Tag: M.W=100-200

Synthetic Route of 1286754-14-0, 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. 1286754-14-0 name is Ethyl imidazo[1,2-a]pyrazine-3-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.

To a suspension of imidazo[1,2-a]pyrazine-3-carboxylic acid ethyl ester (0.21 g) and a solution of 4 mol/L hydrogen chloride in ethyl acetate (360 muL) in ethanol (3 mL) was added 10% palladium carbon (0.080 g) at room temperature, and the mixture was stirred overnight under hydrogen atmosphere. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. To the residue were added tetrahydrofuran (3 mL), triethylamine (460 muL) and benzyloxycarbonyl chloride (250 muL), and the mixture was stirred overnight at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by aminopropyl silica gel column chromatography (eluent:ethyl acetate/n-hexane=60/40 to 85/15) to afford 5,6-dihydro-8H-imidazo[1,2-a]pyrazine-3,7-dicarboxylic acid 7-benzyl-3-ethyl ester (0.16 g). To a solution of 5,6-dihydro-8H-imidazo[1,2-a]pyrazine-3,7-dicarboxylic acid 7-benzyl-3-ethyl ester (0.16 g) in ethanol (3 mL) was added an aqueous solution of 2 mol/L sodium hydroxide (315 muL). The mixture was stirred for 30 minutes under reflux, and allowed to cool to room temperature. To the mixture was added 2 mol/L hydrochloric acid (315 muL), and concentrated under reduced pressure to afford 5,6-dihydro-8H-imidazo[1,2-a]pyrazine-3,7-dicarboxylic acid 7-benzyl ester (0.146 g). To a solution of (R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride (0.108 g) and triethylamine (0.049 g) in methanol (2 mL) was added benzaldehyde (0.052 g), and the mixture was stirred for 30 minutes at 65 C. The reaction mixture was allowed to cool to room temperature. To the mixture were added 5,6-dihydro-8H-imidazo[1,2-a]pyrazine-3,7-dicarboxylic acid 7-benzyl ester (0.146 g) and 4-phenylcyclohexen-1-ylisocyanide (0.089 g). The mixture was stirred overnight at 65 C., then allowed to cool to room temperature, and concentrated under reduced pressure. To the obtained residue were added tetrahydrofuran (4 mL), water (100 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (500 muL), and the mixture was stirred for 30 minutes at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by aminopropyl silica gel column chromatography (eluent: methanol/ethyl acetate=4/96) to afford 3-{N–[(R)-carbamoylphenylmethyl]-N–[(R)-6-chloro-4-fluoroindan-1-yl]car- bamoyl}-5,6-dihydro-8H-imidazo[1,2-a]pyrazine-7-carboxylic acid benzyl ester (0.038 g) as a low polarity diastereomer. To a suspension of 3-{N–[(R)-carbamoylphenylmethyl]-N–[(R)-6-chloro-4-fluoroindan-1-yl]car- bamoyl}-5,6-dihydro-8H-imidazo[1,2-a]pyrazine-7-carboxylic acid benzyl ester (0.038 g) in tetrahydrofuran (3 mL) was added 10% palladium carbon (0.020 g) at room temperature, and the mixture was stirred for a day under hydrogen atmosphere. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by aminopropyl silica gel column chromatography (eluent: methanol/ethyl acetate=0/100 to 20/80) to afford the title compound (0.23 g).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl imidazo[1,2-a]pyrazine-3-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; Kissei Pharmaceutical Co., Ltd; Hirasawa, Hideaki; Kawamura, Naohiro; Kobayashi, Junichi; (160 pag.)CN105263901; (2016); 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. 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2-Bromo-5H-pyrrolo[2,3-b]pyrazine

Step 1. 2-Bromo-7-iodo-5H-pyrrolo[2,3-b]pyrazine. To a solution of 2-bromo-5H-pyrrolo[2,3-b]pyrazine (8 g, 40.4 mmol) in DMF (160 mL) was added N-iodosuccinimide (11.8 g, 3.6 mmol) at room temperature, and stirred for 1 h. TLC (Petroleum ether: EtOAc, 2:1) indicated the reaction was completed. reaction mixture was diluted with water (500 mL), and extracted with EtOAc (300 mL×3). The combined organic layers were washed with brine, and dried over Na2SO4. After filtration, the solvent was removed under reduced pressure to give 2-bromo-7-iodo-5H-pyrrolo[2,3-b]pyrazine (26.1 g, 100%) as brown solid (containing some DMF).

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 875781-43-4.

Reference:
Patent; Thorarensen, Atli; Brown, Matthew Frank; Casimiro-Garcia, Agustin; Che, Ye; Coe, Jotham Wadsworth; Flanagan, Mark Edward; Gilbert, Adam Matthew; Hayward, Matthew Merrill; Langille, Jonathan David; Montgomery, Justin Ian; Telliez, Jean-Baptiste; Unwalla, Rayomand Jal; US2015/158864; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 88625-24-5, A common heterocyclic compound, 88625-24-5, name is 5-Chloropyrazine-2-carbaldehyde, molecular formula is C5H3ClN2O, 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.

3,3-Difluoroazetidine hydrochloride [CAS RN: 288315-03-7] (436 mg, 3.37 mmol,1.6 eq), 5-chloropyrazine-2-carbaldehyde [CAS RN: 88625-24-5] (300 mg,2.11 mmol, 1.0 eq) and sodium triacetoxyborohydride (1.47 g, 6.74 mmol,3.2 eq) were suspended in 20 mL 1,2-dichloroethane. Then, triethylamine (0.59mL, 4.21 mmol, 2.0 eq) was added and the reaction mixture was stirred at rtovernight. Then, water was added and the resulting phases were separated by the use of a Whatman filter. The volatile components of the organic phase were removed in vacuo and the crude material was purified via preparative MPLC (Biotage Isolera; 25 g SNAP cartridge: hexane/ethyl acetate 9/1 -> hexane/ethyl acetate 1/1) to give 330mg (70% yield of theory) of the title compound.UPLC-MS (Method 1): R = 0.65 mm; MS (EI0): m/z = 220 [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; BAYER PHARMA AKTIENGESELLSCHAFT; BAeRFACKER, Lars; SIEMEISTER, Gerhard; HEINRICH, Tobias; PRECHTL, Stefan; STOeCKIGT, Detlef; ROTTMANN, Antje; WO2015/113927; (2015); A1;,
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., Quality Control of 2,5-Dimethylpyrazine

A method for preparing 5-methylpyrazine-2-carboxylic acid by catalytic oxidation, firstly, diatomaceous earth, manganese chloride, sodium tungstate,Cobalt nitrate and distilled water were added to the reactor at the following element mass ratio: diatomaceous earth: Mn:W:Co:H2O=1:0.09:0.08:0.14:50,Magnetically stirring at room temperature to make it dispersed and uniformly adsorbed, and then removing water by evaporation.Adding a liquid silica sol with a total mass of 5% of the solid sample and kneading it into a small granular sample of 1-2 mm.The mixture was placed in a muffle furnace and calcined in an air atmosphere at 600 C for 5 hours to obtain Mn-W-Co/diatomaceous earth-supported catalyst particles.10 g of Mn-W-Co/diatomaceous earth catalyst particles were packed into a fixed bed microreactor reaction tube, and the reactor was heated to 330 C.The reaction raw material 2,5-dimethylpyrazine was introduced into a fixed bed reaction tube by bubbling with high-temperature steam at 10 ml/min.Oxygen is introduced into the reaction tube separately at 20 ml/min to cause catalytic oxidation of 2,5-dimethylpyrazine in the catalytic bed.The 5-methylpyrazine-2-carboxylic acid is produced and taken out of the reaction tube by water vapor, condensed, crystallized, and collected.Analysis of 5-methylpyrazine-2-carboxylic acid by gas chromatographyThe yield was 75.6%.

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; Lanzhou University; Dong Zhengping; (6 pag.)CN109369544; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 22047-25-2, A common heterocyclic compound, 22047-25-2, name is Acetylpyrazine, molecular formula is C6H6N2O, 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.

Preparation 8; 1-Pyrazin-2-yl-ethyl Amine; The synthetic procedure used in this preparation is outlined below in Scheme J. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dichloromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75%. MS (M+H)=124.

The synthetic route of 22047-25-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Roche Palo Alto LLC; US2009/163502; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 13924-95-3, name is Methyl 5-hydroxypyrazine-2-carboxylate, 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. Application In Synthesis of Methyl 5-hydroxypyrazine-2-carboxylate

Step 1 5-Bromo-pyrazine-2-carboxylic acid methyl ester A solution of 5-hydroxy-pyrazine-2-carboxylic acid methyl ester (2.56 g, 16.61 mmol) in phosphorous oxybromide 9.9 g, 34.9 mmol) were heated at 90 C. for 70 mins. The reaction was allowed to cool and the resulting solid carefully dissolved in methanol and then the solvent was evaporated in vacuo. The residue was partitioned between EtOAc and sat. NaHCO3 and the organic extracts were washed with brine, dried (Na2 SO4) and evaporated in vacuo. The residue was chromatographed (silica gel, EtOAc:Hexanes 40:60) to afford the title compound. 1 H NMR (400 MHz, CDCl3) delta 9.06 (d, J=1.4 Hz,1H), 8.80 (d, J=1.4 Hz,1H), and 4.04 (s, 3H) ppm.

The synthetic route of Methyl 5-hydroxypyrazine-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Merck & Co., Inc.; US5939439; (1999); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 69816-38-2, name is 5-(Trifluoromethyl)pyrazin-2-amine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 5-(Trifluoromethyl)pyrazin-2-amine

Heat a mixture of 5-chloro-2- (3-methylpyridin-2-yl)- [1, 8] naphthyridine (51 mg, 0.2 MMOL), 2-AMINO-5-TRIFLUOROMETHYLPYRAZINE (42.0 mg, 0. 25 MMOL), xantphos (11.6 mg, 0.02 mmol), Pd2 (dba) 3 (18.3 mg, 0.02 mmol) and Cs2CO3 (130 mg, 0.4 mmol) in dioxane (2.0 mL) at 100C for 20 HOURS. COOL the mixture, concentrate under vacuum, dilute with EtOAc/ water (5.0 mL each), filter through celite, wash celite with EtOAc (2 x 5 mL) and dry the combined organic layers with MGS04. Filter the dried extract and concentrate under vacuum to afford the crude product. Purify by preparative TLC using 2% MEOH/ETOAC as eluent to afford the title compound as a yellow SOLID. H NMR (400 MHZ, DMSO-D6) 8 10.6 (s, 1H), 9.04 (d, 1H, J=2.1 Hz), 9.0 (s, LH), 8.77 (s, 2H), 8.59 (d, 1H, J=1.6 Hz), 8.4 (s, 1H), 8.20 (d, 1H, J=2. 2 Hz), 7. 81 (d, IH, J=L. 9 Hz), 7.42 (dd, 1H), 2.65 (s, 3H). MS = 383. 11 (M+H).

The synthetic route of 69816-38-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NEUROGEN CORPORATION; WO2005/7652; (2005); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, 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. Computed Properties of C6H6N2O2

Step F: N-((1S,3S,4R)-3-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-4-methylcyclopentyl)-5-methylpyrazine-2-carboxamide 5-Methylpyrazine-2-carboxylic acid (0.135 g, 0.98 mmol) was dissolved in DMF (3 mL). HATU (0.447 g, 1.17 mmol) was added and the mixture stirred at ambient temperature for about 1 min. TEA (0.6 mL, 4.30 mmol) and (1S,3S,4R)-3-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-4-methylcyclopentylamine (0.250 g, 0.98 mmol) were added and the resulting mixture was stirred at ambient temperature for about 1 h. The mixture was diluted with DCM (10 mL) and washed with a saturated aqueous solution of NaHCO3 (5 mL). The organic layer was collected, dried over MgSO4, filtered and evaporated. The resulting solid was sequentially triturated with Et2O and MeOH. The resulting solid was filtered. The filtrate was evaporated to dryness. The solid was triturated with DCM/DMF (20/1 by volume) to give a white solid that was combined with solid recovered from the Et2O/MeOH filtrate. The combined solids were triturated with EtOAc, filtered and dried to give N-((1S,3S,4R)-3-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-4-methylcyclopentyl)-5-methylpyrazine-2-carboxamide (0.164 g, 44%); LC/MS (Table 1, Method a) Rt=1.7 min; MS m/z: 376 (M+H)+. Jak3 IC50=C

The synthetic route of 5521-55-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ABBVIE INC.; Wishart, Neil; Bonafoux, Dominique F.; Frank, Kristine E.; Hobson, Adrian D.; Konopacki, Donald B.; Martinez, Gloria Y.; Wang, Lu; US2013/72470; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 4774-14-5,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.

Preparation of tert-butyl (1-(6-chloropyrazin-2-yl)azetidin-3-yl)carbamate (LXV) is depicted below in Scheme 13. Step 1 (0850) To a solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (LXIII) (2 g, 9.58 mmol) in dry DMF (19.2 mL) was added DIPEA (8.37 ml, 47.9 mmol). To this mixture was added 2,6-dichloropyrazine (LXIV) (1.428 g, 9.58 mmol) and the reaction was stirred at 95 C. for 3 hours. The reaction was quenched with water (20 mL) and extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (40 g) (100% hexanes?hexanes:EtOAc 1:1) to yield tert-butyl (1-(6-chloropyrazin-2-yl)azetidin-3-yl)carbamate (LXV) (2.2882 g, 8.04 mmol, 84% yield) as a white solid. ESIMS found for C12H17ClN4O2 m/z 285.1 (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 2,6-Dichloropyrazine, its application will become more common.

Reference:
Patent; Samumed, LLC; KC, Sunil Kumar; Wallace, David Mark; Cao, Jianguo; Chiruta, Chandramouli; Hood, John; (264 pag.)US2016/68551; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 69214-33-1, name is 8-Chloroimidazo[1,2-a]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. Formula: C6H4ClN3

8-chloroimidazo [1,2-a] pyrazine (1.07 g, 7 mmol) was dissolved in 15 mL glacial acetic acid, and liquid bromine (1.12 g, 7 mmol) was slowly added dropwise under an ice bath.Remove the ice bath after the addition and stir overnight at room temperature.TLC showed that the reaction was complete. Add 30 mL of saturated sodium sulfite solution and extract with ethyl acetate (30 mL * 3).The organic phases were combined and washed with 20 mL of saturated brine.Dry over anhydrous sodium sulfate, concentrate,Separation through a silica gel column gave 1.33 g of a pale yellow solid with a yield of 82%.

The synthetic route of 8-Chloroimidazo[1,2-a]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shenzhen Tajirui Bio-pharmaceutical Co., Ltd.; Wang Yihan; Xing Qingfeng; Ai Yixin; (85 pag.)CN110272426; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem