Month: December 2020

767340-03-4, name is (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine, belongs to Pyrazines compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. 767340-03-4

Into a 500 ml flask were charged chloro(l,5-cyclooctadiene)rhodium(I) dimer {[Rh(cod)Cl]2}(292 mg, 1.18 mmol) and (R,S) f-butyl Josiphos (708 mg, 1.3 mmol) under a nitrogen atmosphere. Degassed MeOH was then added (200 mL) and the mixture was stirred at room temperature for 1 h. Into a 4 L hydrogenator was charged the enamine amide 2Lambda (118 g, 0.29 mol) along with MeOH (1 L). The slurry was degassed. The catalyst solution was then transferred to the hydrogenator under nitrogen. After degassing three times, the enamine amide was hydrogenated under 200 psi hydrogen gas at 50 0C for 13 h. Assay yield was determined by EtaPLC to be 93% and optical purity to be 94% ee.The optical purity was further enhanced in the following manner. The methanol solution from the hydrogenation reaction (18 g in 180 mL MeOH) was concentrated and switched to methyl t- butyl ether (MTBE) (45 mL). Into this solution was added aqueous Eta3PO4 solution (0.5 M, 95 mL).After separation of the layers, 3NNaOH (35 mL) was added to the water layer, which was then extracted with MTBE (180 mL + 100 mL). The MTBE solution was concentrated and solvent switched to hot toluene (180 mL, about 75 0C). The hot toluene solution was then allowed to cool to 0 0C slowly (5 – 10 h). The crystals were isolated by filtration (13 g, yield 72%, 98 – 99% ee); m.p. 114.1 – 115.7 0C. lH NMR (300 MHz, CD3CN): delta 7.26 (m), 7.08 (m), 4.90 (s), 4.89 (s), 4.14 (m), 3.95 (m), 3.40 (m), 2.68(m), 2.49 (m), 1.40 (bs).Compound 2-5 exists as amide bond rotamers. Unless indicated, the major and minor rotamers are grouped together since the carbon-13 signals are not well resolved: 13c NMR (CD3CN): delta 171.8, 157.4 (ddd , JCF = 242.4, 9.2, 2.5 Hz), 152.2 (major), 151.8 (minor), 149.3(ddd; JCF = 246.7, 14.2, 12.9 Hz), 147.4 (ddd, JCF = 241.2, 12.3, 3.7 Hz), 144.2 (q, JCF = 38.8 Hz), 124.6 (ddd , JCF = 18.5, 5.9, 4.0 Hz), 120.4 (dd , JCF = 19.1, 6.2 Hz), 119.8 (q, JCF = 268.9 Hz), 106.2 (dd , JCF = 29.5, 20.9 Hz), 50.1, 44.8, 44.3 (minor), 43.2 (minor), 42.4, 41.6 (minor), 41.4, 39.6, 38.5 (minor), 36.9. The crystalline free base 2^ can also be isolated as follows:(a) The reaction mixture upon completion of the hydrogenation step is charged with 25 wt% of Ecosorb C-941. The mixture is stirred under nitrogen for one h and then filtered. The cake is washed with 2L/kg of methanol. Recovery of free base is about 95% and optical purity about 95% ee.(b) The freebase solution in methanol is concentrated to 3.5-4.0 L/kg volume (based on free base charge) and then solvent-switched into isopropanol (IPA) to final volume of 3.0 L/kg IPA.(c) The slurry is heated to 40 0C and aged 1 h at 4O0C and then cooled to 25 0C over 2 h. EPO (d) Heptane (7L/kg) is charged over 7 h and the slurry stirred for 12 h at 22-250C. The supernatant concentration before filtering is 10-12 mg/g.(e) The slurry is filtered and the solid washed with 30% IPA/heptane (2L/kg).(f) The solid is dried in a vacuum oven at 40 0C. (g) The optical purity of the free base is about 99% ee.

Statistics shows that 767340-03-4 is playing an increasingly important role. we look forward to future research findings about (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine.

Reference:
Patent; MERCK & CO., INC.; WO2006/33848; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

1458-18-0, A common compound: 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, belongs to Pyrazines compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

S-Amino–chloro-S-methoxy-pyrazine-?-carboxylic acid methyl ester [00442]Methyl 3-amino-5,6-dichloropytauazinoate (1.1 g, 5 mmol) was dissolved in 200 mL of boiling anhydrous methanol containing metallic sodium (115 mg, 5 mmol). The product which separates on cooling, is filtered, washed with water and methanol and dried to give 1.Og (92%) of methyl S-amino-S-methoxy–chloro-pyrazinoate which was recrystallized from acetonitrile. MP. 255-257 C. [00443J 1H NMR (DMSO-rf?, 400MHz): delta 7.61 Qm, 2H, NH2, exchangeable with D2O), 3.97 (s, 3H), 3.80 (s, 3H).

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, Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ARDEA BIOSCIENCES INC.; WO2009/89263; (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. 5521-58-4, name is 5-Methylpyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., 5521-58-4

[0386] A mixture of 5-methylpyrazine-2-carboxylic acid (2.76 g, 20 mmol) and oxalyl chloride (1.83 mL, 2.66 g, 21 mmol) in methylene chloride (40 mL) was treated with N,N-dimethylformamide (0.5 mL), and the mixture was stirred at 25 C. for 1 h. The mixture was filtered, and the filtrate was concentrated in vacuo to give an oily solid. The solid was dissolved in acetone (120 mL) at 0 C. and then sodium azide (1.03g, 20 mmol) in water (50 mL) was added dropwise. After the addition was complete, stirring was continued at 0 C. for 30 min. The mixture was then poured into ice cold water (100 mL) and extracted with methylene chloride (3¡Á100 mL). The combined organic extracts were washed with water (1¡Á100 mL), a mixture of a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution (1:1, 1¡Á100 mL), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated in vacuo to give 5-methyl-pyrazine-2-carbonyl azide (1.46 g, 45%) as a tan solid. The 5-methyl-pyrazine-2-carbonyl azide (500 mg, 3.07 mmol) was combined with benzyl alcohol (0.63 mL, 663 mg, 6.14 mmol) at 25 C. The mixture was then slowly heated on an oil bath to 90 C., upon which gas was violently evolved. The oil bath temperature was maintained until gas evolution ceased. The oil bath temperature was raised to 120 C. and stirring was continued for 10 min at that temperature. The mixture was cooled and triturated with diethyl ether/hexanes (1:4) to give (5-methylpyrazin-2-yl)-carbamic acid phenyl ester (438 mg, 58%) as a yellow solid. The (5-methylpyrazin-2-yl)-carbamic acid phenyl ester (500 mg, 2.2 mmol) and 10% palladium on carbon (212 mg) were mixed in ethanol (30 mL). The reaction vessel was flushed with hydrogen, and the mixture was stirred at 25 C. for 1 h under hydrogen (1 atm). The excess hydrogen was evacuated from the reaction vessel, and the mixture was filtered through a pad of celite. Concentration of the filtrate in vacuo gave 2-amino-5-methylpyrazine (183 mg, 76%) as a tan solid which was used without further purification. [0387] A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-oxo-cyclohexyl)-propionic acid (prepared as in Example 60, 263 mg, 0.73 mmol) and triphenylphosphine (250 mg, 0.95 mmol) in methylene chloride (5.0 mL) cooled to 0 C. was treated with N-bromosuccinimide (167 mg, 0.95 mmol) in small portions. After the complete addition of N-bromosuccinimide, the reaction mixture was allowed to warm to 25 C. over 30 min. The bright orange reaction mixture was then treated with 2-amino-5-methylpyrazine (160 mg, 1.46 mmol) and 2,6-lutidine (0.36 mL, 2.92 mmol). The resulting reaction mixture was stirred at 25 C. for 4 h. The reaction mixture was then diluted with methylene chloride (25 mL) and was successively washed with a 10% aqueous hydrochloric acid solution (1¡Á20 mL), a saturated aqueous sodium bicarbonate solution (1¡Á20 mL) and water (1¡Á20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 65/35 hexanes/ethyl acetate to 3/7 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-methyl-pyrazin-2-yl)-3-(4-oxo-cyclohexyl)-propionamide (158 mg, 48%) as a white foam: [alpha]23589=-41.52 (c=0.33, chloroform); EI-HRMS m/e calcd for C20H21Cl2N3O4S (M+H)+ 450.1249, found 450.1253.

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; Corbett, Wendy Lea; Grimsby, Joseph Samuel; Haynes, Nancy-Ellen; Kester, Robert Francis; Mahaney, Paige Erin; Racha, Jagdish Kumar; Sarabu, Ramakanth; Wang, Ka; US2003/225283; (2003); 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. 3149-28-8, name is 2-Methoxypyrazine, A new synthetic method of this compound is introduced below., 3149-28-8

First, in a three-neck flask, 11.30 g of 2-methoxypyrazine and 200 mL of diethylether were put, and a dibutyl ether solution (2.1 mol/L) of phenyl lithium was dropped thereto while the mixture was cooled down with ices and stirred under a nitrogen atmosphere, and stirred to be reacted for 20 hours. After the reaction, water was added to the reaction solution, and an organic layer was extracted with ethyl acetate. The obtained organic layer was washed with water, and dried with magnesium sulfate. Magnesium sulfate was removed by filtration and the solvent was distilled off. The obtained residue was refined with a column chromatography using dichloromethane as a development solvent, so that 2-phenyl-3-methoxypyrazine was obtained (light yellow powder, yield: 12%).

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; Semiconductor Energy Labratory Co., Ltd.; US2008/312437; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

5521-58-4, Name is 5-Methylpyrazin-2-amine, 5521-58-4, belongs to Pyrazines compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows.

To a clean dry flask was added 3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid (1.0 mol eq), tetrabutylammonium chloride (0.01 eq), and toluene (10 L/kg). Thionyl chloride (1.5 eq) was added in one go and the reaction heated to 60 C. for 2 hours. The reaction mixture was distilled to an oil at 40 C. on the rotary evaporator, and acetonitrile (4 L/kg) added.To a second clean dry flask was added 5-methylpyrazine-2-amine (1.0 mol eq), pyridine (3.0 mol eq) and acetonitrile (4 L/kg). The acid chloride solution was added to the amine solution over 30 minutes at 22 C. and then allowed to agitate overnight.The reaction mixture was distilled to an oil at 40 C. on the rotary evaporator, and toluene (4 L/kg) added. The reaction mixture was distilled to give an oil at 40 C. on the rotary evaporator, then toluene (10 L/kg added) followed by water (4 L/kg) and 1.0M hydrochloric acid (4 L/kg). The reaction mixture was agitated at 22 C. for 30 minutes, whereupon it crystallized, and toluene (4 L/kg) and water (4 L/kg) was added.The reaction mixture was filtered and washed sequentially with water 2¡Á(2 L/kg), then toluene 2¡Á(2 L/kg).The filtrate was agitated overnight at 22 C. and further crystallisation was observed. The reaction mixture was filtered. The solids were dried to give the title compound as an off-white solid in 35% yield.1H NMR delta (400 MHz DMSO) 10.86 (bs, 1H), 9.75 (bs, 1H), 9.25-9.24 (s, 1H), 9.35 (s, 1H), 6.99 (t, 1H), 6.81 (t, 1H), 6.53-6.52 (t, 1H), 4.72-4.65 (m, 1H), 3.52-3.43 (m, 2H), 3.30 (s, 3H), 2.48 (s, 3H), 1.24-1.22 (d, 3H).

Statistics shows that 5-Methylpyrazin-2-amine is playing an increasingly important role. we look forward to future research findings about 5521-58-4.

Reference:
Patent; AstraZeneca AB; US2010/210841; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

20737-42-2, 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. 20737-42-2, name is 3-Oxo-3,4-dihydropyrazine-2-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows.

Example 6. Production of N-{3-isobutyl-4-[2,2,2-trifluoro-1-(trifluoromethyl)ethyl]pheny}-3-chloropyrazine-2-carboxamide (compound No. 1-25) 3-Hydroxypyrazine-2-carboxylic acid (154 mg, 1.1 mmol) was dissolved in phosphorus oxychloride (2 ml), followed by adding one drop of pyridine, refluxing under heating for 2 hours. After that, the reaction solution was concentrated under reduced pressure to obtain 3-chloropyrazine-2-carboxylic acid chloride. The compound was added to a tetrahydrofuran solution (10 ml) of 3-isobutyl-4-[2,2,2-trifluoro-1-(trifluoromethyl)ethyl]aniline (299 mg, 1 mmol) and triethylamine (303 mg, 3 mmol) and refluxed under heating for 3 hours. The reaction solution was diluted with ethyl acetate, followed by washing with water. The organic layer was dried over magnesium sulfate anhydride, and concentrated under reduced pressure, and then the residue was purified by using silica gel chromatography (hexane:ethyl acetate=2:1) to obtain 200 mg of the desired compound. Yield: 46% Property: Melting point 128 to 129C

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; NIHON NOHYAKU CO., LTD.; EP1757595; (2007); 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. 24241-18-7, name is 2-Amino-3,5-dibromopyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 24241-18-7

To a solution of 3,5-dibromopyrazin-2-amine (40.0 g, 158 mmol), TEA (66.1 mL, 475 mmol), and copper(I) iodide (0.301 g, 1.58 mmol) in THF (1172 ml) was added PdCl2(PPh3)2 (1.11 g, 1.58 mmol). The reaction mixture was cooled at about 0 C. and a solution of (trimethylsilyl)acetylene (20.8 mL, 150 mmol) in THF (146 mL) was added drop-wise. The reaction mixture was stirred at about 0-10 C. for about 7 h and then concentrated under reduced pressure. The dark brown residue was dissolved in DCM (600 mL) and filtered through a Celite pad (3 cm in height¡Á9 cm in diameter) while eluting with DCM (300 mL). The filtrate was washed with water (2¡Á500 mL) and brine (500 mL), dried over anhydrous MgSO4, filtered through a Florisil pad (1 cm in height by 9 cm in diameter) while washing with DCM/MeOH (9:1, 200 mL), and concentrated under reduced pressure to give a brown solid. The solid was triturated and sonicated with warm petroleum ether (b.p. 30-60 C., 250 mL), cooled and collected, washing with petroleum ether (b.p. 30-60 C.; 2¡Á100 mL), and dried in a vacuum oven at about 70 C. to give 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (34.6 g, 70%): LC/MS (Table 2, Method d) Rt=1.59 min; MS m/z: 272 (M+H)+.

The synthetic route of 24241-18-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ABBOTT LABORATORIES; US2009/312338; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding some certain compound to certain chemical reactions, such as: 95-58-9, name is 2-Chloro-3-methylpyrazine, 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 95-58-9. 95-58-9

Compound 1 (500 g, 1.92 mol) and aqueous ammonia (5.5 L) were placed in a 10 L autoclave and reacted at 160 C for 24 hours. TLC or LCMS showed the reaction was completed.The reaction was cooled and filtered to give a white solid, the remaining reaction solution was extracted with ethyl acetate (1.5 L x 5), the extracts were combined, dried over anhydrous sodium sulfate,The resulting white solid was concentrated under reduced pressure and combined with the filtered solid which was dried in vacuo to give crude compound 2 (420 g).

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 2-Chloro-3-methylpyrazine.

Reference:
Patent; Shanghai He Quan Pharmaceutical Co., Ltd.; Shanghai He Quan Pharmaceutical Research And Development Co., Ltd.; Changzhou Hequan Pharmaceutical Co., Ltd.; Changzhou Hequan Drug Discovery Co., Ltd.; Wuxi Yaoming Kant, Immanuel Pharmaceutical Co., Ltd.; Wuxi Yaoming Kant, Immanuel Bio-technology Co., Ltd.; Mao Yanjun; Tang Xiaowu; Guo Zemin; He Mina; Jiang Xinxin; Bao Weize; Wu Dongping; Yuan Chaowei; Li Hong; Yu Lingbo; Ma Rujian; (5 pag.)CN107312007; (2017); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 5049-61-6 name is Pyrazin-2-amine, 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. 5049-61-6

Preparation c-119 5-Bromo-pyrazin-2-ylamine To a solution of pyrazin-2-ylamine (2.0 g, 21.03 mmol) in dry dichloromethane (120 mL) at 0 C., was added N-bromosuccinimide (3.74 g, 21.03 mmol) slowly to maintain the internal temperature below 0 C. The mixture was stirred at the same temperature for 24 hours, and then washed with saturated aqueous sodium bicarbonate (30 mL) and water (30 mL). The combined aqueous extracts were extracted with dichloromethane (3*100 mL). The combined organic extracts were. dried (anhydrous magnesium sulfate), filtered, and concentrated in vacuo to afford the crude product. The residue was purified by flash column chromatography (10% to 50% ethyl acetate/hexanes) to yield the title compound (2.57 g, 70%) as a yellow solid. LRMS (m/z): 174 (M)-. 1H NMR (CDCl3, 300 MHz): delta 8.08 (1H, d, J=1,3 Hz), 7.76 (1H, d, J=1,3 Hz).

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

Reference:
Patent; Pfizer Inc; US2005/187266; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding some certain compound to certain chemical reactions, such as: 486460-21-3, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, 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 486460-21-3. 486460-21-3

((c/s-1-(3-Chlorophenyl)-4-f3-(trifluoromethyl)-5.6-dihvdrori.2.4ltriazolof4.3-a1pyrazin- 7(8H)-yl1cvclohexyl)methyl)-carbamic acid tert-butyl ester and ((^ra/7s-1-(3-chlorophenyl)-4- f3-(triflupsilonoromethyl)-5.6-dihvdrof1.2.41triazolof4.3-a1pyrazin-7(8H)-vncvclohexyl>methyl)- carbamic acid tert-butyl esterSodium triacetoxyborohydride (316mg, 1.49mmol) was added to a solution of [1-(3- chlorophenyl)-4-oxo-cyclohexylmethyl]-carbamic acid tert-butyl ester (360mg, 1.07mmol) and 3-trifluoromethyl-5,6,7,8-tetrahydro-[1 ,2,4]triazolo[4,3-a]pyrazine (286.4mg, 1.49mmol) in 1 ,2-dichloroethane and the mixture was stirred at room temperature for 24h. The reaction was quenched with water and the product was extracted with ethyl acetate. The organic extracts were washed with brine, dried and concentrated in vacuo to give a yellow oil. The oil was purified by flash chromatography (silica, eluting with 1 :33:66 2M ammonia in methanol:ethyl acetatexyclohexane) to afford the individual title compounds as white solids.Cis diastereoisomer:MS (ES+): 514[M+H]+.TR [HPLC, Phenomenex Luna 3 micron C18; 5-95% CH3CN+0.1%Formic acid/H2O+0.1%Formic acid for 5 min, flow 2.0 ml/min]: 3.70 min.Trans diastereoisomer:MS (ES+): 514[M+H]TR [HPLC, Phenomenex Luna 3 micron C18; 5-95% CH3CN+0.1%Formic acid/H2O+0.1%Formic acid for 5 min, flow 2.0 ml/min]: 3.57min

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 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine.

Reference:
Patent; NOVARTIS AG; WO2008/77597; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem