Month: June 2021

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. Recommanded Product: 69214-33-1

A cooled (0C) suspension of 8-chloroimidazo [1, 2-A] PYRAZINE (18.6 g, 0.12 mol) and sodium acetate (29.8 g, 0.36 mol) in methanol (125 ml, pre-saturated with solid potassium bromide) was treated with bromine (6.5 ml, 0.13 mol) added dropwise over 5 min. After stirring for 10 min thin-layer chromatography indicated no starting material. Solid sodium sulphite (15.3 g, 0.12 mol) was then added to the slurry and stirring continued for 10 min. The mixture was then treated with saturated aqueous sodium hydrogencarbonate (650 ml) added in portions. This mixture was extracted with dichloromethane (2 x 350 ml). The organics were combined, dried over anhydrous magnesium sulphate, filtered and concentrated to afford 3-bromo-8-chloroimidazo [1, 2-A] PYRAZINE as a cream- coloured solid:

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

Reference:
Patent; MERCK SHARP & DOHME LIMITED; WO2004/41826; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 912773-24-1, 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 912773-24-1 as follows.

General procedure: In a 1000ml three-necked flask, equipped with mechanical stirring, Ar gas protection, adding 3-phenyl-6-chloroimidazo [1,2-a] pyrimidine (7.16 g (molecular weight: 229, 0.030 mol), p-bromophenyl boronic acid pinacol ester 9.1 g (molecular weight: 282, 0.032 mol), catalyst Pd (PPh3) 4 was used in an amount of 1.8 g (molecular weight 1154, 0.001556 mol), 120 ml of a sodium carbonate aqueous solution (2M), 300 ml of toluene and 150 ml of ethanol. Stirring reflux, with TLC monitoring reaction, reaction 3.5hs after the reaction is complete. Cooled, separated, evaporated to dryness, using column chromatography The eluent was eluted with 1: 3 ethyl acetate: petroleum ether to give 9.0 g of a pale yellow solid having a purity of 97.0% and a yield of 83.2%. The synthesis step was the same as the fourth step in Example 1,Except that 3-phenyl-6-chloroimidazo[1,2, a]pyrimidine was added Substituted with 6-bromoimidazo [1,2-A]pyrazine,(3-phenylcarbazole-9-yl) -6,6,12,12-tetramethyl-6,12-dihydroindeno [1,2-b ] Fluorene-2-boronic acid pinacol ester instead of raw materials, other raw materials and process unchanged, Compound 29 was obtained.

According to the analysis of related databases, 912773-24-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Gu’an Dingcai Technology Co., Ltd.; Li Yinkui; Tang Jinming; Fan Hongtao; (40 pag.)CN104650089; (2017); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 113305-94-5,Some common heterocyclic compound, 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, molecular formula is C5H4N4, 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 1; 5-Isothiocyanatopyrazine-2-carbonitrile; A solution of thiophosgene (1.86 g, 15 mmol) in THF (4 mL) is added dropwise to a solution of 5-aminopyrazine-2-carbonitrile (1.20 g, 10 mmol) and pyridine (2 mL) in CH2CI2 (200 mL) and THF (25 mL) at room temperature. The reaction mixture is stirred at room temperature for 3 h. The mixture is concentrated and the crude product is diluted with ethyl acetate, filtered and concentrated to give the title compound.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Aminopyrazine-2-carbonitrile, its application will become more common.

Reference:
Patent; ELI LILLY AND COMPANY; FAROUZ, Francine, S.; HOLCOMB, Ryan, Coatsworth; KASAR, Ramesh; MYERS, Steven, Scott; WO2010/77758; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 1379338-74-5, A common heterocyclic compound, 1379338-74-5, name is 5,7-Dichloropyrido[3,4-b]pyrazine, molecular formula is C7H3Cl2N3, 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.

Intermediate 32: 1,1-Dimethylethyl {4-[(7-chloropyrido[3,4-b]pyrazin-5-yl)amino]butyl}carbamate To 5,7-dichloropyrido[3,4-b]pyrazine (650 mg, 3.25 mmol) was added 1,1-dimethylethyl (4-aminobutyl)carbamate (0.622 ml, 3.25 mmol) (Fluka) and diisopropylethylamine (0.851 ml, 4.87 mmol). To the mixture was added N-methyl-2-pyrrolidone (NMP) (10 ml). The microwave vial was sealed and heated to 130 C. for 30 min. The reaction mixture was partitioned between water (70 ml) and ethyl acetate (70 ml) and then separated. The aqueous layer was extracted with ethyl acetate (2*50 ml). The combined organics were passed through a phase separation cartridge and reduced in vacuo. The residue was dissolved in DCM and loaded onto a silica cartridge (50 g) and purified via SP4 using a 15-75% EtOAc in cyclohexane gradient. The appropriate fractions were combined and concentrated to give the title compound as a yellow film (1.01 g). LCMS (Method C): Rt=1.11 min, MH+=352.0

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; GLAXO GROUP LIMITED; Atkinson, Francis Louis; Atkinson, Stephen John; Barker, Michael David; Douault, Clement; Garton, Neil Stuart; Liddle, John; Patel, Vipulkumar Kantibhai; Preston, Alexander G.; Shipley, Tracy Jane; Wilson, David Matthew; Watson, Robert J.; US2014/5188; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 5521-58-4, name is 5-Methylpyrazin-2-amine, molecular formula is C5H7N3, 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: C5H7N3

a) 2-Bromo-N-(5-methyl-pyrazin-2-yl)-acetamide To a mixture of 5-methyl-pyrazin-2-ylamine and cesium carbonate (11.2 g) dissolved in dry DMF (30 mL) was added by dropwise addition bromoacetylbromide (2.89 g) and the mixture stirred at rt for 2 hours. Water (200 mL) was added and the mixture extracted with ethyl acetate (2*100 mL) and dried over magnesium sulfate. Concentration of the extract to ~50 mL and addition of isohexane (100 mL) gave the sub-titled compound as a solid (1.64 g). 1H NMR (400 MHz, DMSO-D6) delta 11.06 (1H, s), 9.17 (1H, s), 8.31 (1H, d), 4.16 (2H, s), 2.46 (3H, s).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5521-58-4, its application will become more common.

Reference:
Patent; Bull, Richard James; Skidmore, Elizabeth Anne; Ford, Rhonan Lee; Mather, Andrew Nigel; Mete, Antonio; US2011/172237; (2011); 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 762240-92-6 as follows. name: 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride

At room temperature, compound I22.8g (100mmol), bromoacetyl chloride 31.2g (200mmol) and cesium carbonate 65.2g (200mmol) were added to the flask in 100mL DMF and stirred for 3h at room temperature; after the reaction was completed, ethyl acetate was extracted The organic phase was concentrated, washed with water, and then recrystallized from ethanol, and dried to obtain 28.4 g of compound II in a yield of 91%.

According to the analysis of related databases, 762240-92-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Nanjing Qike Pharmaceutical Co., Ltd.; Yang Bo; Chen Yao; (11 pag.)CN110577542; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 313339-92-3, The chemical industry reduces the impact on the environment during synthesis 313339-92-3, name is 3,5-Dichloropyrazine-2-carbonitrile, I believe this compound will play a more active role in future production and life.

11501] Commercial (4aR,8aR)-decahydro-1 ,5-naphthyri- dine (423, 120 mg, 0.86 mmol) was dissolved in 2 mE NMP. To it were added DIEA (150 pL, 0.86 mmol) and then 3,5- dichioropyrazine-2-cabonitrile (150 mg, 0.86 mmol). The mixture was stirred at RT for 1 .5 hour, and to it were added DIEA (450 pL, 2.58 mmol) and dimethylcarbamoyl chloride (240 pL, 2.58 mmol). The mixture was stirred at RT for overnight. It was diluted with 100 mE EtOAc, washed with water x2, dried, concentrated in vacuo, and subjected to silica flash column using 0 to 3% MeOR in DCM to isolate (4aR, 8aR)-5-(6-chioro-5-cyanopyrazin-2-yl)-N,N-dimethyloc- tahydro- 1 ,5-naphthyridine- 1 (2H)-carboxamide (424, 56 mg, 19%). It was mixed with 4-(1 -cyclopentylpiperidin-4-yl) aniline hydrochloride (304) (90 mg, 0.32 mmol), fine-powder cesium carbonate (210 mg, 0.64 mmol), Pd(OAc)2(11 mg, 0.05 mmol), I3INAP (31 mg, 0.05 mmol) in 15 mE dioxane. The mixture was degas sed with nitrogen stream for 3 mM It was then stirred in 115C. bath in nitrogen atmosphere for 1.5 hout The mixture was cooled to RT, diluted with 100 mE EtOAc, and filtered. The filtrate was concentrated in vacuo and subjected to silica flash column using 0 to 11% MeOR in DCM to isolate (4aR,8aR)-5-(5-cyano-6-(4-(1 -cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-N,N-dimethy- loctahydro-1 ,5-naphthyridine- 1 (2H)-carboxamide (425). It was dissolved in 10 mE MeOR and 2 mE DM50. To it were added one NaOH solid bead (about 100 mg), Et3N (60 IL) and then 0.5 mE 30% H202. The mixture was stirred at RT for 30 mM, diluted with 10 mE MeCN, stirred for 5 mM, and concentrated, acidified with 0.3 mE TFA, and subjected to reverse phase prep HPEC using 5 mM HC1 (aq) and neat MeCN as mobile phases to isolate (4aR,8aR)-5-(5-carbam- oyl-6-(4-(1 -cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-N,N-dimethyloctahydro-1 ,5-naphthyridine-1 (2H)-carboxamide (426) as HC1 salt (23 mg). EC-MS (ESI):mlz (M+1) 575.8. UV: X=269, 276, 305, 335, 372 nm.

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, 3,5-Dichloropyrazine-2-carbonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JIA, Zhaozhong J.; CHEN, Wei; THOMAS, William D.; US2015/158865; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 762240-92-6, A common heterocyclic compound, 762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, molecular formula is C6H8ClF3N4, 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 the 1 OOgm(3R)-3- [(1,1 -dimethyl ethoxy carbonyl)amino}-4-(2,4,5-trifluorophenyl butanoic acid charged 700m1 methylenedichioride and 67gm triethylamineandstirred for 10 minutes.Added 68gmNN?-Dicyclohexylcarbodiimide, 44.6 gm of anhydrous 1 – hydroxylbenzotriazole and maintained for about 10-20 minutes.Added75.5gm 3- trifluromentyl 5,6,7,8-tetrahydro (1 ,2,4) triazolo[4,3-a] pyrazineHCl and heated to 25- 30C and maintained for 4 hours. After completion of reaction,filtered the reaction mass and filtrate was washed with 2x350m1 2.5%sodium bicarbonate solutionandwashed with 2x500m1 of water.MDC layer was taken without purification and Cooled to 0-10C.400m1 1 6%Methanolic HCI added and raised the temperature to 25-30C and Stirred for 4 hours.After completion of the reaction added 1000m1 water and separatedlayers.ExtractedtheMDClayer with 2x300m1 DM water.Aqueous layer was washed with 300m1 MDC and pH of the aqueous layer was adjusted to 10-1 1%with 1 0%sodium hydroxide solution. 1 000m1 MDC charged and Stirred for I 0mm. The organic layer separated and the Aq layer was extracted twice with 300 ml MDC. The organic layer was separated and washed with 300 ml of water followed by 300m1 5% NaCl; and driedthe organic layer with anhydrous sodium sulfate. The organic layer separated and the solvent was distilled out under vacuum. 1 OOm1IPA was added to residue and again distilled under vacuum followed by addition of 800m1 heptane. Filtered the crystallized Material and dried under vacuum at 50C for 12-15 hours to get 96.5% titled compound.BPLC purity:99-99.9% Chiral purity: 99.9%

The synthetic route of 762240-92-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; HARMAN FINOCHEM LIMITED; KADAM, Vijay, Trimbak; SARANAPU, Nareesh; SINGAMPALLI, Sri, Hari; MINHAS, Harpreet, Singh; MINHAS, Gurpreet, Singh; (16 pag.)WO2017/6335; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 63286-28-2, name is 2-Chloro-3-hydrazinylpyrazine, 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 63286-28-2, Safety of 2-Chloro-3-hydrazinylpyrazine

It was stirred for 4 hours at reflux mixture of the compound obtained in Step 1 (8 g) and triethyl orthoformate (32 mL). The reaction solution was cooled to room temperature, the precipitated solid was washed after filtration, with ethanol, To give the title compound followed by drying under reduced pressure (8.10g, 95%).

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; TAIHO PHARMACEUTICAL COMPANY LIMITED; MINAMIGUCHI, KAZUHISA; OKAJIMA, SHIGEO; AOKI, SHINICHI; ASAI, MASANORI; ASAI, TAKAHIRO; YAMANAKA, HIROYOSHI; DOHI, SUGURU; (149 pag.)JP5851663; (2016); B1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 16298-03-6,Some common heterocyclic compound, 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate, molecular formula is C6H7N3O2, 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.

Reference Example 15 3-Iodopyrazine-2-carboxylic acid methyl ester (Reference compound No.15-1) Isoamyl nitrite (5.2 mL, 39 mmol) was added to a suspension of 3-aminopyrazine-2-carboxylic acid methyl ester (1.9 g, 12 mmol) in diiodomethane (20 mL) at 85°C, then the mixture was stirred at 100°C for 15 hours. The reaction mixture was allowed to stand and purified by silica gel column chromatography to give 1.4 g of the title reference compound as a pale yellow solid. (Yield 44percent) 1H-NMR(500MHz,CDCl3) delta 4.04(s,3H),8.47(d,J = 2.1 Hz,1H),8.56(d,J = 2.1 Hz,1H)

The synthetic route of 16298-03-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SANTEN PHARMACEUTICAL CO., LTD.; EP1602647; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem