Month: July 2021

Reference of 6966-01-4,Some common heterocyclic compound, 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, molecular formula is C6H6BrN3O2, 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 2: 3-Amino-6-bromopyrazine-2-carboxylic acid[00140] A mixture of methyl 3-amino-6-bromo-pyrazine-2-carboxylate (5.1 1 g, 22.02 mmol) and lithium hydroxide (2.637 g, 110.1 mmol) in MeOH (20 mL) and Iota¾0 (20 mL) was heated to 90 C for 2 hours. The reaction mixture was allowed to cool and neutralized with HCl and the resultant precipitate collected by filtration. The sub-title product was taken on to the next step without further purification (4.80g, 99% Yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-amino-6-bromopyrazine-2-carboxylate, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-Damien; DURRANT, Steven, John; KNEGTEL, Ronald, Marcellus, Alphonsus; O’DONNELL, Michael; REAPER, Philip, Michael; WO2011/143419; (2011); 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. 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, A new synthetic method of this compound is introduced below., SDS of cas: 16298-03-6

To a solution of methyl 3-amino- pyrazine-2- carboxylate (5.00 g, 32.7 mmol) in 1,2-dimethoxyethane (80 mL) were added ?2 (4.14 g, 16.3 mmol), copper(I) iodide (1.87 g, 9.80 mmol) and cesium iodide (8.48 g, 32.7 mmol) undernitrogen. Then isoamyl nitrite (13.2 mL, 98.0 mmol) was added dropwise at 20 C. The reaction was stirred at 75 C for 2 h, then quenched with water (100 mL). The aqueous layer was extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (30 mL), dried over anhydrous MgSO4 and filtered. The filtrate was concentrated in vacuo to give a residue, which was purified by silica gel chromagraphy eluting withPE/EtOAc (5i02, PE: EtOAc = 1: O1O:1, v/v) to give the title compound. MS (ESI) mlz:264.7 [M+Hj ?H NMR (400MHz, DMSO-d6) oe = 8.71 (d, J=2.2 Hz, 1H), 8.63 (d, J2.0Hz, 1H), 3.93 (s, 3H)

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

Reference:
Patent; MERCK SHARP & DOHME CORP.; MILLER, Michael; CHOBANIAN, Harry, R.; HE, Shuwen; HAO, Jinsong; PIO, Barbara; GUO, Yan; XIAO, Dong; (213 pag.)WO2018/118670; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 5780-66-5, A common heterocyclic compound, 5780-66-5, name is Pyrazine-2-carbaldehyde, molecular formula is C5H4N2O, 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 5 Synthesis of the compound represented by the following formula; [Show Image] The compound A (50 mg) and 2-pyrazinecarboxyaldehyde (200 mg) were dissolved in methanol (10 ml) and then 100 mul of acetic acid was added thereto, followed by stirring at 80°C for 3 hours. After the reaction solution was neutralized with triethylamine, it was filled on a Sephadex LH-20 column chromatography and developed with methanol. The desired fraction was concentrated and dried to give a hydrazone compound (45 mg). The resulting hydrazone compound (20 mg) was dissolved in methanol-tetrahydrofuran (1:1) (10 ml) and then NaBH3CN (20 mg) and 10percent HCl-MeOH (3 ml) were added thereto, followed by stirring for 60 minutes. After the reaction solution was concentrated, a small amount of triethylamine was added to the residue and the mixture was filled on a Sephadex LH-20 column chromatography and developed with methanol. The desired fraction was concentrated and dried to give the compound represented by the above formula (6.0 mg) as a red solid. FAB (m/z): 627 (M + H)+ 1H-NMR (300 MHz, DMSO-d6, delta ppm): 11.23 (1H, s), 9.03 (1H, d, J = 1.2 Hz), 8.82 (1H, d, J = 8.7 Hz), 8.74 (1H, d, J = 8.4 Hz), 8.51 (1H, d, J = 2.7 Hz), 8.46 (1H, dd, J = 1.2 Hz, 2.7 Hz), 7.19 (1H, d, J = 1.8 Hz), 7.03 (1H, d, J = 1.8 Hz), 6.83 (1H, dd, J = 1.8 Hz, 8.7 Hz), 6.80 (1H, dd, J = 1.8 Hz, 8.4 Hz), 6.43 (1H, t, J = 4.5 Hz), 6.18 (1H, br), 5.96 (1H, d, J = 8.4 Hz), 5.05 (1H, br), 4.43 (2H, d, J = 4.5 Hz), 4.05 (1H, m), 3.92 (2H, m), 3.77 (1H, m).

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; BANYU PHARMACEUTICAL CO., LTD.; EP1666485; (2006); 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. 59489-32-6, name is 5-Chloro-2,3-dimethylpyrazine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 5-Chloro-2,3-dimethylpyrazine

To a degassed solution of 1,1-dimethylethyl (lR,4S,6R)-4-[(E/Z)-2-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)ethenyl]-3-azabicyclo[4.1.0]heptane-3-carboxylate D6 (150 mg) and 5-chloro-2,3-dimethylpyrazine D56 (73.5 mg) in 1,2- DME (3 ml) sodium carbonate 2M (1 ml, 2.000 mmol), dichloropalladium – triphenylphosphane (1 :2) (30.1 mg, 0.043 mmol) was added and the mixture was heated to 90C for 1.5 hours. The mixture was cooled down to room temperature, then diluted with EtOAc and washed with water and brine. Organic phase was dried over Na2S04, filtered and concentrated under reduced pressure. Crude was purified by flash chromatography on silica gel (Cy to Cy/EtOAc 1 : 1) affording the title compound D57 (26.6 mg).UPLC (IPQC): rt = 1.18 minutes peak observed: 330 (M+l) Ci9H27N302 requires 329.

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 59489-32-6.

Reference:
Patent; GLAXO GROUP LIMITED; DI FABIO, Romano; WO2012/89607; (2012); 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. 59489-71-3, name is 2-Amino-5-bromopyrazine, A new synthetic method of this compound is introduced below., Safety of 2-Amino-5-bromopyrazine

19.1. 5-aminopyrazine-2-carbonitrile Heat a suspension of 1.85 g (20.7 mmol) of copper cyanide and 1 g (20.7 mmol) of sodium cyanide in 20 ml of DMF to 135 C., while stirring. Add 3.6 g (20.7 mmol) of 5-bromopyrazin-2-amine to the solution obtained, and maintain the temperature of 135 C. for 18 h. Then add 2 equivalents of sodium cyanide and of copper cyanide and continue heating for a further 24 h. After cooling, add 100 mL of 0.3N aqueous solution of sodium cyanide, stir the mixture for 1 h at 40 C., then distribute it in 300 mL of EtOAc/water 1:1 mixture. After washing with 2*100 mL of water, dry the organic phase over Na2SO4 and concentrate under reduced pressure. Purify the residue obtained by silica gel column chromatography, eluding with a cyclohexane/EtOAc gradient from 0 to 100% of EtOAc. After concentration under reduced pressure, we obtain 1.24 g of 5-aminopyrazine-2-carbonitrile in the form of oil. Yield=50%

The synthetic route of 59489-71-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sanofi Aventis; US2009/318473; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 23611-75-8, 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. 23611-75-8, name is Methyl 6-chloropyrazine-2-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a stirred solution of 124 (1.5 g, 8.72 mmol) in NMP (10 vol) was added DIPEA (7.6 ml, 43.60 mmol) and /V-Boopiperazine (3.24 g, 17.44 mmol) at RT. The reaction mixture was stirred at 100 C for 16 h. The progress of the reaction was monitored by TLC. The reaction mixture was quenched with water and was extracted with ethyl acetate (3 x 100 ml). The combined organic layer was concentrated under reduced pressure to get the crude material. The crude compound was purified via column chromatography on silica-gel (100-200 mesh, 15-20 % EtOAc: Pet ether) to afford 125 (1 g, 35 %) as a colorless liquid. To a stirred solution of 125 (1 g, 3.10 mmol) in dry THF (10 mL) was added LiAIH4solution (2 in THF, 0.776 ml, 1.55 mmol) drop wise at -20 C and stirred at the same temperature for 2 h. The progress of the reaction was monitored by TLC. TLC showed formation of a polar spot with complete consumption of starting material. The reaction was quenched with saturated sodium sulphate and filtered the reaction mixture through a pad of celite. The filtrate was evaporated under reduced pressure to get the crude residue. The crude compound was purified via column chromatography on silica gel (100-200 mesh, 25 -28 % EtOAc: Pet ether) to afford 126 (500 mg, 54 %) as a pale yellow solid. To a stirred solution of 126 (500 mg, 1.70 mmol) in DC (10 vol) was added TEA (0.715 mL, 5.10 mmol) and methane sulfonyl chloride (0.197 mL, 2.55 mmol) drop wise at 0 C. The reaction mass was stirred at RT for 2 h. TLC showed formation of a non-polar spot with complete consumption of starting material. The reaction mixture was concentrated under reduced pressure to get 400 mg of crude 127 as a yellow syrup. The crude compound was as such used in the next step without any further purification. To a stirred solution of 6-103 (375.4 mg, 1.29 mmol) in D F (20 ml) was added K2C03(355.6 mg, 2.57 mmol) at RT and was stirred at RT for 10 min. Then 127 (400 mg, crude, 1 .075 mmol) in DMF was added drop wise at RT. The reaction mass was heated to 90 C for 16 h. The reaction mixture was quenched with ice cold water and was extracted into EtOAc (2 x 100 ml). The combined organic layers were washed with water, brine and dried over Na2S04.The solvent was removed under reduced pressure to get the crude material. The crude compound was purified by C-18 column with 0.01 % HCOOH in water and acetonitrile] and to afford 128 (95 mg, 10 %) as a white solid. To a stirred solution of 128 (90 mg, 0.158 mmol) in 1 ,4- dioxane (10 vol) was added 4 HCI-dioxane (10 mL) at 0 C. The reaction mixture was stirred at RT for 2 h. The solvent was removed under reduced pressure to get the residue, which was triturated with ether to get 85 mg of 6-205 as HCI salt.1H NMR (400 MHz, DMSO- d6): delta 9.14 (br s, 3H), 8.61 (br d, J = 7.8 Hz, 1 H), 8.36 (s, 1 H), 8.02 (s, 1 H), 7.40 – 7.31 (m, 1 H), 7.24 (d, J – 7.8 Hz, 1 H), 5.24 – 5.06 (m, 2H), 4.97 (s, 2H), 4.47 – 4.35 (m, 1 H), 3.90 – 3.76 (m, 4H), 3.17 (br s, 4H), 2.49 – 2.37 (m, 3H), 2.22 – 2.11 (m, 1 H), 0.97 (br d, J – 6.8 Hz, 6H). LC-MS: m/z 468.34 [M+H]+. HPLC purity: 95.10% (220 nm), 96.29% (254 nm) and chiral HPLC purity is 95.97% (247 nm).

The synthetic route of Methyl 6-chloropyrazine-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ANACOR PHARMACEUTICALS, INC.; AKAMA, Tsutomu; CARTER, David Scott; HALLADAY, Jason S.; JACOBS, Robert T.; LIU, Yang; PLATTNER, Jacob J.; ZHANG, Yong-Kang; WITTY, Michael John; (149 pag.)WO2017/195069; (2017); 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. 22047-25-2, name is Acetylpyrazine, This compound has unique chemical properties. The synthetic route is as follows., Safety of Acetylpyrazine

Preparation 21-Pyrazin-2-yl-ethylamineThe synthetic procedure used in this preparation is outlined below in Scheme C. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75%. MS (M+H)=124.

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 22047-25-2.

Reference:
Patent; Chen, Li; Dillon, Michael Patrick; Feng, Lichun; Yang, Minmin; US2010/324069; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 914452-71-4,Some common heterocyclic compound, 914452-71-4, name is 2-Bromo-6-methylpyrazine, molecular formula is C5H5BrN2, 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 the stirred solution of 2-bromo-6-methyl-pyrazine 51-3 (812 11 mg, 4.69 mmol) and methyl J – chloro-4-methyl-piperidine-4-carboxylate 51-2 (1000 mg, 5.16 mmol) in toluene (25 mL) was added cesium carbonate (4.59 g, 14.08 mmol). The reaction was degassed with argon for 10 minutes. Xanthphos (135 80 mg, 234.70 umoi) and Pd2(dba)3 (214 92 mg, 234.70 umoi) were added to the reaction mixture and the reaction mixture was heated at 90C for 16 hours. Reaction mixture was cooled to room temperature and diluted with ethyl acetate and water. Layers were separated and the organic layer was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. The crude material was purified by combiflash chromatography (eluting at 2 % methanol in di chi or om ethane) to afford methyl 4-methyl- 1 -(6- methylpyrazin-2-yl)piperi dine-4-carboxyl ate 51-4 (630 mg, 2.53 mmol, 53.83% yield) as brown gum. LC MS: ES+ 250.3.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-6-methylpyrazine, its application will become more common.

Reference:
Patent; C4 THERAPEUTICS, INC.; VEITS, Gesine, Kerstin; HE, Minsheng; HENDERSON, James, A.; NASVESCHUK, Christopher, G.; PHILLIPS, Andrew, J.; GOOD, Andrew, Charles; (471 pag.)WO2019/191112; (2019); 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 32111-21-0 as follows. HPLC of Formula: C4H3IN2

Example 42; Synthesis of Compound 76; Compound a from the synthesis of compound 74 (255 mg) was placed in an oven dried microwave reaction vial with CuI (53.3 mg) and K3PO4 (233.4 mg) and purged with N2. To this mixture was added iodopyrazine b and the vial purged again with N2 followed by addition of 1,2-cyclohexanediamine (62.8 mg) in 2.6 ml dioxane and N2 was bubbled into the solution for 10 min and the vial crimped. The reaction vial was placed in the microwave for 30 min. at 140 C. The reaction went to half completion and was worked up by filtering off the non-product solids, concentrating under vacuum, and purifying by flash to give 139 mg compound c (47% yield). Compound c was dissolved in 3 ml 1.0 M TBAF in THF and heated to 60 C. overnight. The reaction was completed by LCMS and was diluted with H2O, extracted with EtOAc, washed with brine, dried over MgSO4, concentrated under vacuum and purified by SFC to give the final compound 76.

According to the analysis of related databases, 32111-21-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Rawson, Thomas E.; Safina, Brian; Dotson, Jennafer; Zhou, Aihe; Aliagas-Martin, Ignacio; Halladay, Jason; Liang, Jun; Rueth, Matthias; Zhu, Bing-Yan; US2007/37791; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 6164-79-0, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 6164-79-0 name is Methyl 2-pyrazinecarboxylate, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

A solution of the product of Example 83A (6.91 g, 50 mmol) in THF (Aldrich, anhydrous, 150 mL) was cooled down to -78 C. and a solution of LiAlH4 (Aldrich, 1.898 g, 50.0 mmol) in THF (50 mL) was added slowly via an additional funnel. The mixture was stirred at -78 C. under N2 for 1 hour, and then it was then carefully and slowly quenched with HOAc (Aldrich, 10 mL) at -70 C. The mixture was slowly warmed up to ambient temperature and stirred for 10 hours. After being concentrated, the residue was stirred with HCl (2N, 15 mL) in CH2Cl2 (300 mL) for 20 minutes and then filtered through diatomaceous earth to remove solid inorganic salt. The organic filtrate solution was concentrated and the residue was dissolved in EtOAc (100 mL) and filtered through diatomaceous earth again. The organic filtrate solution was concentrated to give the titled compound. 1H NMR (300 MHz, DMSO-d6) delta 8.91 (dd, 1H), 8.94 (d, 1H), 9.12 (d, J=1.6 Hz, 1H), 10.08 (s, 1H) ppm; MS (DCI/NH3) m/z 109 (M+H)+.

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

Reference:
Patent; ABBOTT LABORATORIES; US2009/306096; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem