Pyrazines

Electric Literature of 21948-70-9, These common heterocyclic compound, 21948-70-9, name is 2-Methylthiopyrazine, 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.

To a solution of AgClO4 (137mg, 0.67mmol) in MeCN (1mL), 2-methylthiopyrazine (84mg, 0.67mmol) was added and the mixture was stirred at ambient temperature for 5min. The resulting solution was filtered and Et2O (6mL) was then layered on a filtrate. The mixture was left overnight at 5C. The precipitated X-ray quality crystals were collected and dried in air. Yield: 210mg (95%). FT-IR (KBr, cm-1): 413 (w), 432 (vw), 494 (vw), 625 (s), 696 (vw), 741 (w), 762 (w), 843 (m), 974 (m), 1084 (vs), 1144 (s), 1292 (w), 1393 (w), 1441 (w), 1466 (w), 1508 (w). Anal. Calcd: C10H12Ag2Cl2N4O8S2 (663.76): C, 18.0; H, 1.8; N, 8.4; S, 9.6 Found: C, 18.2; H, 1.9; N, 8.5; S, 9.8.

Statistics shows that 2-Methylthiopyrazine is playing an increasingly important role. we look forward to future research findings about 21948-70-9.

Reference:
Article; Rogovoy, Maxim I.; Berezin, Alexey S.; Kozlova, Yuliya N.; Samsonenko, Denis G.; Artem’ev, Alexander V.; Inorganic Chemistry Communications; vol. 108; (2019);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 5049-61-6, A common heterocyclic compound, 5049-61-6, name is Pyrazin-2-amine, molecular formula is C4H5N3, 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.

To avoid over chlorination, milder conditions were examined. No reaction was observed at RT, but a complete transformation into the dichloro derivative was observed at 50C.

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; THE GOVERNMENT OF THE UNITED STATES, as represented by the secretary of HEALTH AND HUMAN SERVICES; WO2007/124345; (2007); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

58139-04-1, name is 2-Iodo-3-methoxypyrazine, 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. name: 2-Iodo-3-methoxypyrazine

Step 1: To a stirred mixture of sodium iodide (4.89 g, 32.67 mmol) and 2-iodo-3-methoxypyrazine (2.57 g,10.89 mmol) in acetonitrile (30 mL) at rt was added trimethylsilyl chloride (3.55 g, 32.67 mmol). The mixture was heatedat 70 C for 1.5 h. The mixture was cooled to rt and partitioned between a mixture of DCM, MeOH, and aq 2 M HCl. Theorganic layer was separated and the aqueous layer was extracted with additional DCM/MeOH mixture. The combinedorganic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to afford 3-iodopyrazin-2(1H)-one (1.21 g, 50%) as a brown solid that did not require further purification. 1H NMR (500 MHz, DMSO-d6) delta 12.54(br s, 1H), 7.42 (d, J = 3.7 Hz, 1H), 7.17 (d, J = 3.7 Hz, 1H); LCMS (ESI) m/z 223 (M+H)+.

The synthetic route of 58139-04-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Ambit Biosciences Corporation; HADD, Michael J.; HOCKER, Michael D.; HOLLADAY, Mark W.; LIU, Gang; ROWBOTTOM, Martin W.; XU, Shimin; (299 pag.)EP2766359; (2016); B1;,
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. 50866-30-3, name is 5-Methylpyrazine-2-carbaldehyde, A new synthetic method of this compound is introduced below., Product Details of 50866-30-3

A vial was charged with C65 (100 mg, 0.33 mmol), and the vial was evacuated and flushed with nitrogen; this procedure was repeated twice, tetrahydrofuran (1.6 mL) was added, and the solution was cooled to -78 C. 2,2,6,6-Tetramethylpiperidinylmagnesium chloride, lithium chloride complex (1 M solution in tetrahydrofuran and toluene; 0.497 mL, 0.497 mmol) was added, and the reaction mixture was allowed to stir for 1 hour at -78 C. In a separate vial, 5-methylpyrazine-2- carbaldehyde (80.9 mg, 0.662 mmol) was dissolved in tetrahydrofuran (1.6 mL), and the resulting solution was cooled in a dry ice/acetone bath for 10 minutes. This solution wasthen added to the reaction mixture, which was subsequently allowed to stir while slowly warming to 15 C. After 1 hour, it was combined with two similar reaction mixtures derived from C65 (50 mg, 0.17 mmol; 100 mg, 0.33 mmol), and the resulting mixture was diluted with water (20 mL) and extracted with ethyl acetate (3 x 15 mL). The combined organic layers were concentrated in vacuo and subjected to reversed-phaseHPLC (Column: Phenomenex Synergi Max-RP, 10 pm; Mobile phase A: 0.1% trifluoroacetic acid in water; Mobile phase B: acetonitrile; Gradient: 15% to 45% B), affording a diastereomeric mixture of 14 and 15 as a viscous, brick-red oil. Combined yield of diastereomeric mixture: 180 mg, 0.425 mmol, 51%. This material was separated into its component diastereomers via supercritical fluid chromatography [Column: Regis Technologies, (S,S)-Whelk-O 1, 10 pm; Mobile phase: 3:2 carbon dioxide I (ethanol containing 0.1 % ammonium hydroxide)]. The firsteluting diastereomer, obtained as a light yellow solid, was designated as 14. Yield: 58.6mg, 0.138 mmol, 32% for the separation. LCMS m/z 423.9 (chlorine isotope pattern observed) [M+H]. 1H NMR (400 MHz, CD3OD) 9.12 (br s, 1 H), 8.92 (5, 1 H), 8.83-8.74 (brs, 1H), 8.48 (5, 1H), 8.18 (d, J=9.0 Hz, 1H), 7.74 (dd, J=9.0, 2.0 Hz, 1H), 6.51 (5, 1 H), 5.58-5.46 (m, 1 H), 4.29 (dd, J=1 1.8, 5.3 Hz, 1 H), 3.80-3.66 (br m, 1 H), 3.66-3.52 (br m, 1H), 2.79-2.66 (m, 1H), 2.60 (5, 3H), 2.42-2.27 (br m, 1H), 2.13-2.00 (br m, 1H),1.77-1.63 (brm, 1H), 1.28 (brd, J=5.5 Hz, 3H).The second-eluting diastereomer, also isolated as a light yellow solid, was designated as 15. Yield: 56.8 mg, 0.134 mmol, 32% for the separation. LCMS m/z 423.9 (chlorine isotope pattern observed) [M+H]. 1H NMR (400 MHz, CD3OD) 9.12 (br s, 1 H), 8.92 (5, 1 H), 8.82-8.74 (br s, 1 H), 8.47 (br s, 1 H), 8.18 (d, J=8.5 Hz, 1 H),7.74 (dd, J=9.0, 2.0 Hz, 1H), 6.50 (5, 1H), 5.57-5.46 (m, 1H), 4.21 (dd, J=11.8, 4.8 Hz,1 H), 3.82-3.70 (br m, 1 H), 3.62-3.47 (br m, 1 H), 2.71-2.57 (br m, 1 H), 2.59 (5, 3H),2.48-2.35 (m, 1H), 2.24-2.13(brm, 1H), 1.63-1.50 (brm, 1H), 1.34(d, J=6.0 Hz, 3H).

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; PFIZER INC.; BRODNEY, Michael Aaron; CHAPPIE, Thomas Allen; CHEN, Jinshan Michael; COE, Jotham Wadsworth; COFFMAN, Karen Jean; GALATSIS, Paul; GARNSEY, Michelle Renee; HELAL, Christopher John; HENDERSON, Jaclyn Louise; KORMOS, Bethany Lyn; KURUMBAIL, Ravi G.; MARTINEZ-ALSINA, Luis Angel; PETTERSSON, Martin Youngjin; REESE, Matthew Richard; ROSE, Colin Richard; STEPAN, Antonia Friederike; VERHOEST, Patrick Robert; WAGER, Travis T.; WARMUS, Joseph Scott; ZHANG, Yuan; (193 pag.)WO2018/163066; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 78342-42-4, These common heterocyclic compound, 78342-42-4, name is (S)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine, 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.

An oven-dried microwave vial (2.0 – 5.0 mL volume) was charged with (2S)-2- isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (100 uL, 0.56 mmol). The reaction vial was flushed with argon, sealed with a cap and then further flushed with argon. Dry THF (2 mL) was added. The reaction vessel was cooled to -78 ¡ãC and n-BuLi (1.59M in hexanes; 0.74 mL, 1.18 mmol) was added dropwise. The reaction mixture was stirred at -78 ¡ãC for 30 min. 2- Bromoethanol (40 uL, 0.56 mmol) was added dropwise and the reaction mixture was allowed to warm to rt and stirred for 4h. The reaction mixture was cooled to 0 ¡ãC and a solution of 4- methylbenzenesulfonyl chloride (106 mg, 0.56 mmol) in THF (1 mL) was added. The reaction mixture was allowed to warm to rt and stirred for 2h. The reaction mixture was quenched with saturated aq. NH4CI (5 mL) and the aqueous mixture was extracted with DCM (3 x 10 mL). The organic extracts were combined, dried (Na2S04) and concentrated in vacuo. Purification by flash chromatography (25 g KP-SIL; 0percent to 40percent EtOAc in cyclohexane) afforded 2- [(2f?,5S)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazin-2-yl]ethyl 4-methylbenzenesulfonate (cf.r. >20: 1 , 107 mg) as a viscous yellow oil. LCMS (Method T2) Rt 1.60 min; m/z 383.1639 [M+H]+

The synthetic route of 78342-42-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; BELLENIE, Benjamin Richard; CARTER, Michael Keith; CHEUNG, Kwai Ming Jack; DAVIS, Owen Alexander; HOELDER, Swen; LLOYD, Matthew Garth; VARELA RODRIGUEZ, Ana; (381 pag.)WO2018/215801; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 6164-79-0, 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. 6164-79-0 name is Methyl 2-pyrazinecarboxylate, 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.

A stirred solution of methyl 2-pyrazinecarboxylate(4.94 g, 35.8 mmol) in methanol (350 mL)was slowly added sodium borohydride (5.410 g, 143 mmol)in 1 g portions over 10 min. Caution: The solution becameyellow and evolved heat and gas, add the sodium borohydridecautiously. The solution was stirred overnightat room temperature. H2O (20 mL) was added and thereaction was shaken vigorously. The suspension was thenevaporated to dryness under reduced pressure to an oilyyellow powder. Ethyl acetate (350 mL) was then added andthe resulting suspension was stirred vigorously overnight.The suspension was filtered and evaporated to drynessunder vacuum to give the crude product as a yellow oilwhich was used without further purification (2.80 g, ca.71%). 1H NMR (300 MHz, CDCl3): delta (ppm) 8.64 (br, 1H, H-3),8.53 (m, 1H, H-2), 8.50 (m, 1H, H-1), 4.84 (s, 2H, CH2).

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

Reference:
Article; Feltham, Humphrey L. C.; Cowan, Matthew G.; Kitchen, Jonathan A.; Jameson, Guy N. L.; Brooker, Sally; Supramolecular Chemistry; vol. 30; 4; (2018); p. 296 – 304;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 912773-21-8, name is 2-Bromo-5-chloropyrazine, 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 912773-21-8, Application In Synthesis of 2-Bromo-5-chloropyrazine

A mixture of 2-bromo-5-chloro-pyrazine (229.4 mg, 1.19 mmol), [5-fluoro-6-(2,2,2- trifluoro-1-methyl-ethoxy)-3-pyridyl]boronic acid (300 mg, 1.19 mmol), Pd(dppf)Cl2 (130.16 mg, 0.18 mmol) and CS2CO3 (772.77 mg, 2.37 mmol) in 1,4-dioxane (10 mL) and water (1 mL) was stirred at 60 C for 5 hours under N2. After cooling to r.t., the mixture was diluted with _0 (30 mL), and the mixture was extracted with EtOAc (50 mL x 2). The combined organic phase was washed with water (20 mL x 2) and brine (20 mL), dried over Na2S04, filtered and concentrated to give the crude product. The crude product was purified by flash chromatography on silica gel (EtOAc in PE = 0% to 1% to 3% ) to give the product (210 mg, 0.64 mmol) as a solid. The product was analyzed by SFC to show two peaks (Peak 1: Rt = 2.02 min, Peak 2: Rt = 2.28 min). Method: Column: Chiralpak AD-3 150 x 4.6mm I.D, 3_ Mobile phase: A: C02 B:ethanol (0.05% DEA), Gradient: from 5% to 40% of B in 5 min and hold 40% for 2.5 min, then 5% of B for 2.5 min Flow rate: 2.5mL/min Column temp.: 35 C. 1H NMR (400MHz CDC13) _ = 8.77 (d, 1H), 8.65 (d, 1H), 8.53 (d, 1H), 8.08 (dd, 1H), 5.95 – 5.85 (m, 1H), 1.63 -1.48 (m, 3H). LCMS Rt = 0.92 min in 1.5 min chromatography, 5-95AB, purity 98.54%, MS ESI calcd. for Ci2H9ClF4N30 [M+H]+ 322.0, found 321.9

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

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 6966-01-4, A common heterocyclic compound, 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, molecular formula is C6H6BrN3O2, 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.

0.15 eq. palladium (II) acetate and 0.2 eq. 1,1′-bis(diphenylphosphino)-ferrocene were combined in dimethylformamide under nitrogen and heated to 50 C. for 20 minutes. Het is as defined herein. The reaction was allowed to cool to room temperature and 1.0 eq. of the pyrazine, 1.5 eq. of the boronic acid and 1.15 eq. of triethylamine were added. The reaction was heated to 90 for 12 hours and allowed to cool to room temperature. The DMF was removed by rotary evaporation. The crude reaction mixture was dissolved in chloroform and washed twice with 1N aq. HCl and then twice with saturated aq. NaHCO3 solution. The organic layer was dried over sodium sulfate, filtered and concentrated. Material was purified by silica gel chromatography using 100% chloroform as eluent.

The synthetic route of 6966-01-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Pfizer Inc; US2004/180905; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 1379338-74-5, name is 5,7-Dichloropyrido[3,4-b]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. Recommanded Product: 5,7-Dichloropyrido[3,4-b]pyrazine

Intermediate 5: 1,1-Dimethylethyl (3R)-3-{[(7-chloropyrido[3,4-b]pyrazin-5-yl)amino]methyl}-1-piperidinecarboxylate 5,7-dichloropyrido[3,4-b]pyrazine (1 g, 5.00 mmol) was taken up in N-Methyl-2-pyrrolidone (NMP) (10 ml) and treated with 1,1-dimethylethyl (3R)-3-(aminomethyl)-1-piperidinecarboxylate (1.179 g, 5.50 mmol) (Apollo Scientific Ltd) and diisopropylethylamine (1.310 ml, 7.50 mmol). The reaction was irradiated in a Biotage microwave at 130 C. for 30 min. The reaction was partitioned between EtOAc (100 ml) and water (100 ml). The organic layer was washed with brine (100 ml), dried using a hydrophobic frit and concentrated to give a black solid. This solid was purified on silica (50 g) 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 (1.542 g). LCMS (Method B): Rt=1.28 min, MH+=377.92

The synthetic route of 5,7-Dichloropyrido[3,4-b]pyrazine has been constantly updated, and we look forward to future research findings.

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.; US2014/5188; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 486424-37-7, A common heterocyclic compound, 486424-37-7, name is 3-Amino-6-bromopyrazine-2-carboxylic acid, molecular formula is C5H4BrN3O2, 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.

Triethyl amine (0.57 ML, 4.13 mmol) was added to a mixture of 3-AMINO-6-BROMO-2- pyrazinecarboxylic acid (0.30 g, 1.38 mmol; described in: Ellingson, R. C.; Henry, R. L. J. Am. Chem. Soc. 1949,2798-2800), 0- (BENZOTRIAZOL-1-YL)-NNN’, N’- tetramethyluroniumtetrafluoroborate (0.486 g, 1.51 mmol) and 1-hydroxybenzotriazole (0.204 g, 1.51 mmol) in N, N-DIMETHYLFORMAMIDE/ACETONITRILE, (1: 1,5 ML). After stirring for 0.5 h at room temperature, 2-(LH-PYRROL-L-YL)-L-ETANAMINE (0.182 g, 1.65 mmol) was added and the resulting mixture was stirred overnight at room temperature. Approximately, 10 ML water was added and a precipitation was formed. The precipitation was filtered and washed with water which gave 0.21 g (50% yield) of a light brown solid: MS (ESP) M/Z 310,312 (M++1). The solid (0.16 g, 0.516 mmol) from previous step was dissolved in tetrahydrofuran/water (5: 1,5 mL) together with [4- [ (4-methyl-l-piperazinyl) sulfonyl] phenyl] boronic acid (0.220 g, 0.77 mmol), sodium carbonate (0.164 g, 1.55 mmol) and Pd (dppf) CL2 (0.013 g, 1.5 nmmol). The resulting mixture was stirred at 70 C overnight (N2-atmosphere). The mixture was evaporated onto silica and purified on silica using toluene/acetonitrile, (1: 2 to 1: 4), as the eluent which afforded a yellow solid which was dried in vacuo at 40 C. The product was dissolved in a methylene chloride/methanol mixture, (9: 1), and hydrochloride acid in diethyl ether (0.28 mL, 1 M) was added. The precipitate was washed with diethyl ether and dried in vacuo to give 69 mg (23% yield) of the title compound : 1H NMR (DMSO-d6) 5 8.94 (s, 1 H), 8.90 (t, J = 6 Hz, 1 H), 8.43 (d, J = 8 Hz, 2 H), 7.82 (d, J = 8 Hz, 2 H), 6.79 (t, J = 2 HZ, 2 H), 6.01 (t, J = 2 HZ, 2 H), 4.12 (t, J = 7 Hz, 2 H), 3.83 (d, J = 12 Hz, 2 H), 3.63 (quart, J = 6 Hz, 2 H), 3.44 (d, J = 12 Hz, 2 H), 3.15 (m, 2 H), 2.73 (m, 5 H) ; 13C NMR (DMSO-d6) 8 165.8, 154.5, 144.8, 140.8, 135.9, 133.3, 127.9, 126.1, 124.6, 120.7, 107.8, 51.5, 47.6, 43.0, 41.8 ; MS (ESP) M/Z 470 (M++1).

The synthetic route of 486424-37-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; WO2004/55009; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem