Tag: M.W=100-200

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. name: 2,6-Dichloropyrazine

General procedure: To the N,N-dimethylformamide (DMF) (4 mL) solution of N,N-dimethylethylenediamine (95 mL, 0.87 mmol) was added K2CO3 (0.19 g, 1.3 mmol). After the reaction mixture was stirred at room temperature (RT) for 30 min, 2,6-dichloropyrazine (0.10 g, 0.67 mmol) was added and the resulting reaction mixture was further stirred at RT for 12 h. After removal of solvent in vacuo, the residue was treated with dichoromethane. Insoluble impurities were removed by filtration. Removal of solvent in vacuo gave the product 0.095 g in 71 % yield;

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4774-14-5, its application will become more common.

Reference:
Article; Lee, Jinho; Park, Jongseong; Hong, Victor Sukbong; Chemical and Pharmaceutical Bulletin; vol. 62; 9; (2014); p. 906 – 914;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 63286-28-2, 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. 63286-28-2 name is 2-Chloro-3-hydrazinylpyrazine, 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.

Intermediate b (5.0 g, 0.034 mol) was added to triethyl orthoformate (50 mL), and the reaction was carried out at 80 C. The reaction time was monitored with a plate. The reaction liquid was directly filtered with cold suction, and the filter cake was washed with petroleum ether. After the cake was dried, 4.8 g of a yellow powder was obtained with a yield of 90.1%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-3-hydrazinylpyrazine, and friends who are interested can also refer to it.

Reference:
Patent; Jiangxi Science and Technology Normal University; Zhu Wufu; Zheng Pengwu; Liu Xiaobo; Xu Shan; Zhang Qian; Tang Qidong; Zhou Hualan; Wu Jinjin; Yuan Ping; Zhang Hongbo; (25 pag.)CN110407839; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 914452-71-4, A common heterocyclic compound, 914452-71-4, name is 2-Bromo-6-methylpyrazine, molecular formula is C5H5BrN2, 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.

n-Butyllithium (2.5M solution in hexane, 2.57 mL, 6.43 mmol) was added dropwise to 2-bromo-6-methylpyrazine (1060 mg, 6.13 mmol) in DCM (6 mL) at -78 C under nitrogen. 4H-spiro[benzo[d]isoxazole-7,1′-cyclopropan]-5(6H)-one (500 mg, 3.06 mmol) in DCM (1.5 mL) was added dropwise after the mixture had been stirred for 30 min. The mixture was stirred at -78 C for 1.5 h under 2, quenched with sat. aq. NaHCCb (20 mL) and extracted with DCM (3 x 20 mL). The combined organic layers were washed with brine (1 x 25 mL), dried over Na2S04, fdtered and evaporated. The crude product was purified by silica gel chromatography (45 to 50% EtOAc in petroleum ether). Pure fractions were evaporated to dryness to afford 5-(6-methylpyrazin-2-yl)-5,6-dihydro-4H-spiro[benzo[d]isoxazole-7,1′-cyclopropan]-5-ol (200 mg, 25.4 %) as a yellow foam. XH NMR (400 MHz, CDCb) d ppm 0.58 (ddd, J = 9.2, 7.3, 4.0 Hz, 1H), 1.01 (ddd, J = 9.1, 7.3, 4.0 Hz, 1H), 1.35 (ddd, J = 9.8, 7.3, 3.9 Hz, 1H), 1.76 (ddd, J= 9.9, 7.3, 3.9 Hz, 1H), 2.58 (d, J= 7.5 Hz, 1H), 2.61 (s, 3H), 2.63 (d, J = 4.4 Hz, 1H), 2.85 (dd, J = 16.0, 1.5 Hz, 1H), 3.22 (d, J = 16.0 Hz, 1H), 4.14 (s, 1H), 8.13 (s, 1H), 8.45 (s, 1H), 8.61 (s, 1H). m/z (ES+), [M+H]+ = 258; HPLC (C05)tR = 0.663 min (92.3%).

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; MEDIMMUNE LIMITED; BARTHOLOMEUS, Johan; BUeRLI, Roland; JARVIS, Rebecca; JOHNSTONE, Shawn; OSTENFELD, Thor; TERSTIEGE, Ina; TRAVAGLI, Massimiliano; TURCOTTE, Stephane; (203 pag.)WO2019/122265; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 109838-85-9, 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. 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, This compound has unique chemical properties. The synthetic route is as follows.

[0487] To a dry-ice / acetone cooled solution of Scheme 5-8 compound S5 (5 g, 0.027 mol) in THF (50 ml), was dropwise added n-BuLi (2.5 M, 14.1 mL, 0.035 mol) for 30 min. After addition, the reaction was stirred at this temperature for 30 min, followed by dropwise addition of a solution of Scheme 5-8 compound S4 (13.6 g, 0.04 mol) in THF (20 mL). The reaction mixture was stirred at this temperature for another 30 min and allowed to stir at room temperature for 16 h. The reaction was quenched with aq. NHtCl (50 mL) and extracted with ethyl acetate (60 mL x 2). The combined organic fractions were washed with brine, dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluted with petroleum ether: ethyl acetate =10: 1) to afford the title compound (6 g, yield 50.4%) and Scheme 5-8 compound S6 (4.8 g) was recovered.

The chemical industry reduces the impact on the environment during synthesis (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ACHILLION PHARMACEUTICALS, INC.; WILES, Jason, Allan; PHADKE, Avinash, S.; DESHPANDE, Milind; AGARWAL, Atul; CHEN, Dawei; GADHACHANDA, Venkat, Rao; HASHIMOTO, Akihiro; PAIS, Godwin; WANG, Qiuping; WANG, Xiangzhu; GREENLEE, William; (325 pag.)WO2017/35405; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

5521-58-4, name is 5-Methylpyrazin-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. Formula: C5H7N3

Palladium (II) acetate (lOmg) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene(40mg) were added to a mixture of S-4-chloro-6-methyl-2-{2-[3-(pyrid-2-yl)isoxazol-5- yl]pyrrolidin-l-yl}pyrimidine (272mg, 0.80mmol), 2-amino-5-methylpyrazine (85mg, 0.78mmol) and cesium carbonate in 1,4-dioxane (5ml) under nitrogen. The mixture was heated at 100C in a sealed vessel under microwave irradiation for 18 hours. The solution was allowed to cool, the insolubles were removed by filtration and the solvent was removed from the filtrate by evaporation. The residue was purified by column chromatography on silica gel eluting with EtOAc / hexane (25:75 increasing in polarity to 0:100). The purified product was triturated with ether and hexane and the solid collected by filtration to give the title compound (174mg, 53%); NMR (398K) 2.03-2.15 (2H, m), 2.15-2.20 (IH, m), 2.15 (3H, s), 2.35-2.45 (IH, m), 2.38 (3H, s), 3.70-3.75 (IH, m), 3.76-3.84 (IH, m), 5.45-5.55 (IH, m), 6.48 (IH, s), 6.65 (IH, s), 7.40-7.46 (IH, m), 7.85-7.90 (IH, m), 7.90-7.95 (IH, d), 8.10 (IH, s), 8.61-8.65 (IH, d), 9.10 (IH, s), 9.30-9.35 (IH, br s); m/z 415 [MH]+ .

The synthetic route of 5521-58-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2007/31745; (2007); A1;,
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

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

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

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 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