Month: July 2021

Reference of 13924-95-3,Some common heterocyclic compound, 13924-95-3, name is Methyl 5-hydroxypyrazine-2-carboxylate, molecular formula is C6H6N2O3, 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.

Example 9 6-Cyclopropylmethoxy-5-piperidin-1-yl-pyrazine-2-carboxylic acid ((S)-1-hydroxymethyl-3-methyl-butyl)-amide a) 5-Methanesulfonyloxy-pyrazine-2-carboxylic acid methyl ester; A mixture of 3.34 g (22 mmol) methyl 5-hydroxypyrazine-2-carboxylate (commercially available), 2.73 g (24 mmol) methane sulfonyl chloride and 3.29 g (33 mmol) NEt3 in 40 mL DCM was stirred at room temperature for 4 h. Water and Na2CO3 was added and the organic layer was separated and dried with MgSO4. Evaporation yielded 3.7 g (73%) of the title compound which was used without further purification. 300-MHz-1H-NMR (DMSO): delta=9.06 (d, J=1.2 Hz, 1H, 3-H), 8.83 (d, J=1.2 Hz, 1H, 6-H), d=3.97 (s, 3H, OMe), 3.74 (s, 3H, SO2Me).

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

Reference:
Patent; Dietz, Michel; Gruener, Sabine; Hebeisen, Paul; Meyer Reigner, Sylvie C.; Nettekoven, Matthias; Puellmann, Bernd; Roever, Stephan; Ullmer, Christoph; US2008/85905; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 4774-14-5,Some common heterocyclic compound, 4774-14-5, name is 2,6-Dichloropyrazine, molecular formula is C4H2Cl2N2, 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.

[0685] To a solution of fert-butyl azetidin-3-ylcarbamate hydrochloride (LXXX) (2 g, 9.58 mmol) in dry DMF (19.2 mL) was added DIPEA (8.37 ml, 47.9 mmol). To this mixture was added 2,6-dichloropyrazine (LXXXI) (1.428 g, 9.58 mmol) and the reaction was stirred at 95C for 3 h. The reaction was quenched with water (20 mL) and extracted with EtOAc. The organic layer was dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by silica gel column chromatography (40 g) (100% hexanes?hexanes:EtOAc 1 : 1) to yield fert-butyl (l-(6-chloropyrazin-2-yl)azetidin-3-yl)carbamate (LXXXII) (2.2882 g, 8.04 mmol, 84 % yield) as a white solid. ESIMS found for C12H17CIN4O2 mlz 285.1 (M+H).

The synthetic route of 4774-14-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SAMUMED, LLC.; KC, Sunil Kumar; WALLACE, David Mark; CAO, Jianguo; CHIRUTA, Chandramouli; HOOD, John; (251 pag.)WO2017/24013; (2017); 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. 22047-25-2, name is Acetylpyrazine, A new synthetic method of this compound is introduced below., Formula: C6H6N2O

To a suspension of palladium (II) acetate (59 mg, 0.26 mmol), XANTPHOS (76 mg, 0.13 mmol) and tripotassium phosphate (3.9 g, 18 mmol) in dioxane (10 mL)/THF (2.7 mL)/toluene (2.7 mL) was added 1-(pyrazin-2-yl)ethanone (1.6 g, 13 mmol) and 1-bromo-2- fluorobenzene (0.72 mL, 6.6 mmol). The reaction mixture was degassed with nitrogen, sealed, and heated to 100 C for 18 hours, after which it was filtered through Celite and washed with several volumes of EtOAc. The filtrate was concentrated to a residue which was purified using silica gel chromatography utilizing a gradient of 1 to 10% methanol in dichloromethane to afford 2-(2-fluorophenyl)-1-(pyrazin-2-yl)ethanone (250 mg, 17 % yield) as an orange solid.1H NMR (500 MHz, methanol-d4) (ppm) 9.19 (s, 1 H), 8.85 (d, 1 H), 8.80 (m, 1 H), 7.31 – 7.34 (m, 2 H), 7.15 – 7.18 (m, 1 H), 7.09 – 7.13 (m, 1 H), 4.62 (s, 2 H).

The synthetic route of 22047-25-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; IRONWOOD PHARMACEUTICALS, INC.; RENNIE, Glen, Robert; BARDEN, Timothy, Claude; LEE, Thomas, Wai-Ho; IYENGAR, Rajesh, R.; NAKAI, Takashi; MERMERIAN, Ara; JIA, James; IYER, Karthik; IM, G-Yoon, Jamie; RENHOWE, Paul, Allan; JUNG, Joon; GERMANO, Peter; TANG, Kim; (240 pag.)WO2018/89330; (2018); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 5521-55-1, These common heterocyclic compound, 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, 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.

[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 (3×100 mL). The combined organic extracts were washed with water (1×100 mL), a mixture of a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution (1:1, 1×100 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 (1×20 mL), a saturated aqueous sodium bicarbonate solution (1×20 mL) and water (1×20 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.

The synthetic route of 5521-55-1 has been constantly updated, and we look forward to future research findings.

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

Electric Literature of 54608-52-5, These common heterocyclic compound, 54608-52-5, name is 2-Hydrazinopyrazine, 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.

[1337] a mixture of 2-hydrazineylpyrazine (2 g, 18.16 mmol) and ethyl 2,4-dioxopentanoate (2.87 g, 18.16 mmol) in AcOH (40 ml) was stirred at 118 C for 1 hour. The reaction mixture was concentrated under reduced pressure to remove AcOH. The residue was diluted with H2O (8 ml), adjusted to ph ~ 7 with Na2CO3, and then extracted with DCM (200 ml x 3). The combined organic layers were washed with brine (20 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The residue was purified by flash silica gel chromatography (isco; 40 g sepaflash silica flash column, eluent of 0-20% ethyl acetate/petroleum ethergradient 40 ml/min). Compound 285a (1.5 g, 35.57% yield) was obtained as a white solid. Compound 285a: 1H NMR (400mhz, CDCl3) delta 8.98 – 8.93 (m, 1h), 8.60 – 8.54 (m, 1h), 8.46 – 8.41 (m, 1h), 6.78 (s, 1h), 4.34 – 4.25 (m, 2h), 2.38 (s, 3h), 1.27 (t, =7.2 hz, 3h).

The synthetic route of 54608-52-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BLADE THERAPEUTICS, INC.; BUCKMAN, Brad, Owen; YUAN, Shendong; ADLER, Marc; EMAYAN, Kumaraswamy; MA, Jingyuang; (687 pag.)WO2018/64119; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 486424-37-7, name is 3-Amino-6-bromopyrazine-2-carboxylic acid, molecular formula is C5H4BrN3O2, 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: 486424-37-7

Step 3 : 5-Bromo-3-(6-methyl-lH-benzo [d] imidazol-2-yl)pyrazin-2-amine[00141] A mixture of 3-amino-6-bromo-pyrazine-2-carboxylic acid (5.52g, 25.32 mmol), 4-methylbenzene-l,2-diamine (3.09g, 25.32 mmol), diethoxyphosphorylformonitrile (4.54, 27.85 mmol) and triethylamine (7.06 mL, 50.64 mmol) in DME (30 mL) was heated in the microwave at 170C for 60 minutes. The mixture was diluted with ethyl acetate, washed with water followed by aqueous aHC03 then brine. After drying over MgSC^, the mixture was decolourised with charcoal and filtered through silica gel. After concentration, the mixture was filtered to give gold coloured crystals (4.005g, 52% Yield). MS (ES+) 305.0.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 486424-37-7, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-Damien; DURRANT, Steven, John; KNEGTEL, Ronald, Marcellus, Alphonsus; O’DONNELL, Michael; REAPER, Philip, Michael; WO2011/143419; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 33332-28-4, These common heterocyclic compound, 33332-28-4, name is 2-Amino-6-chloropyrazine, 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.

Preparation of 3-bromo-6-chloropyrazin-2 -amine (B-10-3).-10-2 B-10-3 B-10-3bTo a solution of compound B-10-2 (110 g, 0.85 mol) in CHCI3 (1.5 L) was added N-bromo-succinimide (151.3 g, 0.85 mol) portionwise at O0C under N2 atmosphere. After the addition, the reaction mixture was warmed to room temperature and stirred overnight. TLC (petroleum ether/EtOAc 3:1 ) indicated most of compound B-10-2 was consumed. The reaction mixture was washed with saturated Na2CO3 (1 L x 3), H2O (1 L x 3) and saturated aqueous NaCI (1 L) in sequence, dried over Na2SO4 and concentrated in vacuo. The residue was purified via column chromatography (silica gel, EtOAc/hexane 1 :20) to yield pure B-10-3b (35 g) and pure compound B-10-3 (45 g, 28%) as a yellow solid.

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

Reference:
Patent; PFIZER INC.; WO2009/16460; (2009); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 54608-52-5, These common heterocyclic compound, 54608-52-5, name is 2-Hydrazinopyrazine, 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 1To 2-hydrazinopyrazine (1.60 g, 14.55 mmol) was added 4-chloro-benzoic acid (3 eq) followed by 20 mL of polyphosphoric acid, and the reaction mixture was stirred at 110 C for 18 h. The hot PPA solution was added to ice and neutralized by the addition of ammonium hydroxide (highly exothermic.). The aqueous solution was extracted with ethyl acetate, washed with brine, and dried over anhydrous sodium sulfate. Concentration followed by flash chromatography (silica gel, 1 : 1 hexanes: ethyl acetate) afforded 3-(4-chlorophenyl)- [l,2,4]triazolo[4,3-a]pyrazine, as a viscous oil.

Statistics shows that 2-Hydrazinopyrazine is playing an increasingly important role. we look forward to future research findings about 54608-52-5.

Reference:
Patent; AMGEN INC.; BREGMAN, Howard; BUCHANAN, John, L.; CHAKKA, Nagasree; DIMAURO, Erin, F.; DU, Bingfan; NGUYEN, Hanh, Nho; ZHENG, Xiao, Mei; WO2011/103196; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 19847-12-2,Some common heterocyclic compound, 19847-12-2, name is Pyrazinecarbonitrile, molecular formula is C5H3N3, 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-Cyanopyridine (0.420 ml; 4 mmol) was dissolved in absolute methanol (20 ml) and to it was added sodium methoxide solution in methanol (1.0 ml) (previously prepared). The reaction contents were stirred at room temperature for 2 h 1,4-diaminobutane (0.18 ml, 2 mmol) was added to the reaction mixture. Reaction contents were heated under reflux for 12 h. Solvent was removed under reduced pressure. Crude product so obtained was washed with diethyl ether and then with ethyl acetate to give thick mass. Solvent traces from this thick mass was removed by applying high vacuum for 15 min to give semisolid product i.e. N-(2-pyridineimidoylamino-butyl)-pyridine-2-carboxamidine (5a). Yield 480 mg (81%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Pyrazinecarbonitrile, its application will become more common.

Reference:
Article; Arya, Surbhi; Kumar, Nikhil; Roy, Partha; Sondhi; European Journal of Medicinal Chemistry; vol. 59; (2013); p. 7 – 14;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 17231-51-5, 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. 17231-51-5, name is 3-Amino-6-bromopyrazine-2-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows.

Step 1: 3-Amino-6-bromo-N?-hydroxypyrazine-2-carboximidam ide To a 20m1 flask was added 3-amino-6-bromopyrazine-2-carbonitrile (600 mg, 3.01 mmol) inMeOH (12 ml) and cooled to 000. To the reaction mixture was added hydroxylaminehydrochloride (210 mg, 3.01 mmol) and triethylamine (0.420 ml, 3.01 mmol) and the mixturewas allowed to warm to room temperature as a precipitate formed. The precipitate was filtered off and washed with MeOH. The filtrate was concentrated under reduced pressure and the resulting solid triturated in MeOH to give a second crop of product. The solid was triturated in MeOH again and sonicated for l5mins until a suspension formed. The solid wasfiltered off and dried in a vacuum oven at 40C for 3 hours to afford the title compound;1H NMR (400MHz, DMSO-d6), O 10.38 (1H, 5), 8.15 (1H, 5), 7.64 (2H, brs), 5.88 (2H, 5).

The chemical industry reduces the impact on the environment during synthesis 3-Amino-6-bromopyrazine-2-carbonitrile. 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