Author: Jessica.F

Synthetic Route of 76537-18-3, 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 76537-18-3 as follows.

A mixture of 3-bromo-5-chloropyrazin-2-amine (545 mg, 2.61 mmol, D-L Chiral Chemicals) and [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) dichloride (178 mg, 0.261 mmol) in DMA (18.2 mL) was degassed. Separately, a vial was charged with zinc (freshly activated and dried according to the procedure found in WO2011/143365, 1.49 g, 22.8 mmol) and the vial was flushed with N2 and heated with a heat gun, then cooled. Dry THF (20 mL) was added. 1,2-Dibromoethane (0.20 mL, 2.4 mmol) was added and the mixture was heated with a heat gun to reflux, and then cooled to room temperature. This heating and cooling cycle was performed three times. TMSCl (0.60 mL, 4.7 mmol) was added. The mixture was heated to 50 C. in an oil bath, and ethyl 3-iodocyclobutane-1-carboxylate (2.0 g, 7.9 mmol, prepared as described in WO2014/200882, the disclosure of which is incorporated herein by reference in its entirety) in THF (10 mL) was added dropwise. The mixture was maintained at 50 C. for about 1 hour, then was cooled to room temperature and degassed by bubbling a stream of nitrogen through the mixture for 5 min. This mixture was then added to the solution of 3-bromo-5-chloropyrazin-2-amine above, excluding zinc solids. The reaction was heated to 50 C. for 1.75 hours, then to 80 C. for 45 minutes. Upon cooling to room temperature, the reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted again with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The product was purified via flash chromatography, eluting with a gradient from 0-75% EtOAc in hexanes to afford product (0.35 g, 52%). The cis- and trans-isomers are partially separable, however the product was carried as a mixture to the following step. LCMS calculated for C11H15ClN3O2(M+H)+: m/z=256.1, found: 256.0. First diastereomer to elute: 1H NMR (400 MHz, CDCl3) delta 7.97-7.73 (s, 1H), 4.64-4.32 (s, 2H), 4.29-4.14 (q, J=7.1 Hz, 2H), 3.72-3.52 (m, 1H), 3.27-3.10 (m, 1H), 2.80-2.51 (m, 4H), 1.35-1.25 (t, J=7.1 Hz, 3H). Second diastereomer to elute: 1H NMR (400 MHz, CDCl3) delta 7.98-7.78 (s, 1H), 4.59-4.45 (s, 2H), 4.21-4.12 (q, J=7.1 Hz, 2H), 3.47-3.35 (p, J=8.8 Hz, 1H), 3.26-3.15 (m, 1H), 2.77-2.57 (m, 4H), 1.31-1.25 (t, J=7.2 Hz, 3H).

According to the analysis of related databases, 76537-18-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Incyte Corporation; Shepard, Stacey; Combs, Andrew P.; Falahatpisheh, Nikoo; Shao, Lixin; (96 pag.)US2019/276435; (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. 957230-70-5, name is 3,6-Dibromopyrazin-2-amine, A new synthetic method of this compound is introduced below., Quality Control of 3,6-Dibromopyrazin-2-amine

Step 2 5 ,8-Diotabromo-3-methyliotamiotadazo[ 1 ,2 ajpyrazine[00298] 2,5-Dibromo-3-aminopyrazme (2 0 g, 7 9 mmol), 2-bromo-l,l -dimethoxypropane (7 25 g, 40 0 mmol) and py?dimum p-toluenesulfonate (2 0 g, 7 9 mmol) are stirred in acetomtrile (65 mL) at reflux for 3 days The mixture is cooled and the solvent evaporated under reduced pressure The residue is partitioned between DCM (150 mL) and water (50 mL) and the layers separated The organic fraction is washed with NaHCtheta3 (sat aq , 50 mL) and b?ne (50 mL) and d?ed over MgStheta4 Evaporation of the solvent under reduced pressure gives a viscous black oil (2 14 g) which is purified by silica chromatography, elutmg with 10% – 20% EtOAc in cyclohexane to afford the title compound as a red-brown solid (280 mg, 1 mmol)

The synthetic route of 957230-70-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GALAPAGOS N.V.; WO2007/131991; (2007); 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. 5049-61-6, name is Pyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., category: Pyrazines

A compound (1), (2.0 g, 21.0 mmol and 1.0 eq.), and THF (25 ml) were put in and stirred to the 200 ml three necked flask under a nitrogen atmosphere. Next, what dissolved N-bromosuccinimide (8.2 g, 46.1 mmol, 2.2 eq.) in THF (25 ml) was dropped by 0 C, and it agitated for 20 minutes at the room temperature.Cerite filtration of the impurity was carried out after ending reaction. And washed the filtrate by extraction, H2O, and sat.NH4Cl aq. with ethyl acetate, and it was made to dry by Na2SO4, and condensed. a part of obtained residue silica gel column chromatography (7 : n-hexane: eluate : ethyl acetate = 3) separation refinement condensing object compound (2) (3.16 g, yield:60 %) It obtained as a white solid.

According to the analysis of related databases, 5049-61-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; KEIO UNIVERSITY; SUZUKI, KOJI; CITTERIO, DANIEL; KAKUDATE, YOSHIKI; HOSHINO, EMI; NISHIHARA, RYO; (21 pag.)JP2016/50296; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 88625-24-5, name is 5-Chloropyrazine-2-carbaldehyde, 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 88625-24-5, Product Details of 88625-24-5

A solution of 5-chloropyrazine-2-carbaldehyde (5.20 g, 36.5 mmol) in 50 mL of methanol was cooled to O0C. Sodium borohydride (1.45 g, 38.3 mmol) was added and the reaction mixture was allowed to stir at ambient temperature for 3 hour. Saturated aqueous ammonium chloride (5 mL) was added, and the methanol was removed in vacuo. The resulting residue was dissolved in ethyl acetate (50 mL) and washed with aqueous sodium bicarbonate (2 x 50 mL) and brine (50 mL). The combined organic extracts were dried, filtered and concentrated in vacuo to provide the title compound that gave a proton NMR spectra consistent with theory.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Chloropyrazine-2-carbaldehyde, and friends who are interested can also refer to it.

Reference:
Patent; MERCK & CO., INC.; WO2009/134668; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 58138-79-7, name is 2,6-Diiodopyrazine, 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 58138-79-7, Quality Control of 2,6-Diiodopyrazine

A solution of1 (0.10 g, 0.16mmol), 2,6-diiodopyrazine (25 mg, 0.08mmol)and Pd(PPh3)4 (1.5 mg, 1.3 mol) in 1.3ml of toluene wasstirred at 110 C for 10 h. The resulting residue was dissolvedin dichloromethane and washed with water three times. Theorganic layer was concentrated and the residue was purified bychromatography on silica (dichloromethane-hexane = 3:1 aseluent) to give 2,6-PD (58 mg, 72%) as a yellow solid; mp. 273275C; IR(ATR) ~ = 1595, 1493, 1449 cm1; 1HNMR (400MHz, CD2Cl2) = 0.89 (t, J = 7.4 Hz, 6H), 1.291.35(m, 4H),1.761.83(m, 4H), 4.23 (t, J = 7.2 Hz, 4H), 6.96 (dd, J =1.6 and 8.4 Hz, 2H), 7.027.06(m, 4H), 7.147.16(m, 10H),7.257.30(m,8H), 7.53 (d, J = 3.8 Hz, 2H), 7.60 (dd, J = 1.5and 8.1 Hz, 2H), 7.71 (d, J = 1.2 Hz, 2H), 7.79 (d, J = 3.8 Hz,2H), 7.95 (d, J = 8.4 Hz, 2H), 8.03 (d, J = 8.4 Hz, 2H), 8.81(s, 2H) ppm; 13CNMR (100 MHz, CD2Cl2); = 14.06, 20.86,31.46, 43.07, 105.32, 106.28, 117.54, 117.82, 118.64, 120.49,121.27, 123.01, 123.45, 124.43, 124.51, 127.57, 129.57,131.03, 137.88, 140.28, 141,65, 142.85, 147.10, 147.72,148.60, 149.68 ppm; HRMS (APCI): m/z (%): [M + H+] calcdfor C68H57N6S2, 1021.40806; found 1021.40930. (The meltingpoint of 2,6-PD is higher than that of our previous work(ref. 26) because of the improvement of the purification bychromatography.)

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

Reference:
Article; Enoki, Toshiaki; Ohshita, Joji; Ooyama, Yousuke; Bulletin of the Chemical Society of Japan; vol. 91; 12; (2018); p. 1704 – 1709;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

17231-51-5, name is 3-Amino-6-bromopyrazine-2-carbonitrile, 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. COA of Formula: C5H3BrN4

Step 2 : (EJ-S-amino–bromo-TV-hydroxypyrazine-l-carboximidamide[00568] 3-amino-6-bromo-pyrazine-2-carbonitrile (4.5958 g, 23.09 mmol) was dissolved in MeOH (91.92 niL), cooled to 00C and treated with hydroxylamine hydrochloride (1.605 g, 23.09 mmol) and triethylamine (2.336 g, 3.218 mL, 23.09 mmol). The reaction was allowed to warm to ambient temperature, stirred for 48 hours and then evaporated to dryness. Methanol (a minimum amount) was added, the mixture sonicated, filtered and washed with MeOH to give the product as a brown solid 5.27 g, 98% Yield). IH NMR (400.0 MHz, DMSO) d 5.88 (s, 2H), 7.64 (br s, 2H), 8.14 (s, IH) and 10.38 (s, IH) ppm; MS (ES+) 233.75

The synthetic route of 17231-51-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-damien; DURRANT, Steven; KAY, David; O’DONNELL, Michael; KNEGTEL, Ronald; MACCORMICK, Somhairle; PINDER, Joanne; VIRANI, Anisa; YOUNG, Stephen; BINCH, Hayley; CLEVELAND, Thomas; FANNING, Lev, T.d.; HURLEY, Dennis; JOSHI, Pramod; SHETH, Urvi; SILINA, Alina; WO2010/54398; (2010); 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. 762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, A new synthetic method of this compound is introduced below., Quality Control of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride

(3R)-3-te/-t-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyric acid (40 g, 0.12 mol) was dissolved in dimethylformamide (DMF)(240 mL) at room temperature while the reaction flask was under N2, then, cooled with ice bath and stirred for 30 minutes. In a different flask, DCC (32.21 g, 0.16 mol) was dissolved in DMF (160 mL) to obtain a 200 mL solution. To the (3R)-3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro- phenyl)-butanoic acid solution was added 70 mL from the DCC solution drop-wise, 3- (trifluoromethyl)-5,6,7,8-tetrahydro-[l,2,4]triazolo[4,3-a]pyrazine hydrochloride (32.94 g, 0.14 mol) and Et3N (24.82 g, 0.24 mol). The reaction was stirred for 10 minutes, then, DMAP was added (8.8 g, 0.07 mol). The reaction was stirred for 2 hours, then, 65 mL of DCC solution was added drop-wise, and after another 1 hour of stirring in an ice bath, the last 65 mL of DCC solution was added drop- wise. The reaction was stirred at room temperature over night. The mixture was filtrated by vacuum filtration and washed with DMF 2X50 mL. The solvent was evaporated and EtOAc was added (1400 mL), the organic phase washed with 90 mL of 5% citric acid, 60 mL of 10% citric acid, and 100 mL of saturated NaHCO3, dried over Na2SO4 and evaporated to yield a beige solid. The product was dissolved in IPA (300 mL) by heating to reflux. When the solution became clear-yellow the solution was cooled to room temperature and stirred over night. The product was isolated by vacuum filtration, washed isopropanol, and dried in a vacuum oven at 4O0C overnight to obtain tert-butyl (R)-4-(3-(trifluoromethyl)-5,6-dihydro- [l,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-l-(2,4,5-trifluorophenyl)-4-oxobutan-2-yl- carbamate (52 g, 85 % yield).

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; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2009/64476; (2009); 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. 5049-61-6, name is Pyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C4H5N3

A solution of aminopyrazine (1 g, 10.5 mmol) and chloroacetaldehyde (50% wt in H2O; 1.98 g, 12.6 mmol) in 1.6 mL of EtOH was heated at 900C in a sealed tube for 5 h. Upon cooling to ambient temperature, the reaction mixture was concentrated and diluted with dichloromethane (DCM). The organic layer washed with saturated aqueous NaHCO3 then dried over MgSO4 and concentrated. The crude product was purified by silica gel flash chromatography (eluted with 10% MeOH/DCM) to provide 0.8 g of product.

According to the analysis of related databases, 5049-61-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ARIAD PHARMACEUTICALS, INC.; WO2007/75869; (2007); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 56423-63-3, name is 2-Bromopyrazine, 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 56423-63-3, Recommanded Product: 2-Bromopyrazine

General procedure: A mixture of methyl 4-bromobenzoate2a (100 mg, 0.465 mmol), methyl N-(tert-butoxycarbonyl)glycinate 3a (132 mg, 0.698 mmol), Pd2(dba)3 (8.5 mg,9.3 lmol), Xantphos (16 mg, 0.028 mmol), and cesium carbonate(303 mg, 0.930 mmol) was charged with dioxane (1.0 mL). Theresulting suspension was sparged with argon via subsurface bubblingfor 5 min, and the reaction mixture was sealed and stirredat 100 C for 12 h. The reaction was cooled to ambient temperature,diluted with EtOAc (20 mL), and filtered to remove the inorganicsalts. The filtrate was concentrated to an oil, then purified bycolumn chromatography on silica gel, eluting with an EtOAc/hexanesgradient (2-30%) to afford the desired product 4a as a colorlessgum (75% isolated yield). 1H NMR (500 MHz, DMSO-d6): d 7.90(d, J = 9.0 Hz, 2H), 7.40 (d, J = 8.5 Hz, 2H), 4.39 (s, 2H), 3.83 (s, 3H),3.68 (s, 3H), 1.37 (s, 9H). LRMS (ESI) calcd for C16H21NO6 (M+Na)+:346.1, found: 346.1.

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

Reference:
Article; Falcone, Danielle; Osimboni, Ekundayo; Guerin, David J.; Tetrahedron Letters; vol. 55; 16; (2014); p. 2646 – 2648;,
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. 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C6H7N3O2

Example 3a Methyl 3-amino-6-iodopyrazine-2-carboxylate 1.5 equivalents of N-iodosuccinimide are added at room temperature to 5 g (32.7 mmol) of a methyl 3-aminopyrazine-2-carboxylate solution in 25 ml of dimethylformamide The reaction medium is heated at 65 C. for 1 hour, added together with 0.5 equivalents of N-iodosuccinimide and maintained at 65 C. for 24 hours. After returning to room temperature, the solvent is evaporated and then the product is extracted several times with dichloromethane. The organic phases are combined, washed with 10% sodium bisulfite solution, dried on magnesium sulfate and concentrated to yield 8 g (88%) of methyl 3-amino-6-iodopyrazine-2-carboxylate in the form of a yellow solid. LCMS (EI, m/z): (M+1) 280 1H NMR: deltaH ppm (400 MHz, DMSO): 8.50 (1H, s, CHarom), 7.50 (2H, bs, NH2), 3.20 (3H, s, CH3).

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 16298-03-6.

Reference:
Patent; PIERRE FABRE MEDICAMENT; KALOUN, El Bachir; BEDJEGUELAL, Karim; RABOT, Remi; KRUCZYNSKI, Anna; SCHMITT, Philippe; PEREZ, Michel; RAHIER, Nicolas; US2013/85144; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem