0164) ? The phases were separated. Both the aqueous and the organic phases were brown. (0165) ? The organic phase was washed with a 10% NaCl solution (5 vol). (0166) ? The organic phase was washed with NaHC03 (0.1 g/g SM) in 10% aq. NaCl solution (5 vol.) (0167) ? The organic phase was dried over anhydrous sodium sulfate (0.2 g/g SM) for a minimum of 2 hrs. (0168) ? Solids were filtered off and rinsed with Toluene (l x l vol) (0169) ? Concentrated to 3-4 vol at (0170) Isolated material: ST- 602 (0171) Lot No.: 2463-52-2 (0172) Appearance: light brown liquid (0173) Yield: Assumed 100% (1406 g net directly used in next step) HPLC: 94.3% of ST-602

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

Reference:
Patent; ST IP HOLDING AG; FRAMROZE, Bomi P.; (65 pag.)WO2016/207914; (2016); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 1379338-74-5, name is 5,7-Dichloropyrido[3,4-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. HPLC of Formula: C7H3Cl2N3

Intermediate 18: 1,1-Dimethylethyl (3S)-3-{[(7-chloropyrido[3,4-b]pyrazin-5-yl)oxy]methyl}-1-piperidinecarboxylate 1,1-Dimethylethyl (3S)-3-(hydroxymethyl)-1-piperidinecarboxylate (129 mg, 0.600 mmol) (Apollo Scientific Limited) was taken up in N,N-dimethylformamide (DMF) (3 ml), treated with sodium hydride (23.99 mg, 0.600 mmol) and allowed to stir at room temperature for 20 min, a yellow solution resulted. 5,7-dichloropyrido[3,4-b]pyrazine (100 mg, 0.500 mmol) was added and the reaction was allowed to stir at room temperature for a further 1 h. The reaction was partitioned between EtOAc (50 ml) and NH4Cl (50 ml). The organic layer was dried using a hydrophobic frit and concentrated to give a brown oil. This oil was purified on silica (25 g) using a 0-40% EtOAc/cyclohexane gradient. The appropriate fractions were summed and concentrated to give the title compound as a yellow gum (91 mg). LCMS (Method B): Rt=1.26 min, MH+=378.88

The synthetic route of 5,7-Dichloropyrido[3,4-b]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; Atkinson, Francis Louis; Atkinson, Stephen John; Barker, Michael David; Douault, Clement; Garton, Neil Stuart; Liddle, John; Patel, Vipulkumar Kantibhai; Preston, Alexander G.; Shipley, Tracy Jane; Wilson, David Matthew; Watson, Robert J.; US2014/5188; (2014); 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., Quality Control of 2,5-Dichloropyrazine

Step C: A flask was charged with (S)-3-(lH-indazol-5-yloxy)-l-(piperidin-4- yl)pyrrolidin-2-one (0.120 g, 0.400 mmol), 2,5-dichloropyrazine (0.0655 g, 0.439 mmol), DIEA (d 0.742) (0.0696 mL, 0.400 mmol), and DMF (3 mL). The reaction was stirred at 100 ¡ãC overnight. The organic solvents were removed under reduced pressure. The residue was purified using preparative TLC with 10percent methanol in ethyl acetate to provide (S)-3-(lH- indazol-5-yloxy)-l-(l-(5-chloropyrazin-2-yl)piperidin-4-yl)pyrrolidin-2-one (0.0047 g, 0.0114 mmol, 2.85percent yield). Mass spectrum (apci) m/z = 413.2 (M+H).

According to the analysis of related databases, 19745-07-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ARRAY BIOPHARMA INC.; AICHER, Thomas Daniel; BENCSIK, Josef Roland; BOYD, Steven Armen; CONDROSKI, Kevin Ronald; FELL, Jay Bradford; FISCHER, John P.; HINKLIN, Ronald Jay; PRATT, Scott Alan; SINGH, Ajay; TURNER, Timothy M.; WO2011/146335; (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. 74290-67-8, name is 2-Amino-5-bromo-3-methylpyrazine, This compound has unique chemical properties. The synthetic route is as follows., category: Pyrazines

Example 110 N-(3-((5-amino-6-methylpyrazin-2-yl)ethynyl)-2,4-difluorophenyl)-5-chloro-2-methoxypyridine-3-sulfonamide A mixture of 5-chloro-N-(3-ethynyl-2,4-difluorophenyl)-2-methoxypyridine-3-sulfonamide (108 mg), 2-amino-5-bromo-3-methylpyrazine (54 mg), dichlorobis(tricyclohexylphosphine)palladium(II) (11 mg), cesium carbonate (290 mg) and DMSO (2 mL) was stirred under microwave irradiation at 120 C. for 2 hr. After cooling to room temperature, the reaction mixture was purified by silica gel column chromatography (ethyl acetate/hexane) and further purified by HPLC (C18, mobile phase: water/acetonitrile (0.1% TFA-containing system)). Fractions containing the object product were collected, neutralized with a saturated aqueous sodium hydrogen carbonate solution and extracted 2 times with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was washed with ethyl acetate/IPE and dried under reduced pressure to give the title compound (63 mg). 1H NMR (300 MHz, DMSO-d6) delta 2.30 (3H, s), 3.93 (3H, s), 6.86 (2H, s), 7.10-7.23 (1H, m), 7.32 (1H, td, J=8.9, 6.0 Hz), 8.04 (1H, s), 8.06 (1H, d, J=2.5 Hz), 8.49 (1H, d, J=2.6 Hz), 10.46 (1H, s).

According to the analysis of related databases, 74290-67-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Takeda Pharmaceutical Company Limited; FUJIMOTO, Jun; LIU, Xin; KURASAWA, Osamu; TAKAGI, Terufumi; CARY, Douglas Robert; BANNO, Hiroshi; ASANO, Yasutomi; KOJIMA, Takuto; (159 pag.)US2019/169166; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem