Month: September 2021

Related Products of 768-05-8,Some common heterocyclic compound, 768-05-8, name is Pyrazinoic acid hydrazide, molecular formula is C5H6N4O, 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.

2-Hydroxyacetophenone (0.1g; 0.73mmol), hydrazide 3c (0.1g; 0.73mmol) and acetic acid (0.20mL) were dissolved in methanol (5mL) and heated at 110C in an autoclave for 24h. After cooling to rt, the solid was filtered off, washed with methanol and dried over P2O5. The filtrate was diluted with water and left to crystallize at 4C for 24h. A second load of solid was filtered off, washed with water and methanol and dried over P2O5. The overall yield of yellow solid was 0.14g (74%; lit [37]. 63%). Rf=0.88 (CHCl3/MeOH 20:1). mp 237-239C. IR (KBr): numax, 3347; 1690; 1508; 1489; 1250; 1157; 1043; 1021cm-1. 1H NMR (300MHz, DMSO) delta 13.03 (s, 1H, OH), 11.53 (s, 1H, NH), 9.25 (s, 1H, Ar), 8.96-8.87 (m, 1H, Ar), 8.84-8.68 (m, 1H, Ar), 7.64 (dd, J=8.1, 1.5Hz, 1H, Ar), 7.43-7,16 (m, 1H, Ar), 7.02-6.73 (m, 2H, Ar), 2.46 (s, 3H, CH3). 13C NMR (75MHz, DMSO): delta 160.9, 160.4, 159.2, 148.5, 144.7, 144.6, 144.0, 132.2, 129.3, 119.6, 119.2, 117.8, 14.4. Anal. Calcd. for C13H12N4O2: C, 60.93; H, 4.72; N, 21.86; Found: C, 61.27; H, 4.83; N, 21.76.

The synthetic route of 768-05-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Hru?kova, Kate?ina; Pot??kova, Eli?ka; Hergeselova, Tereza; Liptakova, Lucie; Ha?kova, Pavlina; Mingas, Panagiotis; Kova?ikova, Petra; ?im?nek, Toma?; Vavrova, Kate?ina; European Journal of Medicinal Chemistry; vol. 120; (2016); p. 97 – 110;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 123-32-0, name is 2,5-Dimethylpyrazine, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C6H8N2

1), in 125 ml in the reaction bottle, by adding 1.08g (10mmol) 2, 5-dimethyl-pyrazine, 1.13g (4mol) FeSO4· 7H2O, by adding 30 ml of water (i.e., 3 ml/1mmol), stirring in the ice bath, then measure 0.1mol (6 ml) 98% concentrated sulfuric acid to constant pressure dropping funnel slowly dropping, the temperature change in the process of dropping the attention, to maintain the temperature of the reaction bottle too high (i.e., to control the temperature to 60 C the following can be). After concentrated sulfuric acid instillment , on a rectifier 22mmol (7.5 ml) hydrogen peroxide, PV drop instillment , and to continue the reaction in the ice bath, dripping at any time in the process of observing reaction bottle temperature change (i.e., to control the temperature to 60 C the following can be). After dripping adding 240uL (3mmol) is propionaldehyde, slowly elevated temperature so as to control the temperature to 50-60C, in the reaction 1h, 2h, 3h, 4h are respectively adding 240uL is propionaldehyde. In the reaction process and reaction conditions for TLC, reaction conditions estimated raw material, when the raw material after the reaction is complete can stop the reaction (about 6h).2), stop heating after the reaction, cooling to room temperature, with 30 ml ethyl acetate extraction, the aqueous phase (the lower) the quality of the diluted for the fraction of 20% NaOH to adjust the pH to 8, in the process the alkali adjusting full stirring, not to allow the temperature of the solution is too high (i.e., not to exceed 60 C). Then extracting with ethyl acetate three times, combined with the phase (the upper), pressure-reducing (pressure -0.08–0.10 MPa) concentrated to dry, yellow oily substance is about 1.532 g. Finally through the column chromatography the 2-ethyl -3, 6-dimethyl-pyrazine separated.As follows:The silica gel chromatography (built-in 200-300 purpose silica gel 30g), the resulting 1.532g for column chromatography yellow oily substance; for the mobile phase ethyl acetate: petroleum ether = 1:20 of the mixed solution, the total consumption of mobile phase about 500 ml; final 1.245g product—2-ethyl -3, 6-dimethyl-pyrazine (the purity is 95.6%). Yield 90.88%.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 123-32-0.

Reference:
Patent; Zhejiang University; Cheng, Jingli; Wang, Likun; Zhao, Yang; Zhao, Jinhao; (9 pag.)CN105237486; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 369638-68-6, 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. 369638-68-6, name is tert-Butyl (5-methylpyrazin-2-yl)carbamate, This compound has unique chemical properties. The synthetic route is as follows.

tert-butyl 5-methylpyrazin-2-yl carbamate (6.27 g, 30.0 mmol) was weighed and dissolved in 30 mL dichloromethane, and in an ice water bath, 20 mL trifluoroacetic acid was added slowly. It was moved to react at room temperature for 1 hour, rotate evaporated to dryness to remove the solvent, and was used for the next step directly.

The chemical industry reduces the impact on the environment during synthesis tert-Butyl (5-methylpyrazin-2-yl)carbamate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; KBP Biosciences Co., Ltd.; ZHANG, Yan; ZHANG, Min; LO, HoYin; (52 pag.)EP2781508; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 369638-68-6,Some common heterocyclic compound, 369638-68-6, name is tert-Butyl (5-methylpyrazin-2-yl)carbamate, molecular formula is C10H15N3O2, 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.

tert-butyl 5-methylpyrazin-2-yl carbamate (6.27 g, 30.0 mmol) was weighed and dissolved in 30 mL dichloromethane, and in an ice water bath, 20 mL trifluoroacetic acid was added slowly. It was moved to react at room temperature for 1 hour, rotate evaporated to dryness to remove the solvent, and was used for the next step directly.

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

Reference:
Patent; Zhang, Yan; Zhang, Min; Lo, Hoyin; US2014/303186; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 6863-73-6, A common heterocyclic compound, 6863-73-6, name is 3-Chloropyrazin-2-amine, molecular formula is C4H4ClN3, 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.

Benzyl alcohol (4.55 g, 42.15 mmol) was added under an inert atmosphere dropwise to a suspension of sodium hydride (1. 01 g, 42.13 mmol, 80%) in N-methylpyrrolidinone. Stirring of the reaction mixture was continued for 30 min. 2-Amino-3-chloropyrazine (Compound I in Scheme 1, 5.0 g, 38.6 mmol) was then added in incrememtal portions and the resultant mixture was heated at 80 C for 24 h. The reaction mixture was subsequently cooled and water (200 mL) was added. The aqueous solution was extracted with EtOAc (2 x 40 mL). The combined organic layers were washed with water (2 x 100 mL), dried (Mg04), and concentrated under reduced pressure to obtain a light brown residue. Addition of cold water to the residue, triggered crystallization of the desired product. The crystals were collected and dried over P2O5 (6.33 g, 82%). 1H-NMR (CDCl3) No. 7. 54 (d, J 3.1 Hz, 1H), 7.45-7. 32 (m, 6H), 5. 38 (s, 2H), 4. 78 (br s, 2H); MS (ESI) 202.2 ([M+H] +)

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; CARDIOME PHARMA CORPORATION; WO2005/34837; (2005); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 33332-25-1, 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. 33332-25-1 name is Methyl 5-chloropyrazine-2-carboxylate, 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.

Combine 5-CHLOROPYRAZINE-2-CARBOXYLIC acid methyl ester (626 mg, 3.64 mmol), phenylboronic acid (666 mg, 5.45 mmol), cesium fluoride (55 mg, 0.36 mmol) and NA2CO3 (964 mg, 9.09 mmol) in DMF (5 mL) and water (5 mL) with stirring. Place the hetereogeneous reaction mixture, open to the air, in an oil bath maintained at 80C. After 5 minutes of heating, add Pd (OAC) 2 (81 mg 0.36 mmol) in one portion and stir until reaction turns black. Cool the reaction to room temperature, dilute with ethyl acetate, and filter through a short plug of celite with additional ethyl acetate. Wash the organics with water, dry over MGS04, filter and evaporate. Purification by flash column chromatography yields 2-phenylpyrimidine-5-carboxylic acid methyl ester as a yellow solid. Dissolve the purified ester in THF (0.25M) and add an equal volume of 1M NAOH. Stir vigorously at room temperature for 15 hours. Upon completion, acidify the reaction with conc. HCI and extract with ethyl acetate. Evaporation of the solvent yields 63 mg (8%) of the title COMPOUND. H NMR (DMSO): 9.37 (s, 1H), 9.21 (s, 1H), 8.23-8. 21 (m, 2H), 7.57-7. 77 (m, 3H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 5-chloropyrazine-2-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; ELI LILLY AND COMPANY; WO2004/94382; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

6164-79-0, Adding a certain compound to certain chemical reactions, such as: 6164-79-0, name is Methyl 2-pyrazinecarboxylate, 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 6164-79-0.

Methyl 3-oxo-3-(pyrazin-2-yl)propanoate: To a stirred solution of sodium methoxide (25% in MeOH, 27.54 mL, 72.4 mmol, 1 eq) in 90 mL of toluene at 110 C. in a 3-neck flask attached with a mechanical stirrer, condenser and dropping funnel was added a solution of methylpyrazine-2-carboxylate (10 g, 72.4 mmol, 1 eq) in 115 mL of methyl acetate, dropwise, over a period of ?35-40 min. A yellow precipitate was formed. Stirring was continued at 110 C. for 3 hrs. The reaction was cooled and the yellow precipitate was filtered and washed with a small quantity of toluene. This solid was taken into 200 mL of saturated ammonium chloride and 400 mL of EtOAc. The aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over magnesium sulfate, filtered and evaporated to give 6.52 g (50%) of methyl 3-oxo-3-(pyrazin-2-yl)propanoate as a yellow solid.

According to the analysis of related databases, 6164-79-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Hoffmann-La Roche Inc.; Bhagirath, Niala; Brameld, Kenneth Albert; Kennedy-Smith, Joshua; US2013/90333; (2013); 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 33332-25-1 as follows. Computed Properties of C6H5ClN2O2

A solution of methyl 5-chloropyrazine-2-carboxylate (1.0 g, 5.79 mmol) and morpholine (756 mg, 8.69 mmol) in DMSO (10 mL) was added K2CO3 (2.4 g, 17.4 mmol). The mixture was heated to 100C for 4 hours and then cooled to r.t. Water (20 mL) was added and the mixture was extracted with EA (20 mLx3).The combined organic phase was washed with water (20 mL) and brine (20 mL). It was then dried over anhydrous Na2SO4 and concentrated to give the desired product as a yellow solid (850 mg) which was used directly next step. ESI-MS m/z: 224.1 [M+H]+.

According to the analysis of related databases, 33332-25-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ENANTA PHARMACEUTICALS, INC.; SHOOK, Brian, C.; KIM, In, Jong; BLAISDELL, Thomas, P.; YU, Jianming; PANARESE, Joseph; LIN, Kai; RHODIN, Michael, H.J.; McALLISTER, Nicole, V.; OR, Yat, Sun; (447 pag.)WO2019/67864; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 41110-28-5, These common heterocyclic compound, 41110-28-5, name is 3-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.

Example 1.1: Preparation of 3-methyl-pyrazine-2-carboxylic acid ethyl esterTo a solution of 3-methyl-pyrazine-2-carboxylic acid (10 g) (commercially available) and jV,7V-dimethylformamide (“DMF”) (1 drop) in dichloromethane (20 ml) at ambient temperature was added drop wise oxalyl chloride (2.57 ml). The reaction mixture was stirred at ambient temperature for 1 hour. The reaction mixture was concentrated and the residue dissolved in dichloromethane (20 ml). Triethylamine (4.04 ml) was added to this solution followed by drop wise addition of ethanol (10 ml). The reaction mixture was stirred at ambient temperature for one hour and then concentrated. The residue was purified by chromatography on silica gel (eluent: 0-10% v/v ethyl acetate in zso-hexane) to give 3- methyl-pyrazine-2-carboxylic acid ethyl ester (9.85 g). MH+ = 167, RT = 0.73 min (Method A). IH-NMR (400 MHz, CDCl3): 8.61 (d, IH), 8.54 (d, IH), 4.49 (q, 2H), 2.85 (s, 3H), 1.46 (t, 3H) ppm.

Statistics shows that 3-Methylpyrazine-2-carboxylic acid is playing an increasingly important role. we look forward to future research findings about 41110-28-5.

Reference:
Patent; SYNGENTA LIMITED; WILLETTS, Nigel, James; MULHOLLAND, Nicholas, Phillip; WORTHINGTON, Paul, Anthony; AVERY, Alaric, James; WO2010/130970; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 356783-16-9, The chemical industry reduces the impact on the environment during synthesis 356783-16-9, name is 3,6-Dichloropyrazine-2-carbonitrile, I believe this compound will play a more active role in future production and life.

To a solution of 3,6-dichloropyrazine-2-carbonitrile (1.088 g, 6.25 mmol) in toluene (12 mL) at 0 C. was added dropwise methyl hydrazine (362 muL, 6.88 mmol). Reaction mixture was stirred for 3 hours at 0 C. LCMS shows no starting material. Reaction mixture was concentrated and purified by CombiFlash (120 g Gold, 10-45% EtOAc/Hex) to give impure product. Crystallized from hot acetone/hexane to give two crops of 5-chloro-1-methyl-1H-pyrazolo[3,4-b]pyrazin-3-amine. LCMS-ESI+: calc’d for C6H7ClN5: 184.0 (M+H)+; found: 184.2 (M+H)+.

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, 3,6-Dichloropyrazine-2-carbonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Gilead Sciences, Inc.; Cai, Zhenhong R.; Guo, Hongyan; Ji, Mingzhe; Jin, Haolun; Lee, Amy; McFadden, Ryan; Mitchell, Michael L.; Munoz, Manuel; Pyun, Hyung-Jung; Xu, Lianhong; Yang, Hong; (272 pag.)US2018/118734; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem