Category: 109838-85-9

Electric Literature of 109838-85-9, 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 109838-85-9 as follows.

Preparation 34: ((lS,2RV3-amino-l-(3,5-difluorotenzyl)-2-hydroxy-propyl)carbamic acid t-butyl esterStepA: (2S,5R)-2-(3,5-difluorobenzyl)-5-isopropyl-3,6-dimethoxy-2,5-dihvdropyrazine(R)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine was dissolved THF and n-BuLi was added thereto at -78 °C, followed by addition of difluorobenzyl chloride. After the reaction was complete, NH4Cl was added to the reaction mixture, followed by extraction with EtOAc. The organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: EtOAc: n-Hex = 1/1) to afford the title compound (339 mg, 80percent).MSbetaVI+l] = 313 (M+l)

According to the analysis of related databases, 109838-85-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; LG LIFE SCIENCES, LTD.; WO2009/38412; (2009); A2;,
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. 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

Step 1: Synthesis of Intermediate 1-4.1R8 (212 g, 1151 mmol) in tetrahydrofuran (dry) (600 mL) is cooled to -78°C. Then n-butyllithium(2.5 M in hexanes, 552 mL, 1381 mmol) is added dropwise, keeping the temperature below -78°C.After 30 mm R9 (324g, 1209 mmol) in tertahydrofuran (dry) (120 mL) is added dropwise. Thereaction mixture is stirred at -78°C for 1 h. The mixture is quenched with saturated NH4C1 solutionand extracted three times with ethyl acetate. The organic layer is washed with brine, dried overNa2SO4 and evaporated in vacuo. The residue is purified by flash chromatography (heptane/ ethyl acetate = 80/20). Yield 60percent.

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 109838-85-9.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; ANDERSKEWITZ, Ralf; GRAUERT, Matthias; GRUNDL, Marc; OOST, Thorsten; PAUTSCH, Alexander; PETERS, Stefan; WO2014/140091; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 109838-85-9, These common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, 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.

(S)-((2S,5R)-5-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazin-2-yl)(4-(trifluoromethyl)phenyl)methanol: To a mixture of (R)-2,5-dihydro-3,6-dimethoxy-2- isopropylpyrazine (5.2 tnL, 29 mmol)(commercially available from 3B Scientific Corporation Product List (Order Number 3B3-054672)) and THF (50 mL) at -78°C was added n-butyllithium (2.5 M solution in hexane, 12 mL, 31 mmol). The mixture was stirred for 15 minutes. The colorless solution turned light brown. A solution of 4- (trifluoromethyl)benzaldehyde (5.1 mL, 38 mmol)(commerciaHy available from 3B Scientific Corporation Product List (Order Number 3B4-3644)) in THF (50 mL) was added dropwise through a dropping funnel at -78°C. The mixture was stirred for 1 hour. The reaction mixture was diluted with EtOAc and washed with a mixed solution of aqueous Na2HPO4 and KH2PO4 solution (pH =8). The aqueous layer was extracted with EtOAc three times. The combined organic layers were washed with water and brine, dried over Na2SO4, and concentrated in vacuo. The crude residue was separated into two isomers by silica gel chromatography: 0-2percent- 10percent CH3CN-CH2CI2. The product was obtained as light yellow oil (2.3 g, 22 percent). LCMS (API-ES) m/z: 359 (M+H*).

The synthetic route of 109838-85-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMGEN INC.; WO2009/11871; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 109838-85-9, 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. 109838-85-9 name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, 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.

[0562] A solution of compound 4-01-5 (8.9 g, 48 mmol) in tetrahydrofuran (100 mL) was cooled to -70C and n-butyl lithium (2.5 M, 19.5 mL, 49 mmol) was added under nitrogen while the temperature was kept below -70C. A solution of compound 7- bromohept-l-ene (8.0 g, 45 mmol) in tetrahydrofuran (15 mL) was added at -70C. The reaction mixture was stirred at -70C for 2 hours, then slowly heated to 20C and stirred for 1 hour. The reaction mixture was poured into saturated ammonium chloride solution (50 mL) and extracted with ethyl acetate (200 mL *2). The combined organic phase was washed with brine (100 mL*2), dried over anhydrous sodium sulfate, and concentrated in reduced pressure. The residue was purified by column chromatography (petroleum ether to petroleum ether: ethyl acetate = 50: 1) to afford compound 4-01-6 (7 g, 55% yield) as a colorless oil.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, and friends who are interested can also refer to it.

Reference:
Patent; CORNELL UNIVERSITY; TRI-INSTITUTIONAL THERAPEUTICS DISCOVERY INSTITUTE; LIN, Gang; NATHAN, Carl; KIRKMAN, Laura; ZHAN, Wenhu; MORGAN, Trevor; SATO, Kenjiro; HARA, Ryoma; KAWASAKI, Masanori; IMAEDA, Toshihiro; TOITA, Akinori; OKAMOTO, Rei; YUKAWA, Takafumi; ASO, Kazuyoshi; WONG, Tzu-Tshin; GINN, John, D.; FOLEY, Michael, A.; (296 pag.)WO2019/75259; (2019); 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. 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, A new synthetic method of this compound is introduced below., Application In Synthesis of (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

To a solution of (R)-2-isopropyl-3, 6-dimethoxy-2, 5-dihydropyrazine (500 mg, 2.72 mmol) and bis(chloromethyl) dimethylsilane (636 mg, 4.08 mmol) in THF (10 mL) under N2atmosphere in a dry ice/acetone bath was slowly n-BuLi (1.6 M in hexane, 2 mL, 3.2 mmol) via an injection syringe. After addition, the reaction was stirred at room temperature overnight. The reaction mixture was cooled to 0° C. and quenched by dropwise addition of water. The resulting mixture was extracted with EtOAc. The organic layer was washed by brine, dried over anhydrous Na2SO4and concentrated. The obtained crude product was purified by column chromatography on silica gel eluted with PE/EtOAc (100:1 to 30:1) to give the title compound (640 mg, 77.5percent yield); LC/MS (ESI) m/z: 305 [M+H]

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; ACHILLION PHARMACEUTICALS, INC.; WILES, Jason, Allan; PHADKE, Avinash, S.; DESHPANDE, Milind; AGARWAK, Atul; CHEN, Dawei; GADHACHANDA, Venkat, Rao; HASHIMOTO, Akihiro; PAIS, Godwin; WANG, Qiuping; WANG, Xiangzhu; (905 pag.)WO2017/35353; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, 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 109838-85-9, name: (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

Step B – Preparation of Compound Int-15b Int-15bTo a solution of (2R)-(-)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (0.61 g, 4.36 mmol) in THF (8 mL) was added n-BuLi (2.5 M in hexane, 1.8 mL, 4.58 mmol) at -78 °C. After allowed to stir for 0.3 hours, Compound Int-15a (2.75 g, 6.98 mmol) in 2 mL of THF was added and the mixture was allowed to stir at the temperature for 4 hours. The reaction was quenched by saturated aqueous H4C1 solution and the organic layers were extracted with EtOAc. The combined organic solution was washed with brine solution, dried (Na2S04), and concentrated in vacuo. The residue obtained was purified using ISCO 40 g column (gradient from 0percent to 2.5percent ether in hexane) to provide Compound Int-15b, 783 mg (44percent). 1H MR (CDC13) delta 4.05 (m, 1H), 3.96 (t, J= 3.4 Hz, 1H), 3.72 (s, 3H), 3.71 (s, 3H), 3.49 (dd, 7= 2,8, 0.4 Hz, 1H), 3.26 (dd, 7= 6, 9.4 Hz, 1H), 2.30 (m, 1H), 1.96 (m, 1H), 1.60 (m, 2H), 1.37-1.17 (m, 3H), 1.08 (d, 7= 6.9 Hz, 3H), 0.99-0.86 (m, 2H), 0.72 (d, 7= 6.6 Hz, 3H), 0.49 (dd, 7= 11.0, 14.4 Hz, 1H), 0.35 (dd, 7= 11.0, 14.2 Hz, 1H), 0.16 (s, 6H).

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.; DWYER, Michael P; KEERTIKAR, Kartik M; COBURN, Craig A; WU, Hao; HU, Bin; ZHONG, Bin; ZHANG, Chengren; DAN, Zhigang; TONG, Ling; YU, Wensheng; WO2012/41227; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 109838-85-9, The chemical industry reduces the impact on the environment during synthesis 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, I believe this compound will play a more active role in future production and life.

Preparation 13: [(lS2RV3-arnino-l-(315-Muoro-bemyl)-2-hydroxy-propyl]-carbarnic acid t-butyl ester Step A: (2S,5RV2,5-dihvdro-3,6-dimethoxy-5-isopropyl-2-(3,5-dMuoro)benzylpyrazine(TR.)-2,5-dihydro-3,6-dirnethoxy-2-isopropylpyrazine (9.2 g, 50 mmol) was dissolved in THF (100 mL), to which n-BuLi (4M in THF, 15 mL) was then added at -78 °C, followed by addition of difluorobenzyl chloride (9.72 g, 60 mmol). After the reaction was complete, NH4Cl was added to the reaction mixture which was then extracted with EtOAc. The organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography (EtOAc: n-Hex = 1/1) to afford the title compound (12.4 g, 80percent).

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, (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; LG LIFE SCIENCES, LTD.; WO2009/38411; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, 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. name: (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

Step B – Syntheses of Intermediate Compound Int-31b (0407) (0408) To a -78 °C solution of (2R)-(-)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (0.61 g, 4.36 mmol) in THF (8 mL) was added n-BuLi (2.5 M in hexane, 1.8 mL, 4.58 mmol). The resulting reaction was allowed to stir for 20 minutes, then Compound Int-31a (2.75 g, 6.98 mmol, in 2 mL of THF) was added and the reaction was allowed to stir at -78 °C for 4 hours. The reaction was quenched with saturated aqueous NH4Cl solution and the organic layers were extracted with EtOAc. The combined organic solution was washed with brine solution, dried (Na2SO4), filtered and concentrated in vacuo. The resulting residue was purified using an ISCO 40 g column (gradient from 0percent to 2.5percent ether in hexane) to provide Compound Int-31b, 783 mg (44percent). 1H NMR (CDCl3) delta 4.05 (m, 1H), 3.96 (t, J = 3.4 Hz, 1H), 3.72 (s, 3H), 3.71 (s, 3H), 3.49 (dd, J = 2,8, 0.4 Hz, 1H), 3.26 (dd, J = 6, 9.4 Hz, 1H), 2.30 (m, 1H), 1.96 (m, 1H), 1.60 (m, 2H), 1.37-1.17 (m, 3H), 1.08 (d, J = 6.9 Hz, 3H), 0.99-0.86 (m, 2H), 0.72 (d, J = 6.6 Hz, 3H), 0.49 (dd, J = 11.0, 14.4 Hz, 1H), 0.35 (dd, J = 11.0, 14.2 Hz, 1H), 0.16 (s, 6H).

The synthetic route of (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Merck Sharp & Dohme Corp.; Nair, Anilkumar Gopinadhan; Keertikar, Kerry M.; Kim, Seong Heon; Kozlowski, Joseph A.; Rosenblum, Stuart; Selyutin, Oleg B.; Wong, Michael; Yu, Wensheng; Zeng, Qingbei; EP2545060; (2015); B1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 109838-85-9, These common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, 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 L- 3 necked round bottomed flask, equipped with a mechanical stirrer, temperature probe, addition funnel and N2 inlet, was charged with the Schollkopf chiral auxiliary-(Int-13a, 200 g, 1.09 mol, 1.0 eq), bis(chloromethyl) dimethylsilane (Int-13b, 256 g, 1.63 mol, 1.5 eq), and THF (2 L, Aldrich anhydrous). The flask was cooled in a dry ice/ 2- propanol bath until the internal temperature reached -75 °C. n-Butyllithium (Aldrich 2.5 M in hexanes , 478 mL, 1.19 mol, 1.09 eq) was added via a dropping funnel over 1 hour while maintaining the internal reaction temperature between -67 °C and -76 °C. The resulting orange-red solution was allowed to gradually warm to room temperature for about 15 hours. The reaction mixture was then re-cooled to 0 °C and quenched with 500 mL of water.Diethyl ether (2L) was added and the layers were separated. The aqueous layer was extracted with 1 L of diethyl ether. The combined organic extracts was washed with water and brine, dried with MgS04, filtered, and concentrated in vacuo to dryness, giving 480 g of orange oil. This material was left in vacuo for about 15 hours to provide 420 g of oil. The crude product was split into two batches and purified via silica gel chromatography on a 1.6 kg flash column. The column was eluted with gradient of 0-4percent Et20 in hexanes. The product fractions were concentrated in vacuo at a bath temperature at or below 40 °C giving 190 grams of Int-13c-(60percentyield).

The synthetic route of 109838-85-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SCHERING CORPORATION; COBURN, Craig, A.; LAVEY, Brian, J.; DWYER, Michael, P.; KOZLOWSKI, Joseph, A.; ROSENBLUM, Stuart, B.; WO2012/50848; (2012); 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. 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 109838-85-9

A 5 L- 3 necked round bottomed flask, equipped with a mechanical stirrer, temperature probe, addition funnel and N2 inlet, was charged with the Schollkopf chiral auxiliary-(Int-13a, 200 g, 1.09 mol, 1.0 eq), bis(chloromethyl) dimethylsilane (Int-13b, 256 g, 1.63 mol, 1.5 eq), and THF (2 L, Aldrich anhydrous). The flask was cooled in a dry ice/ 2- propanol bath until the internal temperature reached -75 °C. n-Butyllithium (Aldrich 2.5 M in hexanes , 478 mL, 1.19 mol, 1.09 eq) was added via a dropping funnel over 1 hour while maintaining the internal reaction temperature between -67 °C and -76 °C. The resulting orange-red solution was allowed to gradually warm to room temperature for about 15 hours. The reaction mixture was then re-cooled to 0 °C and quenched with 500 mL of water.Diethyl ether (2L) was added and the layers were separated. The aqueous layer was extracted with 1 L of diethyl ether. The combined organic extracts was washed with water and brine, dried with MgS04, filtered, and concentrated in vacuo to dryness, giving 480 g of orange oil. This material was left in vacuo for about 15 hours to provide 420 g of oil. The crude product was split into two batches and purified via silica gel chromatography on a 1.6 kg flash column. The column was eluted with gradient of 0-4percent Et20 in hexanes. The product fractions were concentrated in vacuo at a bath temperature at or below 40 °C giving 190 grams of Int-13c-(60percentyield).

According to the analysis of related databases, 109838-85-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; KOZLOWSKI, Joseph, A; ROSENBLUM, Stuart, B; COBURN, Craig, A; SHANKAR, Bandarpalle, B; ANILKUMAR, G, Nair; CHEN, Lei; DWYER, Michael, P; JIANG, Yueheng; KEERTIKAR, Kartik, M; LAVEY, Brian, J; SELYUTIN, Oleg, B; TONG, Ling; WONG, Michael; YANG, De-Yi; YU, Wensheng; ZHOU, Guowei; WU, Hao; HU, Bin; ZHONG, Bin; SUN, Fei; JI, Tao; SHEN, Changmao; WO2012/40923; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem