Continuously updated synthesis method about (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

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.

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., HPLC of Formula: C9H16N2O2

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¡ãC, 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¡ãC for 8h. The reaction mixture was allowed to warm to ?10 ¡ãC, after which a pH=7 phosphate buffer solution (10 mL) was added, and the mixture was extracted with ethyl acetate (3¡Á10 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)).

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:
Article; Cremonesi, Giuseppe; Dalla Croce, Piero; Gallanti, Maddalena; La Rosa, Concetta; Tetrahedron; vol. 70; 11; (2014); p. 2054 – 2058;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Share a compound : (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

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.

Electric Literature 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.

Step A – Preparation of Compound Int- 13cA 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 ¡ãC. 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 ¡ãC and -76 ¡ãC. 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 ¡ãC 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 layers 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 ¡ãC giving 190 grams of Int-13c-(60percentyield).

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; COBURN, Craig A; WU, Hao; HU, Bin; ZHONG, Bin; ZHANG, Chengren; DAN, Zhigang; WO2012/40924; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A new synthetic route of (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

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.

Application 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.

Step A – Synthesis of Intermediate Compound Int-6cA 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-6a, 200 g, 1.09 mol, 1.0 eq), bis(chloromethyl) dimethylsilane (Int-6b, 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 ¡ãC. n-Butyl lithium (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 ¡ãC and -76 ¡ãC. 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 ¡ãC 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 layers was washed with water and brine, dried with MgS04, filtered, and concentrated in vacuo to provide 480 g of an orange oil. This material was left in vacuo for about 15 hours to provide 420 g of oil (mixture of Int-6c and Int-6c’). 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 ¡ãC to provide 190 grams of Compound Int-6c (60percent yield).

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

Simple exploration of (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

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

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

Step B – Preparation of Compound Int-16cTo 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 ¡ãC. “-BuLi (2.5M in hexane, 24.0 mL, 59.7 mmol) was added dropwise. After the solution was allowed to stir at -78 ¡ãC for 30 minutes, compound Int-16b (in 5 mL anhydrous THF) was added dropwise. After the solution was allowed to stir at -78 ¡ãC for 1 hour, it was allowed to warm up to room temperature in two hours. Water (100 mL) and Et20 (150 mL) were added. The organic layer was separated and the aqueous layer was extracted with Et20 (100 mL) twice. The organic layers were combined, washed with brine, dried over Na2S04, filtered and concentrated in vacuo. The residue obtained was purified using Si02 chromatography (40 g, eluted with Et20 in Hexane: 0percent to 3percent) to provide compound Int-16c (10.43 g, 58.0percent).

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

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; WO2012/40924; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some tips on 109838-85-9

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.

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. category: Pyrazines

To a dry-ice / acetone cooled solution of scheme 5-8 compound S5 (5 g, 0.027 mol) in THF (50 ml), n-BuLi (2.5 M, 14.1 mL, 0.035 mol) was added dropwise for 30 min. After addition, the reaction was stirred at this temperature for 30 min, followed by dropwise addition of a solution of 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 aqeuous NH4Cl (50 mL) and extracted with ethyl acetate (60 mL x 2). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and then concentrated. The residue was purified by column chromatography on silica gel (eluted with petroleum ether: ethyl acetate =10:1) to afford the title compound (6 g, yield 50.4%) and scheme 5-8 compound S4 (4.8 g) was recovered.

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; 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; (508 pag.)WO2017/35409; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Research on new synthetic routes about 109838-85-9

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 109838-85-9, its application will become more common.

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. Safety of (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

(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 (8.0 mL, 45 mmol, Fluka catalog number 37286-5mL) and THF (60 mL) at -78 0C was added n-butyllithium (2.5 M solution in hexane, 19 mL, 47 mmol). The mixture was stirred for 15 minutes. The colorless solution turned light brown. Then a solution of 4-(trifluoromethyl)benzaldehyde (Aldrich, 7.2 mL, 54 mmol) in THF (60 mL) was added dropwise through a dropping funnel at -78 0C. The mixture was stirred for 1 hour after addition was complete. 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, filtered, and concentrated in vacuo. The initial product was separated into two isomers by silica gel chromatography (O – 2 percent – 10 percent ACN-DCM). The desired product was obtained as an off-white solid (6.40 g, 40 percent). LCMS (API-ES) m/z (percent): 359 (M++H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 109838-85-9, its application will become more common.

Reference:
Patent; AMGEN INC.; ZENG, Qingping; YUAN, Chester Chenguang; YAO, Guomin; WANG, Xianghong; TADESSE, Seifu; ST. JEAN, JR., David J.; REICHELT, Andreas; LIU, Qingyian; HONG, Fang-Tsao; HAN, Nianhe; FOTSCH, Christopher H.; DAVIS, Carl D.; BOURBEAU, Matthew P.; ASHTON, Kate S.; ALLEN, John G.; WO2010/83246; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Extended knowledge of 109838-85-9

Statistics shows that (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine is playing an increasingly important role. we look forward to future research findings about 109838-85-9.

Reference 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.

Step A – Synthesis of Intermediate Compound Int-6c 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-6a, 200 g, 1.09 mol, 1.0 eq), bis(chloromethyl) dimethylsilane (Int-6b, 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 ¡ãC. n-Butyl lithium (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 ¡ãC and -76 ¡ãC. 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 ¡ãC 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 layers was washed with water and brine, dried with MgS04, filtered, and concentrated in vacuo to provide 480 g of an orange oil. This material was left in vacuo for about 15 hours to provide 420 g of oil(mixture of Int-6c and Int-6c’). 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 ¡ãC to provide 190 grams of Compound Int-6c (60percent yield).

Statistics shows that (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine is playing an increasingly important role. we look forward to future research findings about 109838-85-9.

Reference:
Patent; MERCK SHARP & DOHME CORP.; DWYER, Michael, P.; KEERTIKAR, Kartik, M.; ZENG, Qingbei; MAZZOLA, Robert, D., Jr.; CALDWELL, John, P.; TANG, Haiqun; NAIR, Anilkumar Gopinadhan; SHANKAR, Bandarpalle, B.; ROSENBLUM, Stuart, B.; KOZLOWSKI, Joseph, A.; WO2013/39878; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A new synthetic route of 109838-85-9

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.

Related Products 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.

Step A – Synthesis of Intermediate Compound Int-23c (0372) 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-23a, 200 g, 1.09 mol, 1.0 eq), bis(chloromethyl) dimethylsilane (Int-23b, 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 ¡ãC. n-Butyl lithium (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 ¡ãC and -76 ¡ãC. The resulting orange-red solution was allowed to gradually warm to room temperature for about 15 hours. The reaction mixture was then recooled to 0 ¡ãC 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 layers was washed with water and brine, dried with MgSO4, filtered, and concentrated in vacuo to provide 480 g of an orange oil. This material was left under vacuum for about 15 hours to provide 420 g of oil (mixture of Int-23c and Int-23c’). 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 Et2O in hexanes. The product fractions were concentrated in vacuo at a bath temperature at or below 40 ¡ãC to provide 190 grams of Compound Int-25c-(60percent yield).

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.; 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

Some tips on 109838-85-9

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.

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.

(2S,5R)-2-((2,3-Dihydrobenzo[b][l,4]dioxin-6-yl)methyl)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine. n-BuLi (57 mL, 142 mmol, Aldrich) was added dropwise to a solution of (R)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (24 g, 132 mmol) in THF (200 mL) at -78 0C under N2, and the mixture was stirred at the same temperature for 40 minutes. A solution of 6-(bromomethyl)-2,3- dihydrobenzo[b][l,4]dioxine (27 g, 118 mmol) in THF (160 mL) was added dropwise, and the resulting mixture was stirred at -78 0C for an additional 2 hours. The reaction was quenched by addition of saturated aqueous NH4Cl (200 mL). The THF was then removed under reduced pressure, and the resulting mixture was partitioned between EtOAc (300 mL) and H2O (300 mL). The organic layer was separated, washed with brine (300 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with petroleum ether/EtOAc (100: 1 to 30: 1) to afford (2S,5R)-2-((2,3-dihydrobenzo[b][l,4]dioxin-6-yl)methyl)-5-isopropyl-3,6- dimethoxy-2,5-dihydropyrazine (34 g, 73 percent). LCMS (API-ES) m/z 333.2 (M+H+).

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; AMGEN INC.; ZENG, Qingping; YUAN, Chester Chenguang; YAO, Guomin; WANG, Xianghong; TADESSE, Seifu; ST. JEAN, JR., David J.; REICHELT, Andreas; LIU, Qingyian; HONG, Fang-Tsao; HAN, Nianhe; FOTSCH, Christopher H.; DAVIS, Carl D.; BOURBEAU, Matthew P.; ASHTON, Kate S.; ALLEN, John G.; WO2010/83246; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A new synthetic route of 109838-85-9

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 109838-85-9, its application will become more common.

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. COA of Formula: C9H16N2O2

DMSO (1.95 g, 1.64 mL, 25.0 mmol) was added dropwise to a solution of oxalyl chloride (1.52 g,1.05 mL, 12.0 mmol) in CH2Cl2 at -78 0C. After stirring at -78 0C for 15 min, 4-phenyl-l-butanol (1.50 g, 1.52 mL, 10.0 mmol) was added dropwise. After 15 min, triethylamine (5.05 g, 6.96 mL) was added dropwise. After warming to r.t. over 2 hours, water (50 mL) was added and the solution was extracted with CH2Cl2 (4 X 50 mL). The combined organic phase was washed with HCl (0.25 N, 3 X 50 mL), water (50 mL), saturated NaHCO3, and brine. The organic extract was dried over Na2SO4, concentrated, and passed through a short silica column (2 x 3 cm), eluted with CH2Cl2. Solvent was removed to give 4-phenylbutanal as a colorless oil (1.30 g, 87percent). 1H NMR (500 MHz, CDCl3) delta 9.76 (t, / = 1.5 Hz, 1 H), 7.31-7.27 (m, 2 H), 7.22-7.17 (m, 2 H), 2.67 (t, / = 7.5 Hz, 2 H), 2.46 (dt, J = 1.6, 7.32 Hz, 2 H), 1.97 (m, 2 H).[000199] To a solution of the bislactim (R)-2-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (1.842 g, 1.792 mL, 10.0 mmol) in THF (20 mL) at -78 0C was slowly added n-BuLi (6.875 mL, 1.6 M in hexanes, 11.0 mmol) under Ar. After stirring at -78 0C for 20 min, A methyl iodide solution (1.562 g, 0.686 mL, 11.0 mmol) in THF (5 mL) was added. It was stirred at -78 0C for 2 h. A further portion of n-BuLi (6.25 mL, 1.6 M in hexanes, 10.0 mmol) was added at -78 0C and the solution was warmed to 0 0C. A solution of SnCl2 (1.0 g, 5.3 mmol) in THF (20 mL) was added and stirred at 0 0C for 15 min. After cooling to -78 0C, a 4-phenylbutanal solution (0.74 g, 5.0 mmol) was added. After the mixture was stirred at -78 0C for 3 h, it was warmed to r.t. and a phosphate buffer (pH 7.0, 0.10 M, 150 mL) was added with stirring for an additional 10 min. The mixture was filtered and the solid washed with ether. The aqueous phase was extracted with ether (3 X 50 mL) and the combined organic phase was washed with brine and dried over Na2SO4. Solvent was removed and the residue was purified by silica gel column chromatography (3 X 25 cm, hexanes: EtOAc 9:1) to give compound 65 as a colorless viscous oil (850mg, 49percent). 1H NMR (500 MHz, CDCl3) delta 7.28-7.25 (m, 2 H), 7.19-7.15 (m, 3 H), 3.94 (d, / = 3.5 Hz, 1 H), 3.70 (s, 3 H), 3.64 (s, 3 H), 3.59 (dt, J = 2.0, 10.3 Hz, IH), 2.66-2.60 (m, 2 H), 2.28-2.25 (m, 1 H), 1.99 (d, J = 10.0 Hz, 1 H), 1.95-1.85 (m, I H), 1.75-1.65 (m, I H), 1.60-1.52 (m, 1 H), 1.35 (s, I H), 1.33-1.23 (m, 1 H), 1.08 (d, / = 7.0 Hz, 3 H), 0.69 (d, / = 6.9 Hz, 1 H). ESIMS (MNa+) m/z 369.4.[000200] Compound 65 (692 mg, 2.0 mmol) is dissolved in acetonitrile (24 mL) containing HCl (0.50 M, 24 mL). After the mixture is stirred at r.t. for 12 h, the solvent is removed, the residue is dissolved in a NaOH solution (2.0 M, 20 mL) in MeOH (2OmL), and the progress of the reaction is monitored by TLC. The reaction mixture was neutralized with a solution of HOAc, and solvent is removed. The residue is purified by reverse phase HPLC to give desired product, compound 66, as an amorphous white solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 109838-85-9, its application will become more common.

Reference:
Patent; FORBES MEDI-TECH (RESEARCH), INC.; WO2008/31032; (2008); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem