Tag: M.W=100-200

Adding a certain compound to certain chemical reactions, such as: 38557-72-1, name is 2-Chloro-3,5-dimethylpyrazine, 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 38557-72-1, name: 2-Chloro-3,5-dimethylpyrazine

Step 1: Synthesis of 3,5-Dimethyl-2-(4-naphthalen-1-yl-phenyl)pyrazine (abbreviation: Hdm1nppr)First, into a recovery flask equipped with a reflux pipe were placed 0.74 g of 2-chloro-3,5-dimethylpyrazine, 1.29 g of 4-(1-naphthyl)phenylboronic acid, 0.55 g of sodium carbonate, 0.024 g of bis(triphenylphosphine)palladium(II) dichloride (abbreviation: Pd(PPh3)2Cl2), 10 mL of water, and 10 mL of acetonitrile, and the air in the flask was replaced with argon. This reaction container was irradiated with microwaves (2.45 GHz, 100 W) for 15 minutes, so that heating was performed. Then, the reaction container was cooled to 50 C. or less. Water was added to the reaction solution, and the organic layer was extracted with dichloromethane. The obtained organic layer was washed with water and dried with magnesium sulfate. The solution which had been dried was filtered. The solvent of this solution was distilled, and recrystallized using ethyl acetate, whereby Hdm1nppr, which is the pyrazine derivative to be produced, was obtained (as a white powder in 50% yield). Note that the microwave irradiation was performed using a microwave synthesis system (Discover, manufactured by CEM Corporation). The synthesis scheme of Step 1 is illustrated in the following (a-1).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-3,5-dimethylpyrazine, and friends who are interested can also refer to it.

Reference:
Patent; Semiconductor Energy Laboratory Co., Ltd.; US2011/245495; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 14508-49-7, These common heterocyclic compound, 14508-49-7, name is 2-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.

A mixture of 2-chloropyrazine (28.6 g, 0.25 mol) and thiourea (19 g, 0.25 mol) were added into 200 mL ethanol. The mixture was refluxed for 3 h under vigorous stir in a 500 mL three-necked flask. After alcohol was removed by the evaporation, diluted sodium hydroxide solution (30 wt%, 300 g) was gradually added into the flask. The mixture was heated with reflux for another 5 h and a large amount of ammonia was released. After cooled to ambient temperature, the pH of the solution was adjusted to 6.5 by adding quantitatively diluted hydrochloric acid. Extraction was carried out with dichloromethane. Dichloromethane layerwas collected and washed with water for several times. Yellow powder was obtained through evaporation in 68% (wt) yield. The whole synthesis is illustrated in Scheme 1. The elemental analysisresult for C4HN2S in mass %: C, 35.82; H, 2.25; N, 20.89. Experiment:C, 36.13; H, 2.01; N, 20.56.

Statistics shows that 2-Chloropyrazine is playing an increasingly important role. we look forward to future research findings about 14508-49-7.

Reference:
Article; Wu, Yining; Wu, Xuepeng; Fang, Sisi; Yang, Shuai; Li, Weitao; Wang, Huan; Yu, Xiaoxi; Polyhedron; vol. 122; (2017); p. 155 – 160;,
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.

alpha-Bromo diethyl acetal (51.6 mL, 332.7 mmol, 2.5 eq) was added to a solution of 7.7 mL HBr (conc.) and 80 mL of H2O. The reaction was heated at reflux for 1 h. The reaction was cooled and extracted 2× with Et2O (200 mL). The Et2O extracts were combined, washed with brine, and dried over Na2SO4 before being concentrated. The material was not left on the rotavap for an extended time or put under high vacuum. The oily residue was mixed with DME (200 mL) and the 2-amino-3-chloropyrazine (2, 17.240 g, 133.1 mmol) was added. HBr conc. (1-1.5 mL) was added and the reaction was heated at reflux. The reaction is heterogeneous reaction mixture, becomes homogenous after 10-15 minutes. After approximately 30 minutes a precipitate begins to form. After 1 hour at reflux the black reaction was cooled to room temperature, filtered, and washed with Et2O (4×, 75 mL) to give compound 101 1H NMR (DMSO-d6, 400 MHz) 8.70 (d, J=2.0 Hz, 1H), 8.32 (s, 1H), 7.93 (s, 1H), 7.79 (d, J=3.0 Hz, 1H). LC/MS shows a mixture of two products (one product by LC and two by MS). By MS there is a mass for XCl (major) MH+=154 (m/z) and one for XBr (minor) MH+ 198 (m/z). This mixture gave the product in approximately 90% yield as the HBr salt.

The synthetic route of 6863-73-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Schering Corporation; US2007/105864; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 4858-85-9, A common heterocyclic compound, 4858-85-9, name is 2,3-Dichloropyrazine, molecular formula is C4H2Cl2N2, 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.

Starting material A-1 (15 g; 100.68 mmol) and hydrazine hydrate 65 % (15.509 ml201.37 mmol) are dissolved in 45 ml_ ethanol and stirred for 1 h at 80 C. While cooling down, a precipitate is formed. It is slurred up with a small amount of water and filtered off. It is washed with water and then dried to afford the product. Yield: 93 % (13.6 g; 94.07mmol) (0279) HPLC-MS: (M+H)+ = 145/147; tRet = 0.34 min; method FECB5

The synthetic route of 4858-85-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; TONTSCH-GRUNT, Ulrike; BAUM, Anke; RUDOLPH, Dorothea Ingrid; (85 pag.)WO2019/145410; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

313339-92-3, name is 3,5-Dichloropyrazine-2-carbonitrile, 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. SDS of cas: 313339-92-3

(4-tert-Butoxycarbonyl-aminophenyl)boronic acid pinacol ester (8.26 g) was added to a reaction vessel containing a magnetic stirring bar together with 3,5-dichloro- pyrazine-2-carbonitrile (5.0 g), 1,1 ?-bis(diphenylphosphino)ferrocene-palladium(II) dichloride (1.68 g) and cesium carbonate (28.1 g), followed by 100 ml dioxane and 10 ml water, and the mixture heated to 100 00 under stirring. After 1 h the reaction mixture was cooled to RT and quenched with a saturated aqueous sodium bicarbonate solution (100 ml) and extracted with EtOAc (3 x 200 ml). The combined organic phases were dried over sodium sulfate, filtered and evaporated to afford the crude product as a brown oil which was purified by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent. The obtained product was recrystallized from methyl tert-butyl ether to afford [4-(6-chloro-5-cyano-pyrazin-2-yl)-phenyl]-carbamic acid tert-butyl ester as a pale yellow solid after drying under vacuum. Yield: 6.92 g (73%).

The synthetic route of 313339-92-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SANOFI; NAZARE, Marc; HALLAND, Nis; SCHMIDT, Friedemann; WEISS, Tilo; DIETZ, Uwe; HOFMEISTER, Armin; WO2013/41502; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 36070-79-8, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 36070-79-8, name is 6-Chloropyrazine-2-carboxamide belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 6-chloropyrazine-2-carboxamide (75 mg, 0.47 mmol) and (2- (methylthio)benzo[djthiazol-6-yl)methanamine (50 mg, 0.24 mmol) in DMA (475 .il) was added DIEA (46 pi, 0.26 mmol) and the resulting mixture was stirred at 120 C for 2 h. The mixture was concentrated. The residue was purified via silica gel chromatography (0 – 10 % MeOH in DCM with 0.2% NH4OH) to give the title compound (43 mg, 55%) as a tan solid. MS (ES+) C,4H,3N5052 requires: 331, found: 332 [M+Hf?. ?H NMR (500 MHz, DMSO-d6)oe 8.22 (s, 1H), 8.13 (s, 1H), 8.02 (s, 1H), 7.94 – 7.89 (m, 2H), 7.80 (d, J= 8.4 Hz, 1H), 7.61 (s, 1H), 7.48 (d, J= 9.5 Hz, 1H), 4.72 (d, J 5.8 Hz, 2H), 2.78 (s, 3H)

The synthetic route of 6-Chloropyrazine-2-carboxamide has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TESARO, INC.; JONES, Philip; CZAKO, Barbara; BURKE, Jason P.; CROSS, Jason; LEONARD, Paul Graham; (208 pag.)WO2018/81276; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 870787-06-7,Some common heterocyclic compound, 870787-06-7, name is 3-(Trifluoromethyl)pyrazine-2-carboxylic acid, molecular formula is C6H3F3N2O2, 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.

A compound (2 mmol) represented by the formula (2-1) was added to a 100 mL round bottom flask.EDCI (2.4 mmol), HOBt (2.4 mmol) and 10 mL of DMF were reacted at 25 C for 1 h.Then, the compound represented by formula (2-21) or formula (2-22)(2.4 mmol) was added to the above solution,Reaction at 25 C for 24 h,After removing the solvent, column chromatography gave the desired product (yield of the desired product as a one-step yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-(Trifluoromethyl)pyrazine-2-carboxylic acid, its application will become more common.

Reference:
Patent; Central China Normal University; Yang Guangfu; Li Hua; Xiong Li; (10 pag.)CN109666004; (2019); A;,
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. 41110-33-2, name is Methyl 5-methylpyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of Methyl 5-methylpyrazine-2-carboxylate

5-Methyl-pyrazine-2-carboxylic acid methyl ester (1.60 g, 10.5 mmol; Macdonald, S. J. F. et al. J.Med.Chem. 2002, 45(18):3878-3890.), N-bromosuccinimide (5.62 g, 31.6 mmol), and dibenzoyl peroxide (0.255 g, 1.05 mmol) were dissolved in CCl4 (80 mL). The mixture was heated at reflux for 18 h. The reaction mixture was cooled and washed with 10% aq. Na2SO3 (2×20 mL) and H2O (1×30 mL). The organic phase was dried over Na2SO4, filtered, and concentrated to yield a brown oily crude material (2.41 g). The crude product was purified (SiO2: 0-20% ethyl acetate/hexanes) to give the title compound (1.00 g, 31%).

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 41110-33-2.

Reference:
Patent; Carruthers, Nicholas I.; Shah, Chandravadan R.; Swanson, Devin M.; US2005/222151; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 939412-86-9, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

(2R,5R)-tert-butyl 5-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(hydroxymethyl) morpholine-4-carboxylate (2g, 4.12 mmol) was dissolved in 100 mL CH2Cl2and cooled to 0 C. TEMPO(0.13 g, 0.82 mmol) was added, followed by (diacetoxyiodo)benzene (2.65 g, 8.24 mmol). The ice bath was removed, and the reaction was allowed to warm to room temperature and stirred overnight. The mixture was diluted with 200 mL ethyl acetate and washed with 10% Na2S203, aq. satd. NaHC03, and brine. The organic phase was dried with Na2S04, filtered and concentrated to give (2R,5R)-4-(tert- butoxycarbonyl)-5 -(((tert-butyl diphenylsilyl)oxy)methyl)morpholine-2-carboxylic acid (1.36g, 66%). LCMS: [M-H]+:498.23 Ret. time= 1.33 min, LC-MS method E). Used as such for the next step without any further purification. (2R,5R)-4-(tert-butoxycarbonyl)-5-(((tert- butyldiphenylsilyl)oxy)methyl)morpholine-2-carboxylic acid (1.5g, 3.0 mmol) and (3- chloropyrazin-2-yl)methanamine. HC1 salt (0.54g, 3.0 mmol) were dissolved in DMF 100 mL. To the reaction mixture was added Et3N (0.76g, 6.0 mmol) followed by slow addition of HATU (1.37g, 3.6 mmol) at 0 C. The reaction was stirred at rt for 1 day under a stream of nitrogen and then quenched with sat. NaHC03 (100 mL) and extracted with EtOAc(2xl50 mL). The combined organic layer was washed with water(200 mL) , brine(200mL), dried over anhydrous Na2S04, filtered, and evaporated. The crude residue was subjected to column purification using 20-50%) EtO Ac/Hex. to give (2R,5R)-tert-butyl 5-(((tert-butyldiphenylsilyl)oxy) methyl)-2-(((3-chloropyrazin- 2-yl)methyl)carbamoyl)morpholine-4-carboxylate (0.86g, 46%). LCMS: [M-Boc +H]+:525.25 Ret. time= 2.74 min, LC-MS method E).

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-Chloropyrazin-2-yl)methanamine hydrochloride, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK SHARP & DOHME CORP.; WU, Hao; KIM, Ronald M.; LIU, Jian; GAO, Xiaolei; BOGA, Sobhana Babu; GUIADEEN, Deodialsingh; LIU, Shilan; YANG, Chundao; WANG, Hongjian; WO2014/113932; (2014); 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 4774-14-5 as follows. Recommanded Product: 4774-14-5

EXAMPLE 5 2-amino-6-chloropyrazine 120 ml of water, 20.8 ml (0.31 mol, 4.6 eq) of an aqueous 28% ammonia solution and 10 g (0.067 mol, 1 eq) of 2,6-dichloropyrazine were successively added to an autoclave reactor. The autoclave was sealed and the mixture heated at 140 C. for 3 h, then left at room temperature for 60 h. The mixture was filtered, the precipitate washed with water, then vacuum dried. The reaction produced 5.4 g of a fine powder (yield: 63%). 1H NMR (CDCl3) delta (ppm): 7.88 (s, 1H, CH); 7.84 (s, 1H, CH); 4.68 (m, 2H, NH2). HPLC: t=1.07 min MS: 130 (MH+) HPLC purity: 100%

According to the analysis of related databases, 4774-14-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Maillet, Magali; Saniere, Laurent; Nicolai, Eric; Potin, Dominique; Langlois, Michel; US2005/267126; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem