Category: 109838-85-9

Synthetic Route of 109838-85-9,Some common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, molecular formula is C9H16N2O2, 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.

b) 2,5-Dihydro-3,6-dimethoxy-2-isopropyl-5-(2′-iodo-4′-methoxybenzyl)- (2R,5S)-pyrazine (21); The diastereomeric product 21 was obtained by a reaction of the lithium salt of the chiral auxiliary (2R)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine with the bromo derivative 20 using a crucial modification of a procedure reported in the literature [U. Schollkopf, “Enantioselective Synthesis of Non-Proteinogenic Amino Acids via Metallated Bis-Lactim Ethers of 2,5-Diketopiperazines.” Tetrahedron, 39, pp 2085- 2091 (1983)]. Briefly, (2R)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (4.39 mL, 24.5 mmol) was dissolved in 4 mL of THF (freshly distilled from LiAlH4). The light yellow solution was cooled to -78° C (dry ice/acetone bath) and stirred for 15 min under argon. A 2.5 M solution of n-butyl lithium (9.79 mL, 24.5 mmol) was added drop wise over a period of 10 min and the mixture was stirred for 20 min at – 78° C. In a separate flask CuCN (1.096 g, 12.23 mmol) was stirred with 4 mL of freshly distilled THF at room temperature for 10 min. The white suspension was then cooled to 0° C (ice bath) and stirred at that temperature for 20 min. The n-BuLi reaction mixture was then transferred to the white suspension of CuCN/THF under argon using a cannula. The resulting yellow suspension turned into a yellow solution within two minutes. The reaction mixture was then stirred at 0° C for 15 min and cooled to -78° C. After 15 min of stirring at -78° C, a solution of bromomethyl anisole derivative 20 (4.00 g, 12.23 mmol) in 6 mL of freshly distilled THF was added drop wise. The color of the reaction mixture changed to greenish brown. After stirring for a further period of 2 hours at -78° C, the reaction mixture was warmed gradually to room temperature. The reaction mixture was then poured into a saturated solution of NH4Cl and extracted with EtOAc. The organic phase was dried over anhydrous Na2SO4, filtered and evaporated to provide an oily compound which was purified by flash column chromatography to yield pure 2,5-Dihydro-3,6-dimethoxy-2- isopropyl-5-(2-iodo-4-methoxybenzyl)-(2R,5S)-pyrazine (21) as a yellow oil (3.95 g,percent).1H NMR (CDCl3): delta 7.34 (d, IH, H-31), 7.1 (d, IH, H-61), 6.80 (dd, IH, H-51), 4.25 (dd, IH, H-5), 3.75 (s, 3H, 4′-OMe), 3.73 (s, 3H, 6-0Me), 3.70 (d, IH, H-2), 3.60 (s, 3H, 3-OCH3), 3.60, 2.95 (dd, 2H, CH2), 2.20 (m, IH, CH of isopropyl), 1.00 ( d, 3H, CH3), 0.60 ( d, 3H, CH3). 13C NMR (CDCl3): delta 163.72 (C-3), 163.10 (C-6), 158.23 (C-41), 133.22 (C-I’), 130.84(C-61), 124.23 (C-31), 114.00 (C-51), 101.50 (C-21), 60.47 (C-2), 56.30 (C-5), 55.38 (41-OCH3), 52.54 (6-OCH3), 52.39 (3-OMe), 43.63 (CH2), 31.40 (CH of isopropyl), 19.06(CH3), 16.55 (CH3).MS (ESI) Calcd for CnH23IN2O3 (M+): 430.08; Found: 431.07 (M++l).Figure 15 shows the C-13/H-1 HMBC NMR spectrum of compound 21.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, its application will become more common.

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; SATYAMURTHY, Nagichettiar; BARRIO, Jorge, R.; WO2010/8522; (2010); 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. Safety of (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

General procedure: Butyl lithium (1.6 N solution in hexane, 1.05 equiv) was added to a solution of (2R)-1 (1 equiv) in anhydrous THF (5 mL) cooled to ?78°C, and the mixture was stirred for 45 min. Imine 2a?f (1 equiv) in THF (4 mL) was added, and the mixture was stirred at ?78°C for 8h. The reaction mixture was allowed to warm to ?10 °C, after which a pH=7 phosphate buffer solution (10 mL) was added, and the mixture was extracted with ethyl acetate (3×10 mL). The organic phase was separated and dried with Na2SO4, and the solvent was evaporated in vacuo. Compounds 3, 4 were purified by means of flash chromatography (SiO2, CH2Cl2/hexane=40/60 for 3a (Rf 0.2) and 4a (Rf 0.4); CH2Cl2/ethyl acetate=95/5 for 3d (Rf 0.4) and 4d (Rf 0.5), 3e (Rf 0.5) and 4e (Rf 0.6); CH2Cl2/ethyl acetate=98/2 for 4f (Rf 0.6)).

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:
Article; Cremonesi, Giuseppe; Dalla Croce, Piero; Gallanti, Maddalena; La Rosa, Concetta; Tetrahedron; vol. 70; 11; (2014); p. 2054 – 2058;,
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, Formula: C9H16N2O2

At -78° C. 7.80 ml (19.5 mmol) n-butyllithium (2.5 M in hexane) were added dropwise to 2.90 ml (16.2 mmol) (R)-2-isopropyl-3.6-dimethoxy-2,5-dihydropyrazine in 55 ml THF and the mixture was stirred for 2 h at -50° C. Then at -70° C. 4.25 g (17.8 mmol) (iodomethyl)cycloheptane in 15 ml THF were added dropwise, then the mixture was stirred for 30 min at -78° C., for 3 h at 0° C. and overnight at RT. After the addition of water and methanol it was stirred for 20 min at RT. Ethyl acetate was added and the mixture was extracted with saturated, aqueous saline solution. The organic phase was dried and evaporated to dryness by rotary evaporation. The residue was purified by flash chromatography. The fractions containing the product were combined and concentrated by rotary evaporation. The residue obtained was combined with acetonitrile, water and 1M hydrochloric acid and stirred overnight at RT. The acetonitrile was evaporated off and the aqueous phase was neutralised with potassium hydrogen carbonate. It was extracted with ethyl acetate. The combined organic phases were dried and evaporated to dryness by rotary evaporation.Yield: 1.04 g (32percent of theoretical)ESI-MS: m/z=200 (M+H)+ Rt (HPLC): 0.96 min (method A)The enantiomeric (R)-compound may be obtained analogously to the method of synthesis described above using the corresponding (R)-configured reaction component.

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; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; US2012/196872; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 109838-85-9, 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.

To a 100 ml three neck round bottomed flask under nitrogen atmosphere, (R)-2- isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (4 g, 21.7 mmol) was dissolved in dry THF (28 ml) and cooled to -78 C. To this reaction mixture, 1 .6 M solution of n-BuLi in hexanes (16.3 ml, 26 mmol) was added dropwise at -78 C and stirred for 15 minutes. A solution of l-bromo-3- (2-bromoethyl)benzene (5.73 g, 21 .7 mmol) in dry THF (13 ml) was added dropwise at -78 C and stirred for 1 h followed by stirring at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted using ethyl acetate. The combined organic layer was dried over sodium sulfate and concentrated and purified by flash column purification with 1 -3 % ethyl acetate in hexanes to yield 3.3 g of (2S,5R)-2-(3-bromophenethyl)-5-isopropyl- 3,6-dimethoxy-2,5-dihydropyrazine.

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

Reference:
Patent; BRAMELD Kenneth; OWENS Timothy; WO2015/195950; A1; (2015);,
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., Computed Properties of C9H16N2O2

Step 4: (2S,5R)-2-(3-(Benzyloxy)-5-bromopentyl)-5-isopropyl-3,6-dimethoxy-2,5- dihydropyrazine (S6) [0523] To a dry-ice / acetone cooled solution of scheme 5-8 compound S5 (5 g, 0.027 mol) in THF (50 ml), was dropwise added n-BuLi (2.5 M, 14.1 mL, 0.035 mol) for 30 min. After addition, the reaction was stirred at this temperature for 30 min, followed by dropwise addition of a solution of scheme 5-8 compound S4 (13.6 g, 0.04 mol) in THF (20 mL). The reaction mixture was stirred at this temperature for another 30 min and allowed to stir at room temperature for 16 h. Then the reaction was quenched with aq. H4CI (50 mL) and extracted with ethyl acetate (60 mL x 2). The combined organic layers are washed with brine, dried over anhydrous Na2SC”4, filtered and then concentrated. The residue was purified by column chromatography on silica gel (eluted with petroleum ether: ethyl acetate =10: 1) to give the title compound (6 g, yield 50.4%>) and scheme 5-8 compound S4 (4.8 g) was recovered.

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; ACHILLION PHARMACEUTICALS, INC.; WILES, Jason, Allan; PHADKE, Avinash, S.; DESHPANDE, Milind; AGARWAL, Atul; CHEN, Dawei; GADHACHANDA, Venkat, Rao; HASHIMOTO, Akihiro; PAIS, Godwin; WANG, Qiuping; WANG, Xiangzhu; GREENLEE, William; (317 pag.)WO2017/35413; (2017); 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., Product Details of 109838-85-9

1.1) (2S,5R)-2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-isopropyl-3,6-dimethoxy-2,5-dihydro-pyrazine (Intermediate 1):Commercially available (R)-2-isopropyl-3,6-dimethoxy-2,5-dihydro-pyrazine (2.Og, 10.86 mmol) in dry THF (12ml) under argon was cooled to -75°C. n-BuLi (8 ml, 13.03 mmol, 1.6M solution in hexanes) was added slowly and stirring was continued for 30 min. After that 3-bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole (3.628 g, 13.03 mmol), (preparation described in J. Med. Chem. 2005, 4511-4525; Bioorg. Med. Chem. Lett. 2004, 4191-4195), in THF (15 ml) was added dropwise under stirring and stirring was continued for 30 min at -75 °C. Then the mixture was warmed to 0 °C and stirred for 1h before it was quenched with sat. aq. NaHCO3-solution. The mixture was extracted with ethyl acetate, the organic layers were combined and dried with MgSO4, filtered and evaporated to dryness. A crude oil was obtained (4.1 g) and the diastereomeric excess (d.e.: 88 percent) was determined by H-NMR from that crude mixture. The mixture was separated by column chromatography on silica gel (n- heptane-ethyl acetate 6:1). Yield: 3.3 g, 80 percent.

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; SANOFI-AVENTIS; WO2009/103439; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 109838-85-9,Some common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, molecular formula is C9H16N2O2, 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.

Synthesis of Intermediate Compound Int-8d(i?)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine (Int-8c, 25 g,135.7 mmol) and dried THF (500 mL) were added to a dried 1 -liter flask which was cooled to -78 °C and maintained under nitrogen atmosphere. A solution of 2.5 M n-BuLi in hexane (54 mL, 135 mmol) was added slowly via a syringe. The resulting solution was allowed to stir at the cold temperature for 30 minutes before addition of Int-8b (90.5 g, 266.2 mmol) via a syringe. The reaction mixture was continued to stir for 4 hours and warmed to room temperature gradually over a period of 1 hour. After addition of water (100 mL) and diethyl ether (1.0 liter), the solution was washed with water (2 x 200 mL) and dried over sodium sulfate. The solution was concentrated in vacuo and the residue obtained was purified using a 330 g ISCO silica column on Combi-Flash with 0-1percent ether in hexanes as an eluent to provide Int-8d as an oil (18.5 g, 35percent).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; DWYER, Michael, P.; KEERTIKAR, Kartik, M.; ZENG, Qingbei; MAZZOLA, Robert, D., Jr.; YU, Wensheng; TANG, Haiqun; KIM, Seong Heon; TONG, Ling; ROSENBLUM, Stuart, B.; KOZLOWSKI, Joseph, A.; NAIR, Anilkumar Gopinadhan; WO2013/39876; (2013); 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. 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Quality Control of (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

A solution of (2R)-(-)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (4.25 g, 23.1 mmol) in tetrahydrofuran (30 ml) was cooled to -78° C., then n-butyllithium (1.6 M in hexane, 15.1 ml, 24.2 mmol) was added and the mixture was stirred for 1 hour. A solution of ((R)-1-iodomethyl-propyl)-benzene (6.30 g, 24.2 mmol) in tetrahydrofuran (30 ml) was added dropwise over 30 min and the mixture was stirred overnight while being allowed to warm slowly from -70° C. to room temperature. The reaction was quenched by addition of saturated aqueous ammonium chloride solution and the mixture was extracted with ether. The organic layer was separated, washed with saturated brine, then dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (SiO2, heptane/EtOAc) to yield a light yellow oil (4.69 g, 64percent); MS (ISP): 317.0 ([M+H]+).

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

Reference:
Patent; HOFFMANN-LA ROCHE INC.; Hoener, Marius; Raab, Susanne; Risterucci, Celine; Sewing, Sabine; US9132136; (2015); B2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 109838-85-9, 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. 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

Step B – Synthesis of Intermediate Compound Int-32c (0421) To a 500 mL flame dried flask was added (R)-2-isopropyl-3, 6-dimethoxy-2,5-dihydropyrazine (10.0 g, 54.3 mmol) and anhydrous THF (200 mL). The solution was cooled to -78 °C. n-BuLi (2.5M in hexane, 24.0 mL, 59.7 mmol) was added dropwise. After the solution was allowed to stir at -78 °C for 30 minutes, Int-32b (in 5 mL anhydrous THF) was added dropwise. After the solution was allowed to stir at -78 °C for 1 hour, it was allowed to warm up to room temperature in two hours. Water (100 mL) and Et2O (150 mL) were added. The organic layer was separated and the aqueous layer was extracted with Et2O (100 mL) twice. The organic layers were combined, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The resulting residue was purified using flash chromatography on silica gel (40 g, eluted with Et2O in Hexane: 0percent to 3percent) to provide Compound Int-32c (10.43 g, 58.0percent).

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; 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

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, Product Details of 109838-85-9

(2R)-(?)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine (212 g, 1151 mmol) in dry tetrahydrofuran (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 min 4-bromo-2-fluorobenzyl bromide (324 g, 1209 mmol) in dry tetrahydrofurane (120 mL) is added dropwise. The reaction mixture is stirred at ?78° C. for 1 h. The mixture is quenched with saturated NH4Cl solution and extracted three times with ethyl acetate. The organic layer is washed with brine, dried over Na2SO4, filtered and evaporated in vacuo. The residue is purified by flash chromatography (heptane/ethyl acetate=80/20). Yield 60percent.

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; Boehringer Ingelheim International GmbH; VINTONYAK, Viktor; GRAUERT, Matthias; GRUNDL, Marc; PAUTSCH, Alexander; (64 pag.)US2016/75704; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem