Author: Jessica.F

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. 6863-74-7, name is 6-Chloropyrazine-2-carbonitrile belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 6863-74-7

A mixture of tert-butyl ((1R,4R,7R)-2-(1-(azetidin-3-ylmethyl)-2-(1- (cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1H-benzo[d]imidazole- 5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (15 mg, 0.024 mmol), 6- chloropyrazine-2-carbonitrile (3.34 mg, 0.024 mmol), cesium carbonate (15.62 mg, 0.048 mmol), BINAP (0.746 mg, 1.199 mmol) and Pd2(dba)3 (1.098 mg, 1.199 mmol) in degassed dioxane (1.0 mL) under nitrogen in a seal vial was stirred at 90C for 18 hour. The mixture was diluted with EtOAc (5 mL) and was washed with a solution of aqueous saturated sodium bicarbonate (5 mL). The organic layer was dried over sodium sulfate and concentrated to give crude tert-butyl ((1R,4R,7R)-2-(1-(azetidin-3-ylmethyl)-2-(1- (cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1H-benzo[d]imidazole- 5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (15 mg, 0.024 mmol). Material was used as is in next reaction.

The synthetic route of 6863-74-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; NGU, Khehyong; (435 pag.)WO2020/33514; (2020); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

1458-16-8, 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. 1458-16-8 name is Methyl 3-amino-6-iodopyrazine-2-carboxylate, 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.

Example 3b: 3-amino-6-iodopyrazine-2-carboxamide 30 ml of ammonia in water is added under magnetic stirring to 15 g (53.8 mmol) of a solution of methyl 3-amino-6-iodopyrazine-2-carboxylate in 150 ml of methanol. The reaction medium is stirred at 25C for 48 hours. After evaporation of the solvents, the precipitate obtained is filtered, rinsed with water and then dried at 50C to yield 12.50 g of 3-amino-6-iodopyrazine-2-carboxamide (88%) in the form of a beige solid. LCMS (EI, m/z): (M+l) 265.02 1H NMR: deltaEta ppm (400 MHz, DMSO): 8.35 (1H, s, CHarom), 7.85 (1H, bs, NH), 7.60 (3H, bs, NH), 3.25 (3H, s, CH3).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-amino-6-iodopyrazine-2-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; PIERRE FABRE MEDICAMENT; KRUCZYNSKI, Anna; CREANCIER, Laurent; KALOUN, El Bachir; BEDJEGUELAL, Karim; RABOT, Remi; WO2014/16434; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 957344-74-0, name is 5,8-Dibromoimidazo[1,2-a]pyrazine, molecular formula is C6H3Br2N3, 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. 957344-74-0

Step 3 4-(5-Bromoimidazo[l,2-a]pyrazin-8-ylamino)-N-(2-diethylaminoethyl) benzene sulfonamide[00262] A mixture of 5,8-dibromoimidazo[l,2-a]pyrazine (1.Og, 3 6mmol), 4-amino-N-(2- diethylaminoethyl)benzenesulfonamide (109mg, 0 4mmol), Pd2(dba)3 (7mg, 0.007mmol), Xantphos(8.4mg, 0.015mmol) and Cs2CO3 (167mg, 0 52mmol) in dioxane is heated at 850C under nitrogen for 18 hours The reaction is cooled to room temperature then evaporated to dryness The residue is chromatographed on silica gel, elutmg with DCM then 98 2 DCM NH3 (7N m MeOH), and the fractions containing the title compound are combined and evaporated to afford a dark oil This oil contains an impurity, but is used in the subsequent step without further purification

The chemical industry reduces the impact on the environment during synthesis 5,8-Dibromoimidazo[1,2-a]pyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; GALAPAGOS N.V.; WO2007/131991; (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. 33332-28-4, name is 2-Amino-6-chloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 33332-28-4

A solution of 82 2-amino-6-chloropyrazine (25 g, 193.1 mmol) in 83 MeOH (500 mL) was treated with 84 NBS (34.3 g, 193.1 mmol), portion-wise, over 1 hour. The resulting mixture was stirred for 16 hours thereafter. TLC analysis at this time shows a small amount of starting material remaining. Another 1.4 g NBS added and reaction heated to 50¡ã C. for 2 hours. The mixture was then cooled to 38¡ã C. and treated with 85 NCS (25.8 g, 193.1 mmol). The reaction mixture was heated to 50¡ã C. for 16 hours thereafter. The mixture was then cooled to room temperature and treated with 39 water (500 mL). The precipitate was collected by filtration and dried in a vacuum desiccator to afford 45.4 g (97percent yield) of 86 2-amino-5-bromo-3,6-dichloropyrazine as a white solid: 13C NMR (75 MHz, CDCl3) ? 149.9 (s), 145.6 (s), 129.6 (s), 121.5 (s). LCMS (15-95percent gradient acetonitrile in 0.1percent TFA over 10 min), single peak retention time=4.51 min on 30 mm column, (M+H)+=244, (M+H+ACN)+=285.

The synthetic route of 33332-28-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MediBeacon Inc.; Debreczeny, Martin P.; Rajagopalan, Raghavan; Dorshow, Richard B.; Neumann, William L.; Rogers, Thomas E.; (54 pag.)US2019/125901; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

87486-34-8, Adding some certain compound to certain chemical reactions, such as: 87486-34-8, name is 3,5-Dibromo-1-methylpyrazin-2(1H)-one, 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 87486-34-8.

A solution of 3,5-dibromo-1-methylpyrazin-2-one (500.0 mg, 2.46 mmol), NH3H2O (5.0 mL) in dioxane (30.0 mL) was heated at 105¡ã C. for 20 h. The mixture was concentrated, diluted with EtOAc (50 mL) and filtrated to give the title compound (300.0 mg, 79.0percent) which was carried on without purification. LCMS (M+H)+ 204.

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 87486-34-8.

Reference:
Patent; Bennett, Michael John; Betancort, Juan Manuel; Boloor, Amogh; Kaldor, Stephen W.; Stafford, Jeffrey Alan; Veal, James Marvin; US2015/111885; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding some certain compound to certain chemical reactions, such as: 33332-31-9, name is 2-Chloro-5-methoxypyrazine, 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 33332-31-9. 33332-31-9

Preparation of tert-butyl 4-((5-methoxypyrazin-2-yl)oxy)piperidine-l- carboxylate. To a solution of tert-butyl 4-hydroxy-4-methylpiperidine-l-carboxylate (278 mg, 1.38 mmol) in DMF (1.7 mL) was added sodium hydride (60% w/w, 61 mg, 1.52 mmol). The reaction was stirred for 5 min at ambient temperature. Then 2-chloro-5-methoxypyrazine (100 mg, 0.692 mmol) was added and reaction stirred overnight at 95C. The reaction was cooled to ambient temperature and diluted with DCM and washed with saturated NaHC03(aq), water, and brine. The combined organic extracts were dried over anhydrous Na2S04(S), filtered and concentrated in vacuo. The residue was purified by silica chromatography (5-40% EtOAc in hexanes as the gradient eluent) to afford the title compound (assumed quantative yield, 214 mg) in sufficient purity for step 2. MS (apci) m/z = 210.1 (M-Boc).

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-5-methoxypyrazine.

Reference:
Patent; ANDREWS, Steven W.; ARONOW, Sean; BLAKE, James F.; BRANDHUBER, Barbara J.; COLLIER, James; COOK, Adam; HAAS, Julia; JIANG, Yutong; KOLAKOWSKI, Gabrielle R.; MCFADDIN, Elizabeth A.; MCKENNEY, Megan L.; MCNULTY, Oren T.; METCALF, Andrew T.; MORENO, David A.; RAMANN, Ginelle A.; TANG, Tony P.; REN, Li; WALLS, Shane M.; (946 pag.)WO2018/71454; (2018); 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 138588-41-7 as follows. 138588-41-7

7-chloro-N,N,9-trimethyl-2-pyrazin-2-yl-9H-pyrimido[4,5-b]indole-4-carboxamide 0.6 g (26 mmol) of sodium was dissolved under nitrogen in 150 ml of absolute ethanol. Next, 1.2 g (7.6 mmol) of pyrazine-2-carboxamidine hydrochloride was added. After stirring for 1 h 30 min, the residual insoluble part was isolated by filtration and the filtrate was concentrated under reduced pressure. 150 ml of dichloromethane was added and the mixture was filtered. The filtrate was concentrated under reduced pressure. Added to the residue were 100 ml of xylene, then 0.24 g (0.80 mmol) of 2-(2,6-dichloro-1-methyl-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide, obtained according to step 1.2. from example 1. The mixture was heated under reflux for 18 h. It was then cooled and concentrated under reduced pressure. Dichloromethane, water and a (1M) aqueous solution of sodium hydroxide was added. The organic phase was decanted, washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column with a mixture of solvents (dichloromethane/ethyl acetate: 80/20 to 0/100, then ethyl acetate/methanol: 100/0 to 95/5). The compound obtained was recrystallized in an ethyl acetate/methanol mixture, it was isolated by filtration, rinsed with diethyl ether and dried under reduced pressure. 0.070 g of 7-chloro-N,N,9-trimethyl-2-pyrazin-2-yl-9H-pyrimido[4,5-b]indole-4-carboxamide was isolated in the form of a white solid. M.P.: 272-273 C. LC/MS: M+H=367 1H NMR (CDCl3, 200 MHz): 9.9 (s, 1H); 8.9 (d, 1H); 8.7 (d, 1H); 8.1 (d, 1H); 7.6 (d, 1H); 7.4 (dd, 1H); 4.1 (s, 3H); 3.4 (s, 3H); 3.1 (s, 3H).

According to the analysis of related databases, 138588-41-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SANOFI-AVENTIS; US2008/125410; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

2423-65-6, These common heterocyclic compound, 2423-65-6, name is Pyrazine 1-oxide, 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.

General Procedure 2:; Palladium-Catalyzed Direct Arylation with Aryl Chlorides and Bromides.; To a dried flask was added the diazine N-oxide (1.0 to 3.0 equiv.), K2CO3 (2.0 equiv.), Pd(OAc)2 (5 mol %) and HP(t-Bu)3BF4 (15 mol %). If the arylhalide is a solid, it is added at this point (1.0 equiv.). The flask and its contents were then purged under nitrogen for 10 minutes. If the aryl halide is a liquid, it is added via syringe after purging, followed by the addition of degassed dioxane (to produce a reaction concentration of 0.3 M relative to the halide). The reaction mixture was then heated at 110 C. until the reaction was complete, after which the volatiles were removed under reduced pressure and the residue was purified via silica gel column chromatography.2-Styrylpyrazine N-oxide (Table 4, Entry 12) Synthesised according to general procedure 2. Purification via silica gel column chromatography using 100% DCM, then a mixture of 10% Acetone/DCM gave a brownish solid, 32% yield with 2 eq. of the N-oxide and 40% yield with 3 eq. of the N-oxide). 1H NMR (300 MHz, CDCl3, 293K, TMS): delta 8.82 (1H, s), 8.31-8.22 (1H, m), 8.14-8.11 (1H, m), 7.72 (1H, d, J=16.5 Hz), 7.62 (2H, dd, J=3.0 and 7.8 Hz), 7.53 (1H, d, J=16.5 Hz), 7.45-7.34 (3H, m) 13C NMR (75 MHz, CDCl3, 293K, TMS): 145.8, 143.9, 136.7, 135.7, 133.9, 129.5, 128.9, 128.4, 127.5, 115.6.

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 2423-65-6.

Reference:
Patent; University of Ottawa; US2008/132698; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

109-08-0, name is 2-Methylpyrazine, 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. 109-08-0

Compound 16: (E)-2-[2-(Pyridin-2-yl)vinyl]pyrazine hydrochloride: s-Butyl lithium (2.5 M in hexanes, 4.8 mL, 12.0 mmol, 1.2 eq.) was added dropwise to a solution of diisopropylamine (1.83 mL, 1.32 g, 13.0 mmol, 1.3 eq.) in dry tetrahydrofuran (25 mL) at -78 ¡ãC. The mixture was stirred at -78 ¡ãC for 10 min and 2-methylpyrazine (0.91 mL, 0.94 g, 10.0 mmol, 1.0 eq.) was added dropwise. The resulting mixture was stirred at -78 ¡ãC for a further 30 min. 2-Pyridinecarboxaldehyde (0.96 mL, 1.07 g, 10.0 mmol, 1.0 eq.) was added dropwise and the mixture was allowed to slowly warm up to room temperature over 1 h while stirring. The reaction was quenched by addition of water (10 mL). The pH was adjusted to -10 by careful addition of cone. HCl and then the mixture was extracted with dichloromethane (2 x 25 mL). The combined organic extracts were washed with brine (25 mL), dried over sodium sulfate and evaporated in vacuo. The crude product was purified by column chromatography (Si02, 1:9 methanol-ethyl acetate) to provide 2-(pyrazin-2-yl)-1-(pyridin-2-yl)ethanol (1.08 g, 54percent yield) as a clear yellow oil. p-Toluenesulfonyl chloride (1.12 g, 5.9 mmol, 1.1 eq.) was added to a stirred solution of 2- (pyrazin-2-yl)-1-(pyridin-2-yl)ethanol (1.08 g, 5.4 mmol, 1.0 eq.) and triethylamine (2.24 mL, 1.63 g, 16.1 mmol, 3.0 eq.) in dichloromethane (25 mL). The mixture was stirred at room temperature for 23 h. The mixture was washed with aqueous NaOH (15percent, 25 mL), water (25 mL) and brine (25 mL). The organic layer was dried over sodium sulfate and evaporated in vacuo. The crude product was purified by column chromatography (Si02, 1:9 methanol-ethyl acetate) providing a mixture of 2-(pyrazin-2-yl)-1-(pyridin-2-yl)ethyl 4-methylbenzenesulfonate and (E)-2-(2-(pyridin-2-yl)vinyl)pyrazine (0.54 g). l,8-Diazabicyclo[5.4.0]undec-7-ene (0.45 mL, 0.46 g, 3.0 mmol, 2.0 eq.) was added dropwise to a stirred solution of 2-(pyrazin-2-yl)-1-(pyridin-2-yl)ethyl 4-methylbenzenesulfonate (0.54 g, 1.5 mmol, 1.0 eq.) in dichloromethane (10 mL). The mixture was stirred at room temperature for 4 h. The mixture was evaporated in vacuo and the crude product was purified by column chromatography (SiO2, ethyl acetate) providing (E)-2-(2-(pyridin-2-yl)vinyl)pyrazine (0.50 g, 100percent) as a white solid. A solution of hydrochloric acid (2.0 M in diethyl ether, 0.65 mL, 1.3 mmol, 1.2 eq.) was added dropwise to a stirred suspension of (E)-2-(2-(pyridin-2-yl)vinyl)pyrazine (0.20 g, 1.1 mmol, 1.0 eq.) in dry diethyl ether (7.5 mL). The mixture was stirred at room temperature for 1 h and then the solids removed by filtration. The product was washed with diethyl ether (3 x 10 mL) and then dried in vacuo to provide (E)-2-[2-(pyridin-2-yl)vinyl]pyrazine hydrochloride (0.21 g, 83percent yield) as a fine white solid; 1H NMR (400 MHz, DMSO-d6) delta 7.78 (t, J = 7.0 Hz, 1H, Ar), 7.99 (d, J = 16.0 Hz, 1H, C=CH), 8.11 (d, J = 16.0 Hz, 1H, C=CH), 8.25 (d, J = 8.0 Hz, 1H, Ar), 8.38 (t, J = 8.0 Hz, 1H, Ar), 8.65 (d, J = 2.5 Hz, 1H, Ar), 8.75 (t, J = 2.0 Hz, 1H, Ar), 8.79 (d, J = 5.0 Hz, 1H, Ar), 8.88 (d, J = 2.0 Hz, 1H, Ar).

Statistics shows that 109-08-0 is playing an increasingly important role. we look forward to future research findings about 2-Methylpyrazine.

Reference:
Patent; UNIVERSITY COLLEGE DUBLIN – NATIONAL UNIVERSITY OF IRELAND, DUBLIN; THE PROVOST, FELLOWS, FOUNDATION SCHOLARS, AND THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY AND UNDIVIDED TRINITY OF QUEEN ELIZABETH, NEAR DUBLIN; KENNEDY, Breandan; REYNOLDS, Alison; O’SULLIVAN, Jacintha; BAXTER, Andrew, Douglas; WO2015/107122; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem