Category: 4949-13-7

Electric Literature of 4949-13-7, 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 4949-13-7 as follows.

(6-chloropyridin-2-yl)(3-fluoropyrazin-2-yl)methanone2,2,6,6-tetramethylpiperidine (1.729 g, 2.066 mL, 12.24 mmol) was dissolved in THF (20.00 mL) and cooled to -30 C under nitrogen. BuLi (4.488 mL of 2.5 M, 1 1.22 mmol) was added dropwise and the reaction allowed to warm to 0 C. Stir at this temperature for 10 minutes then cooled to -78 C. A solution of 2-fluoropyrazine (1 g, 10.20 mmol) in THF (4.000 mL) was added slowly and the mixture stirred at -78 C for lh. Methyl 6-chloropyridine-2-carboxylate (1.750 g, 10.20 mmol) in THF (6.000 mL) was added dropwise at between -78 and -70C, stirred at -78C for lh. Reaction quenched with 5% citric acid at -78 C then allow to warm to ambient temperature. Diluted with EtOAc and separated layers. Extracted with EtOAc (xl) then wash combined organics with aHCOs (xl), brine (xl). Dried (MgS04), filtered and concentrated. Crude product purified by ISCO companion (80 g S1O2, 0 to 50% EtO Ac/petrol) to leave title compound as an orange oil (1.12g, 46%). ¾ NMR (DMSO-d6) delta 7.90 (dd, 1H), 8.22 – 8.15 (dd, 2H), 8.67 (dd, 1H), 8.84 (dd, 1H). ES+ 238.13.

According to the analysis of related databases, 4949-13-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; JIMENEZ, Juan-Miguel; SETTIMO, Luca; FRAYSSE, Damien; BRENCHLEY, Guy; DAVIS, John, Christopher; MILLER, Andrew, W.; WO2011/94288; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 4949-13-7, The chemical industry reduces the impact on the environment during synthesis 4949-13-7, name is 2-Fluoropyrazine, I believe this compound will play a more active role in future production and life.

General procedure: To a 5 mL vial containing a stir bar, 3-(2-aminopyrimidin-5-yl)-6-cyclobutyl-2-fluorophenol (80 mg, 0.31 mmol) and 2-chloropyrimidine (41 mg, 0.34 mmol) were added Cs2CO3 (203 mg, 0.62 mmol) and DMSO (0.8 mL). The resultant mixture was stirred at 120 Celsius for approximately 1 hour via microwave irradiation. The reaction mixture was cooled to room temperature before passing the mixture through a syringe filter and subjecting the filtrate to FCC to afford the title compound (81 mg, 78%). The title compound was prepared using conditions similar to those described in Example 160 with DMSO as the solvent, heating for 2 hours at 80 Celsius via microwave radiation and substituting Intermediate B and 2-fluoropyrazine. MS (ESI): mass calcd. for C18H16FN6O, 337.13; m/z found, 337.9 [M+H]+. 1H NMR (400 MHz, CDCl3) delta 8.53 (d, J=1.3 Hz, 1H), 8.49-8.42 (m, 1H), 8.27 (d, J=2.7 Hz, 1H), 8.12-8.03 (m, 2H), 7.85-7.76 (m, 1H), 7.23 (s, 1H), 4.70 (s, 2H), 3.68-3.56 (m, 1H), 2.26-2.08 (m, 4H), 2.03-1.89 (m, 1H), 1.87-1.76 (m, 1H).

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, 2-Fluoropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; Eccles, Wendy; Fitzgerald, Anne E.; Hack, Michael D.; Hawryluk, Natalie A.; Jones, William M.; Keith, John M.; Krawczuk, Paul; Lebsack, Alec D.; Liu, Jing; Mani, Neelakandha S.; McClure, Kelly J.; Meduna, Steven P.; Rosen, Mark D.; US2014/221310; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 4949-13-7, A common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, molecular formula is C4H3FN2, 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.

10264] To a 2.5 M solution of n-butyllithium (40 mE, 0.1 mol) in anhydrous THF (250 mE) cooled to -78 C. under N2 protection was added TMP (2,2,6,6-tetramethylpiperidine, 15 g, 0.106 mol) dropwise over a period of 20 minutes. The mixture was warmed to 0 C. by replacing the dry ice/acetone bath with an ice bath and stirred for 1.5 h. The mixture was cooled back to -78C. and a solution of 9a (3 g, 0.03 mol) and tributyltin chloride (10 g, 0.03 mol) in SOmE of dry THF was added over 10 mm. The mixture was stirred at -78 C. for 6 h, then warmed to -40 C. by replacing the dry ice/acetone bath with an dry ice/acetonitrile bath. A solution of 35% HC1, ethanol and THF (1:4:5) was added. The mixture was warmed to room temperature and washed with saturated NaHCO3 solution (100 mE) and extracted with EtOAc (3×100 mE). The combined organic layers were dried over anhydrous Na2504 and concentrated under reduced pressure. The residue was purified by column chromatography (silica, EtOAc:petroleum ether=1:15) to provide 9b (3.4 g, 29% yield) as light yellow oil. ?H-NMR (CDC13, 300 MHz): oe=8.41 (d, 1H), 8.17 (d, 1H), 1.8-0.53 (m, 27H).

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; Helsinn Healthcare SA; Giuliano, Claudio; Garcia Rubio, Silvina; Daina, Antoine; Guainazzi, Angelo; Pietra, Claudio; US2015/252021; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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 4949-13-7 as follows. Recommanded Product: 2-Fluoropyrazine

A solution of 2-fluoropyrazine (0.247 mL, 3.06 mmol), 2-amino-1-(piperidin-1-yl)ethanone hydrochloride (710 mg, 3.98 mmol) and DIPEA (1.603 mL, 9.18 mmol) in acetonitrile (5 mL) was heated to 100 C for 16 h. The reaction mixture was concentrated and then dissolved in ethyl acetate (15 mL) and water (20 mL). The organic Layer was washed and separated. The aqueous layer was then washed with ethyl acetate (5 x 15 mL). The organic layers were combined, dried through a hydrophobic frit and concentrated in vacuo. The crude material was purified using silica chromatography with a gradient of 0-80 % (3:1 ethyl acetate:ethanol + 1 % triethylamine)/cyclohexane. The relevant fractions were combined and concentrated in vacuo to yield 1-(piperidin-1-yl)-2-(pyrazin-2-ylamino)ethanone (415 mg, 1.88 mmol, 61 % yield) as an orange solid. LCMS (High pH, ES+): tR = 0.67 min, [M+H]+ 221.16. 1H NMR (400 MHz, CDCl3) delta 1.55-1.64 (m, 4H), 1.65-1.73 (m, 2H), 3.39-3.44 (m, 2H), 3.60-3.66 (m, 2H), 4.13 (d, J = 3.79 Hz, 2H), 5.88 (br. s., 1H), 7.79 (d, J = 3.03 Hz, 1H), 7.95-7.98 (m, 1H), 8.02 (d, J = 1.26 Hz, 1H) 13C NMR (101 MHz, CDCl3) delta 24.4, 25.5, 26.2, 42.5, 43.3, 45.4, 132.6, 134.0, 141.4, 153.8, 166.6 HRMS: (C11H16N4O) [M+H]+ requires 221.1397, found [M+H]+ 221.1391 numax (neat): 3328, 2941, 2857, 1639, 1586, 1531, 1436, 1251, 1230, 1000, 820, 615 cm-1.

According to the analysis of related databases, 4949-13-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Law, Robert P.; Ukuser, Sabri; Tape, Daniel T.; Talbot, Eric P. A.; Synthesis; vol. 49; 16; (2017); p. 3775 – 3793;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 4949-13-7,Some common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, molecular formula is C4H3FN2, 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 in hexanes, 1.05 mL, 2.58 mmol) was added to a solution of 2,2,6,6-tetramethylpiperidine (462 muL, 2.73 mmol) in THF (10 mL) at -78 C. The reaction mixture was stirred at 0 C. for 20 min. A solution of 2-fluoropyrazine (224 mg, 2.28 mmol) in THF was added at -78 C. After stirring at -78 C. for 5 min, ZnCl2 (0.5 M in THF, 11 mL, 5.32 mmol) was then added. The reaction mixture was stirred at -78 C. for 30 min and then at 0 C. for 1 h. A solution of the bromide (500 mg, 1.52 mmol) and Pd(PPh3)4 (352 mg, 0.304 mmol) in THF (20 mL) was then added. The reaction mixture was stirred at rt for 3 days. A sat. aq. solution of EDTA was added. After stirring at rt for 15 min, a sat. aq. solution of NaHCO3 was added. The reaction mixture was extracted with DCM. The combined organics were separated, dried (MgSO4), filtered and concentrated. The crude residue was purified by SiO2 chromatography eluting with 20:80 EtOAc/hexane to afford 200 mg (38%) of pyrazine as a yellow oil. MS m/z (ES): 346 (M+H)+.

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

Related Products of 4949-13-7, A common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, molecular formula is C4H3FN2, 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 sodium sulfite (3.86 g, 30.6 mmol) in water (20 mL) was added 2-fluoropyrazine (2 g, 20.4 mmol). It was stirred at 150C under pressure tube overnight. After removal of solvent, the solid was dried to give crude product sodium pyrazine-2-sulfonate as a white solid (6 g) which was used directly for next step without further purification.

The synthetic route of 4949-13-7 has been constantly updated, and we look forward to future research findings.

Application of 4949-13-7, A common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, molecular formula is C4H3FN2, 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: (R)-4-N-Boc-2-methylpiperazine (665 mg, 3.32 mmol), 1-adamantoyl chloride (990 mg, 4.98 mmol), and DIEA (1.15 mL, 6.64 mmol) were dissolved in 2.0 mL of dichloromethane, and the reaction was monitored by LCMS. Upon completion, 5.0 mL of MeOH was added, and the mixture was concentrated in vacuo. The residue was purified by flash chromatography. The purified product was immediately dissolved in 1.0 mL of MeOH and excess 4 N HCl in dioxanes (4.0 mL, 16 mmol). Once the protecting group had cleaved as judged by LCMS, an aqueous solution of saturated sodium bicarbonate was added until the pH was basic. The mixture was extracted with dichloromethane, and the organic layers were concentrated in vacuo to afford 814 mg (94% yield) of adamantan-1-yl((R)-2-methylpiperazin-1-yl)methanone as a white solid. Adamantan-1-yl((R)-2-methylpiperazin-1-yl)methanone (355 mg, 1.35 mmol) and 2-cyano-3-fluoropyridine (1.42 mL, 5.41 mmol) were dissolved in 4.0 mL of NMP in a microwave reaction vial and heated in the microwave for 10 min at 250 C. The reaction mixture was purified via reverse phase chromatography (0.1% TFA in H2O/MeCN). The fractions containing the product were combined and neutralized by the addition of aqueous saturated sodium bicarbonate. The mixture was extracted with dichloromethane, and the organic layers were combined and concentrated in vacuo. The residue was dissolved in 1.0 mL of MeOH and 4 N HCl in dioxanes (3.0 mL, 12 mmol) and stirred for 2 h. The mixture was concentrated in vacuo to afford 212 mgs (39% yield) of the HCl salt as a yellow solid.

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:
Article; Lovell, Kimberly M.; Felts, Andrew S.; Rodriguez, Alice L.; Venable, Daryl F.; Cho, Hyekyung P.; Morrison, Ryan D.; Byers, Frank W.; Daniels, J. Scott; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A.; Bioorganic and Medicinal Chemistry Letters; vol. 23; 13; (2013); p. 3713 – 3718;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

4949-13-7, name is 2-Fluoropyrazine, 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: C4H3FN2

Example 65(4-cyclobutylpiperazin-1-yl)(7-(pyrazin-2-yl)-7-azaspiro[3.5]nonan-2-yl)methanone A mixture of Intermediate 7 (100 mg, 0.34 mmol), 2-fluoropyrazine (141 mg, 1.44 mmol), DIEA (0.6 mL, 3.44 mmol) and DMSO (1 mL) was heated to 130 C. for 30 min in a Biotage Initiator microwave oven. The reaction mixture was injected on a preparative HPLC UV using a high pH shallow gradient method (Mobile phase: 30-50% B; A: H2O with 15 mM NH4CO3 and 0.375% NH4OH v/v, B: CH3CN, 30 min. run) on XBridge Prep C18 OBD, 30¡Á150 mm, 10 mum, Waters reverse phase column, to provide title compound (76 mg, 59.9%) as a solid. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.59-1.68 (m, 2H) 1.68-1.82 (m, 4H) 1.91 (br. s., 2H) 1.99-2.12 (m, 4H) 2.13-2.24 (m, 2H) 2.30 (br. s., 4H) 2.74 (quin, J=7.52 Hz, 1H) 3.22 (quin, J=8.69 Hz, 1H) 3.39 (br. s., 2H) 3.45-3.53 (m, 2H) 3.54-3.62 (m, 2H) 3.65 (br. s., 2H) 7.79 (d, J=2.34 Hz, 1H) 8.03 (dd, J=2.73, 1.56 Hz, 1H) 8.14 (s, 1H); HRMS m/z calcd for C21H32N5O 370.2601 [M+H]+, found 370.2604.

The synthetic route of 4949-13-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; US2010/130477; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 4949-13-7,Some common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, molecular formula is C4H3FN2, 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.

[0222] To a mixture of (A)-4-( l -aminocthyljhcnzonitrilc (1.0 g, 6.8 mmol, 1.0 equiv) and IPA (15 mL) in a microwave vial (20 mL) were added 2-fluoropyrazine (0.81 g, 8.2 mmol, 1.2 equiv) and DIPEA (2.1 g, 16.4 mmol, 2.4 equiv). The vial was sealed and heated at 170 C in a microwave reactor for 4 h. The mixture was concentrated onto 5 g of Si02 and purified by silica gel chromatography (40 g column, 0-10% MeOH in DCM) to provide (/?)- 4-(l-(pyrazin-2-ylamino)ethyl)benzonitrile. LRMS (ES) m/z 225.1 (M+H). 1 H-NMR (Methanol-74, 400 MHz, ppm) d 7.92 (t, J = 1.7 Hz, 1H), 7.85 (dd, 7 = 2.9, 1.5 Hz, 1H), 7.70 – 7.63 (m, 2H), 7.61 (d, 7 = 2.9 Hz, 1H), 7.58 – 7.52 (m, 2H), 5.08 (q, 7 = 7.1 Hz, 1H), 1.54 (d, 7 = 7.0 Hz, 3H).

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

Reference:
Patent; CYTOKINETICS, INC.; MORGAN, Bradley P.; VANDERWAL, Mark; CHUANG, Chihyuan; (0 pag.)WO2020/5888; (2020); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 4949-13-7, A common heterocyclic compound, 4949-13-7, name is 2-Fluoropyrazine, molecular formula is C4H3FN2, 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.

Example 8. Preparation of 4,5,6, 7-tetrahydro-5-(5-methoxypyridin-3-yl)-Lambda/-(pyrazin-2- yl)thiazolo[5,4-c]pyridin-2-amine (Compound 18)[00121] As shown in step 8-i of Scheme 8, to a solution of 5-(5-methoxypyridin-3-yl)- 4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-amine (Compound 1026, 20 mg, 0.076 mmol) in NMP (1 mL) was added 2-fluoropyrazine (22.4 mg, 0.229 mmol) and Cs2CO3 (149 mg, 0.46 mmol). The reaction mixture was heated 110 0C for 18 h. The crude mixture was purified by medium pressure silica gel chromatography (0 to 10% MeOH in DCM) followed by a second purification using reversed-phase chromatography (5 to 90 % CHsCN/water). Fractions containing pure produce were brought to a neutral pH and the product isolated as the bis-HCl salt to give 4,5,6,7-tetrahydro-5-(5-methoxypyridin-3-yl)-Lambda/-(pyrazin-2-yl)thiazolo[5,4- c]pyridin-2-amine (Compound 18, 4 mg): ESMS (M+H) 341.13; 1H NMR (CD3OD, 300MHz) delta 8.65 (d, J=I.5 Hz, IH), 8.51 (t, J= 1.5Hz, IH), 8.41 (d, J=2.7Hz, IH), 8.22 (d, J=2.4 Hz, 1H),7.96 (d, J=2.4 Hz, 1H),7.69 (t, J=2.4 Hz, IH), 4.67 (s, 2H), 4.04 (s, 3H), 3.98 (t, J=5.7 Hz, 2H), 3.01 (t, J=5.7 Hz, 2H) ppm.

The synthetic route of 4949-13-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; ARONOV, Alex; BANDARAGE, Upul, Keerthi; COTTRELL, Kevin; DAVIES, Robert; KRUEGER, Elaine; LEDEBOER, Mark; LEDFORD, Brian; LE TIRAN, Arnaud; LIAO, Yusheng; MESSERSMITH, David; WANG, Tiansheng; XU, Jinwang; WO2010/96389; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem