Category: 76537-18-3

Adding a certain compound to certain chemical reactions, such as: 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, 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 76537-18-3, category: Pyrazines

Step 1: 5-Chloro-3-((trimethylsilyl)ethynyl)pyrazin-2-amineTo a 500 mL round-bottomed flask was added 3-bromo-5-chloropyrazin-2-amine (5 g, 23.99mmol), ethynyltrimethylsilane (10.17 ml, 72.0 mmol), and triethylamine (33.4 ml, 240 mmol)in THF (100 ml) to give a brown solution. The reaction was degassed and purged withnitrogen. To the stirring solution was added bis(triphenylphosphine)palladium(ll) chloride (1.684g, 2.399mmo1) and copper(l) iodide (914mg, 4.8Ommol). The reaction was stirred at room temperature for 30mins. The reaction was extracted into ethyl acetate, washed with brine, the organic layer separated, dried over Mg504, filtered and the solvent removed underreduced pressure. The crude product loaded onto silica was purifiied by flash column chromatography elution with iso hexane:ethyl acetate (0-30%) using an 80g silca cartridge. The required fractions were combined and the solvent removed under reduced pressure to yield a brown solid;LCMS: Rt = 1 .29mins MS mlz 226.2 [M+H]+; Method 2minLowpHvo2.1H NMR (400MHz, DMSO-d6) O 8.08 (1H, 5), 6.82 (2H, broad 5), 0.27 (9H, 5).

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, 3-Bromo-5-chloropyrazin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NOVARTIS AG; BELLENIE, Benjamin Richard; BLOOMFIELD, Graham Charles; BRUCE, Ian; CULSHAW, Andrew James; HALL, Edward Charles; HOLLINGWORTH, Gregory; NEEF, James; SPENDIFF, Matthew; WATSON, Simon James; (395 pag.)WO2015/162459; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 76537-18-3, A common heterocyclic compound, 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, molecular formula is C4H3BrClN3, 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.

3-Bromo-5-chloropyrazin-2-amine (200 mg, 0.96 mmol),Triethylamine (290 mg, 2.88 mmol), cuprous iodide(5mg, 0.33mmol)And bis(triphenylphosphine)palladium dichloride (13 mg, 0.02 mmol) was dissolved in tetrahydrofuran (5 mL).The reaction solution was stirred at room temperature.Then trimethylethynyl silicon (0.15 mL, 1.06 mmol)Slowly adding dropwise to the above reaction solution,After completion of the dropwise addition, the resulting reaction solution was heated to 55 C to continue the reaction for 1 hour.After the reaction system is cooled to room temperature,The reaction solution was diluted with ethyl acetate (50 mL).Filter and concentrate the filtrate under reduced pressure.The residue obtained was purified by silica gel column chromatography (PE/EA (v/v) = 30/1).The title compound was obtained as a pale yellow solid ( 208 g, 96%).

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; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Ren Qingyun; Tang Changhua; Yin Junjun; Yi Kai; Lei Yibo; Wang Yejun; Zhang Yingjun; Nie Biao; Xu Juan; Yan Huan; Chen Jianping; (90 pag.)CN108727369; (2018); A;,
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. 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, A new synthetic method of this compound is introduced below., Recommanded Product: 3-Bromo-5-chloropyrazin-2-amine

3-Bromo-5-chloropyrazin-2-amine (200 mg, 0.96 mmol), triethylamine (290 mg, 2.88mmol), cuprous iodide (5 mg, 0.33 mmol) and palladium(II)bis(triphenylphosphine) dichloride(13 mg, 0.02 mmol) were dissolved in tetrahydrofuran (5 mL). The mixture was stirred at rt, thentrimethylsilylacetylene (0.15 mL, 1.06 mmol) was added dropwise to the mixture. After theaddition, the reaction mixture was warmed to 55 oc and stirred for 1 h. The reaction mixture wascooled to rt, and diluted with ethyl acetate (50 mL). The mixture was filtered. The filtrate wasconcentrated in vacuo, and the residue was purified by silica gel column chromatography(PE/EtOAc (v/v) = 3011) to give the title compound as a light yellow solid (208 mg, 96 %).MS (ESI, pos. ion) m/z: 227.00 [M+Ht;1H NMR (400 MHz, CDCh) 8 (ppm): 7.98 (s, 1H), 5.11 (s, 2H), 0.31 (s, 9H).

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; SUNSHINE LAKE PHARMA CO., LTD.; TANG, Changhua; REN, Qingyun; YIN, Junjun; YI, Kai; LEI, Yibo; WANG, Yejun; ZHANG, Yingjun; (303 pag.)WO2018/108125; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 76537-18-3, 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. 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows.

Intermediate C75-Chloro-3-( I ,3-dimethyl-I H-pyrazol-4-yl)-pyrazi n-2-ylam me To a solution of 3-bromo-5-chloropyrazin-2-amine (3.75 g, 18.01 mmol) in DME (90 mL) wasadded 1 ,3-dimethyl-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole (4 g, 18.01 mmol), bis(triphenylphosphine)palladium(ll) chloride (0.632 g, 0.901 mmol) and Na2003 (aq.2.OM) (27.0 mL, 54.0 mmol). The reaction was heated to 90C overnight. The reaction was added to water (250m1) and the product was extracted into EtOAc (2 x 230m1). The organic phase was washed with brine, dried over MgSO4. The solids were removed by filtration, washed with EtOAc and the filtrate concentrated under vacuum. The crude product was purified by flash column chromatography, eluting with 0-10% gradient of (2M NH3 in MeOH)in DCM on a 80g Si-column, loading with DCM to give the product (2.5g)LCMS: Rt 0.81 mins; MS mlz 224.0 [M+H]+; Method 2minLowpHvol

The chemical industry reduces the impact on the environment during synthesis 3-Bromo-5-chloropyrazin-2-amine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; NOVARTIS AG; BELLENIE, Benjamin Richard; BLOOMFIELD, Graham Charles; BRUCE, Ian; CULSHAW, Andrew James; HALL, Edward Charles; HOLLINGWORTH, Gregory; NEEF, James; SPENDIFF, Matthew; WATSON, Simon James; (395 pag.)WO2015/162459; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 76537-18-3, A common heterocyclic compound, 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, molecular formula is C4H3BrClN3, 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.

The suspension of 18a (3 g, 14.5 mmol), NaCN (0.85 g, 17.4 mmol), CuI (1.3 g, 7.3 mmol) and Pd(PPh3)4 (0.17 g, 0.15 mmol) were stirred in DMF (40 mL) at 120 C for 10 h under nitrogen protection. After cooling to room temperature, 10% aqueous solution of Na2S2O3(10 mL), water (60 mL) and ethyl acetate (200 mL) were added. The resulting mixture was stirred for 10 min, then filtered, and the filter cake was washed with ethyl acetate (150 mL). The organic layer was separated, washed with water (3 ¡Á 50 mL),dried over anhydrous Na2SO4and concentrated. The residue was purified by chromatography on silica gel eluting with PE/EA (10:1-2:1) to give a light-yellow solid (1.9 g, yield 85%). 6-Chloro-3-aminopyrazine-2-carbonitrile (19a) Yield: 85%, light-yellow solid, M.p.: 156-158 C. 1H NMR(400 MHz, CDCl3):delta 8.23 (s, 1H), 5.34 (s, 2H). 13C NMR(100 MHz, CDCl3):delta 154.98, 146.84, 137.41, 114.07,111.16. EI-MS m/z: 154 (M+, Cl35,100), 156 (M+, Cl37,35),127 (M+, Cl35,-H, -CN, 48), 129 (M+, Cl37,-H, -CN, 15).

The synthetic route of 76537-18-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Guo, Qi; Xu, Mingshuo; Guo, Shuang; Zhu, Fuqiang; Xie, Yuanchao; Shen, Jingshan; Chemical Papers; vol. 73; 5; (2019); p. 1043 – 1051;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

76537-18-3, name is 3-Bromo-5-chloropyrazin-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. COA of Formula: C4H3BrClN3

3-Bromo-5-chloropyrazin-2-amine (200 mg, 0.96 mmol), triethylamine (290 mg, 2.88 mmol), cuprous iodide (5 mg, 0.33 mmol) and bis(triphenyl) Palladium dichloride (13 mg, 0.02 mmol) was dissolved in tetrahydrofuran (5 mL).The reaction solution was stirred at room temperature.Then, trimethylethynyl silicon (0.15 mL, 1.06 mmol) was slowly added dropwise to the above reaction solution.After the completion of the dropwise addition, the obtained reaction liquid was transferred to a condition of 55 C to continue the reaction for 1 hour. After the reaction system is cooled to room temperature,The reaction solution was diluted with ethyl acetate (50 mL) and filtered.The filtrate was concentrated under reduced pressure.The residue obtained was subjected to silica gel column chromatography(PE/EA(nu/nu) = 30/1) purified,The title compound was obtained as a pale yellow solid (208 mg,96%).

The synthetic route of 76537-18-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Ren Qingyun; Tang Changhua; Yin Junjun; Wang Yejun; Yi Kai; Lei Yibo; Zhang Yingjun; S ¡¤geerdeman; Yan Huan; Nie Biao; Xu Juan; Chen Jianping; Chen Yunfu; Zhang Weihong; Cheng Lijun; Ye Weiliang; (197 pag.)CN110117285; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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

Related Products of 76537-18-3, 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. 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

A mixture of 3-bromo-5-chloro-pyrazin-2-amine (600 mg, 2.88 mmol), 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (397.48 mg, 3.17 mmol), Cs2C03 (1.88 g, 5.76 mmol) and Pd(dppf)Cl2 (210.62 mg, 0.29 mmol) in 1,4-Dioxane (5 mL) and Water (0.50 mL) was stirred at 70 C for 16 hours. After cooling to r.t., the mixture was concentrated to give the crude product. The crude product was purified by flash chromatography on silica gel (EtOAc in PE = 20% to 40% to 60% to 80%) to give the product (200 mg) as a solid. *H NMR (400MHz, CDC13) _ = 7.90 (s, 1H), 4.55 (br s, 2H), 2.40 (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, 3-Bromo-5-chloropyrazin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; PRAXIS PRECISION MEDICINES, INC.; REDDY, Kiran; MARTINEZ BOTELLA, Gabriel; GRIFFIN, Andrew, Mark; MARRON, Brian, Edward; (364 pag.)WO2018/98499; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 76537-18-3, These common heterocyclic compound, 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, 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.

A. 5-Chloro-3-(2-methylprop-1-en-1-yl)pyrazin-2-amine, 37a (0433) (0434) A mixture of 3-bromo-5-chloropyrazin-2-amine (41 g, 0.20 mol), 4,4,5,5-tetramethyl-2-(2-methylprop-1-en-1-yl)-1,3,2-dioxaborolane (34 g, 0.19 mol), Pd(dppf)Cl2 (3.0 g, 4.1 mmol), K2CO3 (85 g, 0.62 mol,) in dioxane (600 mL) and water (100 mL) was stirred for 24 h at 80 C. under N2. The reaction was allowed to cool to RT and then quenched by the addition of 1 L of water/ice. The resulting solution was extracted with EtOAc (2¡Á2 L). The organic layers were combined, dried (Na2SO4) and concentrated. The resulting black oil was used in the next step without further purification. Mass Spectrum (LCMS, ESI pos.): Calcd. for C8H10ClN3: 184.1 (M+H)+; found: 184.1.

Statistics shows that 3-Bromo-5-chloropyrazin-2-amine is playing an increasingly important role. we look forward to future research findings about 76537-18-3.

Reference:
Patent; Janssen Pharmaceutica NV; Meegalla, Sanath; Huang, Hui; Player, Mark R.; (53 pag.)US2016/9662; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application 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.

Zinc dust (activated by the procedure found in WO2011/143365, the disclosure of which is incorporated herein by reference in its entirety) (0.627 g, 9.59 mmol) was charged to a dry flask and suspended in DMA (2.5 mL). 1,2-Dibromoethane (0.031 mL, 0.36 mmol) and TMSCl (0.092 mL, 0.72 mmol) were added and the reaction was stirred for 25 min. tert-Butyl 3-iodoazetidine-1-carboxylate (2.04 g, 7.20 mmol, Oakwood) in DMA (6.0 mL) was added slowly to the mixture which was immersed in a water bath to keep the temperature below 65 C. The mixture was stirred for 1 hour and was degassed by bubbling a stream of nitrogen through the mixture for 5 minutes. (0976) A separate flask was charged with 3-bromo-5-chloropyrazin-2-amine (0.50 g, 2.4 mmol, D-L Chiral Chemicals), dichloro[1,1?-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.118 g, 0.144 mmol) and copper(I) iodide (0.057 g, 0.30 mmol). DMA (6.0 mL) was added, and the mixture was degassed by bubbling a stream of nitrogen through the mixture for 5 minutes. The solution containing the organozinc in DMA was added, excluding any remaining zinc solids. The reaction mixture was then heated at 80 C. for 30 min. Upon cooling to room temperature, the reaction mixture was partitioned between water and EtOAc. The aqueous layer was extracted with two additional portions of EtOAc. The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The product was purified by flash chromatography, eluting with a gradient from 0-100% EtOAc in hexanes to afford product (0.62 g, 90%). LCMS calculated for C12H18ClN4O2(M+H)+: m/z=285.1, found: 285.1. 1H NMR (400 MHz, CDCl3) delta 7.96-7.90 (s, 1H), 4.78-4.65 (s, 2H), 4.35-4.22 (m, 4H), 3.79-3.69 (p, J=7.4 Hz, 1H), 1.48-1.44 (s, 9H).

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