Tag: M.W=200-300

These common heterocyclic compound, 622392-04-5, name is 2-Bromo-5-iodopyrazine, 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. Recommanded Product: 2-Bromo-5-iodopyrazine

2-Bromo-5-iodopyrazine [CAS RN: 622392-04-5] (3.50 g, 12.3 mmol, 1.0 eq),4,4,5,5-tetramethyl-2-(prop-1 -en-2-yl)-1 ,3,2-dioxaborolane [CAS RN: 126726-62-3] (3.10 g, 18.4 mmo[, 1.5 eq), Pd(dppf)C[2.CH2C[2 (502 mg, 0.61 mmo[, 0.05 eq) and cesium carbonate (12.0 g, 36.9 mmo[, 3.0 eq) were dissolved in 130 mL dioxane/water (5/1). The reaction mixture was heated to 90C for 2 h. On cooling, the reaction mixture was partitioned between water anddichloromethane. The organic phase was washed with brine and the phases were separated by the use of a Whatman filter. The volatile components were removed in vacuo and the crude material was purified via preparative MPLC (Biotage Isolera; 100 g SNAP cartridge: hexane -> hexane/ethyl acetate 9/1) to give 600 mg (25% yield of theory) of the title compound in a round 50% purity(UPLC-area%). The impurity was identified as 2,5-di(prop-1-en-2-yl)pyrazine, that was not expected to interfere in the subsequent reaction step. The material obtained was used without further purification.UPLC-MS (Method 4): R = 1.18 mm; MS (ESI0): m/z = 199 [M].

The synthetic route of 2-Bromo-5-iodopyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BAeRFACKER, Lars; SIEMEISTER, Gerhard; HEINRICH, Tobias; PRECHTL, Stefan; STOeCKIGT, Detlef; ROTTMANN, Antje; WO2015/113927; (2015); A1;,
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Synthetic Route of 369638-68-6, A common heterocyclic compound, 369638-68-6, name is tert-Butyl (5-methylpyrazin-2-yl)carbamate, molecular formula is C10H15N3O2, 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 2: To a solution of (5-methyl-pyrazin-2-yl)-carbamic acid tert-butyl ester (from above and from example 21, step 1, 12.9 g, 61.6 mmol) and AIBN (10.1 g, 61 mmol) in CCl4 (100 mL) was added NBS (11 g, 61.6 mmol) and the reaction mixture was stirred at 100 C. for 4 h. The reaction mixture was filtered, washed with CH2Cl2 and concentrated in vacuo. Purification by chromatography (silica, 4:5:1 CH2Cl2:hexanes:ethyl acetate) with repurification of mixed fractions by chromatography (silica, 4:5:1 CH2Cl2:hexanes:ethyl acetate) afforded a total of (5-bromomethyl-pyrazin-2-yl)-carbamic acid tert-butyl ester (13.6 g, 77%): 1H NMR (300 MHz, CHLOROFORM-d) delta ppm 1.57 (s, 9H) 4.55 (s, 2H) 8.15 (s, 1H) 8.34 (d, J=1.51 Hz, 1H) 9.28 (d, J=1.51 Hz, 1H).

The synthetic route of 369638-68-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Brotherton-Pleiss, Christine E.; Walker, Keith A. M.; US2012/149718; (2012); A1;,
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Synthetic Route 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;,
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Pyrazine | C4H4N2 – PubChem

Reference of 143591-61-1, These common heterocyclic compound, 143591-61-1, name is 3-Bromo-8-chloroimidazo[1,2-a]pyrazine, 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-8-chloroimidazo [1,2-a] pyrazine (1.33 g, 5.7 mmol),1- (2-methoxyethyl) -1H-pyrazole-4-amine (0.96 g, 6.8 mmol) was added to 15 mL of n-butanol,The temperature was raised to 120 C and reacted overnight.The solvent was removed by rotary evaporation, diluted with 30 mL of water, and extracted with ethyl acetate (20 mL * 3). The organic phases were combined,It was washed with 20 mL of saturated brine, dried over anhydrous sodium sulfate, and concentrated.Separation through a silica gel column gave 1.45 g of a pale yellow solid with a yield of 76%.

The synthetic route of 143591-61-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shenzhen Tajirui Bio-pharmaceutical Co., Ltd.; Wang Yihan; Xing Qingfeng; Ai Yixin; (85 pag.)CN110272426; (2019); A;,
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Electric Literature of 1458-18-0,Some common heterocyclic compound, 1458-18-0, name is Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, molecular formula is C6H5Cl2N3O2, 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.

Methyl 3-amino 5,6-dichloro-2-pyrazinecarboxylate (10 g, 45 mmol) was placed in a three-necked round bottom flask flushed with nitrogen, equipped with a bubbler and a gas condensor. The round bottomedflask and condensor were cooled to -80 C using a dry ice in acetone bath. Gaseous ammonia (500 mL) was condensed into the flask over a period of 1.5 h. Thereaction mixture was allowed to warm to reflux and maintained at reflux for a period of10 h. The ammonia then was allowed to evaporate from the flask (fume hood!) and the solid obtained was dried under high vacuum overnight to provide 3-amino-5,6-dichloro-2-pyrazinecarboxamide 4 (9.5 g, 100%) as solid,

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate, its application will become more common.

Reference:
Article; Massey, Archna P.; Harley, William R.; Pasupuleti, Nagarekha; Gorin, Fredric A.; Nantz, Michael H.; Bioorganic and Medicinal Chemistry Letters; vol. 22; 7; (2012); p. 2635 – 2639;,
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Reference of 1379338-74-5,Some common heterocyclic compound, 1379338-74-5, name is 5,7-Dichloropyrido[3,4-b]pyrazine, molecular formula is C7H3Cl2N3, 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.

Intermediate 5: 1 ,1-Dimethylethyl (3 ~)-3-fr(7-chloropyridor3,4-blpyrazin-5- yl)amino1methviyi-piperidinecarboxylate; 5,7-dichloropyrido[3,4-b]pyrazine (1g, 5.00mmol) was taken up in N-Methyl-2- pyrrolidone (NMP) (10ml) and treated with 1 , 1-dimethylethyl (3f~)-3-(aminomethyl)-1- piperidinecarboxylate (1.179g, 5.50mmol) (Apollo Scientific Ltd) and diisopropylethylamine (1.310ml, 7.50mmol). The reaction was irradiated in a Biotage microwave at 130C for 30min. The reaction was partitioned between EtOAc (100ml) and water (100ml). The organic layer was washed with brine (100ml), dried using a hydrophobic frit and concentrated to give a black solid. This solid was purified on silica (50g) and eluted with a 10-40% EtOAc/cyclohexane gradient. The appropriate fractions were combined and concentrated to give the title compound as a deep orange solid (1.542g).LCMS (Method B): Rt = 1.28min, MH+ = 377.92

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5,7-Dichloropyrido[3,4-b]pyrazine, its application will become more common.

Reference:
Patent; GLAXO GROUP LIMITED; ATKINSON, Francis Louis; ATKINSON, Stephen John; BARKER, Michael David; DOUAULT, Clement; GARTON, Neil Stuart; LIDDLE, John; PATEL, Vipulkumar Kantibhai; PRESTON, Alexander G; SHIPLEY, Tracy Jane; WILSON, David Matthew; WATSON, Robert J; WO2012/123312; (2012); A1;,
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Electric Literature of 76537-18-3,Some common heterocyclic compound, 76537-18-3, name is 3-Bromo-5-chloropyrazin-2-amine, molecular formula is C4H3BrClN3, 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.

To a degassed solution of 3-bromo-5-chloro-pyrazin-2-amine, la, (20.80 g, 99.79 mmol), Et3N (41.74 mL, 299.4 mmol), iodocopper (0.6 g, 2.99 mmol) and dichloropalladium; triphenylphosphine (1.40 g, 2.00 mmol) in THF (388 mL) was added ethynyl-trimethyl-silane (14.10 mL, 99.79 mmol) over 5 minutes. The reaction mixture was warmed to 55 C for 1 hour. The reaction mixture was cooled to room temperature and filtered through a pad of celite. The filtrate was concentrated in vacuo and the resulting solid was washed with ether and filtered to provide 14 g of the desired product (62% yield) in sufficient purity for use in the subsequent reaction: XH NMR (400 MHz, CDC13) delta 7.94 (s, 1H), 5.00 (d, J = 44.2 Hz, 2H), 0.26 (s, 9H) ppm; LCMS Gradient 10-90%, 0.1% formic acid, 5 min, C18/ACN, RT = 3.42 min (M+H) 226.39.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Bromo-5-chloropyrazin-2-amine, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARIFSON, Paul, S.; LEDEBOER, Mark, W.; CLARK, Michael, P.; BOYD, Michael, J.; GAO, Huai; LEDFORD, Brian; MALTAIS, Francois; PEROLA, Emanuele; WO2013/184985; (2013); A1;,
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Electric Literature of 1159811-97-8, 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. 1159811-97-8, name is 6-Bromo-2-methylimidazo[1,2-a]pyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

In a sealed tube, 4-bromo-2-ethoxybenzamide (288 mg, 0.1.18 mmol), 6-bromo-2- methylimidazo[l,2-a]pyrazine (275 mg, 1.30 mmol), copper (I) iodide (22.5 mg, 0.118 mmol, 0.1 eq.), K3PO4 (526 mg, 2.48 mmol, 2.1 eq.) and 1,10-phenantroline (42.5 mg, 0.236 mmol, 0.2 eq.) in dioxane (5 mL) was heated at 120C overnight. The reaction mixture was filtered on celite, concentrated under vacuo, and purification on column chromatography (S1O2, CH2C12 / MeOH 99/1 to 98/2) afforded 159 mg (36%) of the title product as a white solid. MS (m/e): 375.2 (M+H+, Br).

The synthetic route of 6-Bromo-2-methylimidazo[1,2-a]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; GREEN, Luke; PINARD, Emmanuel; RATNI, Hasane; WILLIAMSON, Patrick; (95 pag.)WO2015/197503; (2015); A1;,
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Reference of 1458-01-1, A common heterocyclic compound, 1458-01-1, name is Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate, molecular formula is C6H7ClN4O2, 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: Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate 2 (1 eq.) was combined with K2CO3 (10 eq.), the appropriate (het)aryl boronic acid (1.5 eq.) and Pd(PPh3)4 (5 mol%) in a two-neck round bottom flask. The flask was connected to a condenser and purged with nitrogen. A 4:1 mixture of anhydrous toluene: MeOH (60 mL) was added via syringe and the reaction mixture was heated at reflux for 0.5-18 h. The mixture was allowed to cool to room temperature and filtered through Celite (10 x 3 cm, eluting with 3 x 20 mL EtOAc). The filtrate was evaporated to dryness and the residue purified by silica gel flash column chromatography using EtOAc/pet spirit.

The synthetic route of 1458-01-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Buckley, Benjamin J.; Majed, Hiwa; Aboelela, Ashraf; Minaei, Elahe; Jiang, Longguang; Fildes, Karen; Cheung, Chen-Yi; Johnson, Darren; Bachovchin, Daniel; Cook, Gregory M.; Huang, Mingdong; Ranson, Marie; Kelso, Michael J.; Bioorganic and Medicinal Chemistry Letters; vol. 29; 24; (2019);,
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Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 143591-61-1, name is 3-Bromo-8-chloroimidazo[1,2-a]pyrazine, 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 143591-61-1, Formula: C6H3BrClN3

To a solution of compound 2 (example 1, step 2) (80 mg, 0,28 mmoi) in THE (5 mL) was added NaH (22 mg, 0.56 mmoi, 60 wt% in oil) at RI. The mixture was stirred at RT for 30 minutes, then the product from step 1 (81 rng, 0.35 mmoi) was added. The mixture was heated to 60C for 3 hours. After cooling to RT, the mixture was poured into water (5 mL) and extracted with EtOAc (5 niL x 3). The combined organic layer was washed with brine, driedover MgSO4, filtered and concentrated in vacuo. The residue was purified by Prep.?FIPLC to afford the title compound (70 mg) as a white solid. LRMS mz (M+H) 482.1, 484.1 found, 482.1,484.1

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-8-chloroimidazo[1,2-a]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIVERTON, Nigel; KUDUK, Scott D.; BESHORE, Doug C.; MENG, Na; LUO, Yunfu; (127 pag.)WO2016/101119; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem