Tag: M.W=100-200

Reference of 6705-33-5,Some common heterocyclic compound, 6705-33-5, name is Pyrazin-2-ylmethanol, molecular formula is C5H6N2O, 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.

Dissolve 2-pyrazinylmethanol (2.0 g, 18.1 mmol) in DCM (200 mL) and cool to 0C while stirring under nitrogen. Add thionyl chloride (4.63 mL, 63.6 mmol) drop wiseover 10 mm, and allow to warm to 25 C. Stir at room temperature for 16 h. Concentrate the mixture and then dilute with DCM. Wash the crude solution with saturated NaHCO3, dry over Mg504, filter, and concentrate. Dissolve the crude residue in DCM and purify by silica gel flash chromatography (hexane/EtOAc, 95:5 to 100% EtOAc gradient) to give the title compound as a pale yellow oil. 1H NMR (400 MHz, CDC13) oe 4.67 (s = 2H),8.50-8.55 (m, 2H), 8.73 (s, 1H).

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

Reference:
Patent; ELI LILLY AND COMPANY; CHEDID, Marcio; EISSA, Hisham Omer; ENGLER, Thomas Albert; FURNESS, Kelly Wayne; RANK, Kenneth B.; WOODS, Timothy Andrew; WROBLESKI, Aaron D.; WO2015/69512; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 36070-80-1, 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. 36070-80-1 name is 5-Chloropyrazine-2-carboxylic acid, 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.

A RBF was charged with 3-pentyn-2-ol (2.06 mL, 22.08 mmol) and DMF (10 mL). Potassium t-butoxide, sublimed, 99.99% trace metals basis (1.24 g, 11.04 mmol) was added portionwise (cooling with water). The mixture was stirred at room temperature for 10 min until all t-BuOK went into solution, then 5-chloropyrazine-2-carboxylic acid (0.500 g, 3.15 mmol) was added in portions and the resulting brown suspension was heated at 75 C. for 45 minutes. The mixture was cooled to RT and diluted with water (20 ml) until all solids dissolved, then acidified with 2M HCl (5.5 ml) to pH 2. The resulting solution was extracted with EtOAc and the organic layer was washed with water and brine, filtered through a pad of celite and concentrated in vacuo. The resulting suspension was diluted with 3 mL heptane/EtOAc (20:1) mixture then filtered. The solid was washed with heptane and dried in vacuo to afford 5-(pent-3-yn-2-yloxy)pyrazine-2-carboxylic acid (424 mg, 2.056 mmol, 65.2% yield) as a tan solid. m/z (ESI) 207.1 (M+H)+.

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

Reference:
Patent; LEWIS, Richard T.; ALLEN, Jennifer R.; BROWN, James; GUZMAN-PEREZ, Angel; HUA, Zihao; JUDD, Ted; LIU, Qingyian; OLIVIERI, Philip R.; ROMERO, Karina; SCHENKEL, Laurie; STELLWAGEN, John; WHITE, Ryan; US2015/38497; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 56423-63-3, These common heterocyclic compound, 56423-63-3, name is 2-Bromopyrazine, 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 reaction flask were added compound 16 (200 mg, 0.372 mmol), 2-bromopyrazine (50 mg, 0.27 mmol),Pd(dppf)Cl2 (10 mg, 0.01 mmol) and sodium carbonate (60 mg, 0.558 mmol), 5 mL glycol dimethyl ether and 0.9 mLwater were added, bubbled with nitrogen gas for 10 minutes, and the reaction was heated to 100 C in microwave andreacted for half an hour. After TLC detected the reaction was complete, the reaction was concentrated, purified by silicagel column chromatography to afford 35 mg of a product, yield: 20.3%. LC-MS(APCI): m/z = 464.5 (M+1)+. 1H NMR(400 MHz, CDCl3) delta 8.78 (d, J = 2.0 Hz, 1H), 8.73 (s, 1H), 8.64 (s, 1H), 8.54 (d, J = 2.1 Hz, 1H), 8.11 (d, J = 2.0 Hz,1H), 7.95 (s, 1H), 7.67 (d, J = 8.9 Hz, 2H), 7.23 (d, J = 8.6 Hz, 2H), 5.28 (s, 1H), 5.14 (s, 1H), 3.70 – 3.57 (m, 1H), 3.52(d, J = 10.8 Hz, 1H), 3.42 (t, J = 11.6 Hz, 1H), 3.30 (t, J = 9.5 Hz, 1H), 2.26 – 2.17 (m, 1H), 2.02 (dd, J = 9.5, 3.8 Hz, 1H).

Statistics shows that 2-Bromopyrazine is playing an increasingly important role. we look forward to future research findings about 56423-63-3.

Reference:
Patent; Shenzhen Targetrx, Inc.; WANG, Yihan; ZHAO, Jiuyang; AL, Yixin; (55 pag.)EP3553056; (2019); 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 297172-19-1 as follows. Formula: C6H9N3

A flask was charged with tert-butyl (R)-3-((2-(N,N-bis(4- methoxybenzyl)sulfamoyl)-4-iodo-3-(1-(4-methoxybenzyl)-1H-tetrazol-5- yl)phenyl)sulfonamido)pyrrolidine-1-carboxylate and tert-butyl (R)-3-((2-(N,N-bis(4- methoxybenzyl)sulfamoyl)-4-iodo-3-(2-(4-methoxybenzyl)-2H-tetrazol-5- yl)phenyl)sulfonamido)pyrrolidine-1-carboxylate (REFERENCE EXAMPLE 5) (0.15 g, 0.156 mmol), 5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine (0.038 g, 0.313 mmol), Cs2CO3 (0.153 g, 0.469 mmol) and Pd(dppf)Cl2 (0.023 g, 0.031 mmol). The vial was sealed, degassed with N2, and filled with DME (1.56 mL). The resulting mixture was heated overnight at 80 C. The reaction mixture was filtered through diatomaceous earth. The filtrate was concentrated and the residue purified by silica gel column chromatography using (gradient 0-10%) MeOH in DCM as the mobile phase to afford the title compound. LC/MS [M+H]+: 955.82.

According to the analysis of related databases, 297172-19-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; PASTERNAK, Alexander; DONG, Shuzhi; SCOTT, Jack, D.; TANG, Haiqun; ZHAO, Zhiqiang; YANG, Dexi; XIAO, Li; GU, Xin; JIANG, Jinlong; (85 pag.)WO2019/135920; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 4774-14-5, 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. 4774-14-5, name is 2,6-Dichloropyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (LXII) (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 (LXIII) (1.428 g, 9.58 mmol) and the reaction was stirred at 95C for 3 h. The reaction was quenched with water (20 mL) and extracted with EtOAc. The organic layer was dried over anhydrous Na2504, 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 (LXIV) (2.2882 g, 8.04 mmol, 84 % yield) as a white solid. ESIMS found for C12H17C1N402 mlz 285.1 (M+H).

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

Reference:
Patent; SAMUMED, LLC.; KC, Sunil Kumar; WALLACE, David Mark; CAO, Jianguo; CHIRUTA, Chandramouli; MARAKOVITS, Joseph Timothy; BOLLU, Venkataiah; HOOD, John; (307 pag.)WO2017/23989; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 50866-30-3, 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. 50866-30-3 name is 5-Methylpyrazine-2-carbaldehyde, 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.

[011761 (1R,2R)-1-hydroxy-N,N-bis(4-methoxybenzyl)-1-(5-methylpyrazin- 2-yl)propane-2-sulfonamide and (1S,2R)- 1-hydroxy-N,N-bis(4-methoxybenzyl)-1-(5- methylpyrazin-2-yl)propane-2-sulfonamide and (1 S,2S)-1-hydroxy-N,N-bis(4- methoxybenzyl)- 1-(5-methylpyrazin-2-yl)propane-2-sulfonamide and (1R,2S)-1- hydroxy-N,N-bis(4-methoxybenzyl)-1-(5-methylpyrazin-2-yl)propane-2-sulfonamide and Example 564.1. At -78 C, an- butyllithium solution (2.5 M in hexanes, 10.2525.6 mmol) was added to a 2-methyltetrahydrofuran (107 mL) solution containing N,Nbis(4-methoxybenzyl)ethanesulfonamide (7.46 g, 21.36 mmol). The resulting mixture was stirred for 15 mm at -78 C. Next, a 2-methyltetrahydrofuran solution containingmethyl-2-pyrazinecarbaldehyde (2.66 mL, 25.6 mmol) was added at -78 C and thenreaction was allowed to slowly warm to RT and stirred overnight. The reaction was quenched with a saturated ammonium chloride solution and partitioned. The remaining residue was purified on silica eluting with a DCM/EtOAc gradient (0-50%). Desired fractions were then combined and concentrated in vacuo. MS ESI (pos.) mlz: 472.2 (M+H).

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

Reference:
Patent; AMGEN INC.; CHEN, Ning; CHEN, Xiaoqi; CHEN, Yinhong; CHENG, Alan C.; CONNORS, Richard V.; DEIGNAN, Jeffrey; DRANSFIELD, Paul John; DU, Xiaohui; FU, Zice; HEATH, Julie Anne; HORNE, Daniel B.; HOUZE, Jonathan; KALLER, Matthew R.; KHAKOO, Aarif Yusuf; KOPECKY, David John; LAI, Su-Jen; MA, Zhihua; MCGEE, Lawrence R.; MEDINA, Julio C.; MIHALIC, Jeffrey T.; NISHIMURA, Nobuko; OLSON, Steven H.; PATTAROPONG, Vatee; SWAMINATH, Gayathri; WANG, Xiaodong; YANG, Kevin; YEH, Wen-Chen; DEBENEDETTO, Mikkel V.; FARRELL, Robert P.; HEDLEY, Simon J.; JUDD, Ted C.; KAYSER, Frank; (1266 pag.)WO2016/187308; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 55557-52-3, 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 55557-52-3 as follows.

(a). (3-Chloropyrazin-2-yl)methanamine hydrochloride was prepared as follows. To a solution of 3-chloropyrazine-2-carbonitrile (160 g, 1 .147 mol) in acetic acid (1.5 L) was added Raney Nickel (50% slurry in water, 70 g, 409 mmol). The resulting mixture was stirred under 4 bar hydrogen at room temperature overnight. Raney Nickel was removed by filtration over decalite and the filtrate was concentrated under reduced pressure and co-evaporated with toluene. The remaining brown solid was dissolved in ethyl acetate at 50C and cooled on an ice-bath. 2M hydrogen chloride solution in diethyl ether (1 .14 L) was added in 30 min. The mixture was allowed to stir at room temperature over weekend. The crystals were collected by filtration, washed with diethyl ether and dried under reduced pressure at 40C. The product brown solid obtained was dissolved in methanol at 60C. The mixture was filtered and partially concentrated, cooled to room temperature and diethyl ether (1000 ml) was added. The mixture was allowed to stir at room temperature overnight. The solids formed were collected by filtration, washed with diethyl ether and dried under reduced pressure at 40C to give 153.5 g of (3-chloropyrazin-2- yl)methanamine.hydrochloride as a brown solid (74.4 %, content 77 %).

According to the analysis of related databases, 55557-52-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ACERTA PHARMA B.V.; HAMDY, Ahmed; ROTHBAUM, Wayne; IZUMI, Raquel; LANNUTTI, Brian; COVEY, Todd; ULRICH, Roger; JOHNSON, Dave; BARF, Tjeerd; KAPTEIN, Allard; (268 pag.)WO2016/24227; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 33332-29-5, name is 2-Amino-5-chloropyrazine, 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 33332-29-5, Safety of 2-Amino-5-chloropyrazine

Preparation of intermediate BA A mixture of 2-Amino-5-chloropyrazine (CAS [33332-29-5], 6 g, 46.31 mmol) and intermediate J (14.52 g, 69.47 mmol) in EtOH (10 mL) was stirred at 100 C for 12 h. The solvent was removed in vacuum. The residue was purified by column chromatography (petroleum ether/ethyl acetate=5/l). The product fractions were collected and the solvent was evaporated to give intermediate BA, 0.81 g, 7%.

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-Amino-5-chloropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JANSSEN SCIENCES IRELAND UC; GUILLEMONT, Jerome, Emile, Georges; MOTTE, Magali, Madeleine, Simone; RABOISSON, Pierre, Jean-Marie, Bernard; TAHRI, Abdellah; (194 pag.)WO2017/1660; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 19745-07-4,Some common heterocyclic compound, 19745-07-4, name is 2,5-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.

Example 164(S)- -(5-chloropyrazin-2-yl)-3-(2.5-difluoro-4-(methylsulfonyl)phenoxy)-ri.4′-bipiperidinl- -one[00580] A stirred solution of (S)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-[l,4′- bipiperidin]-2-one (Preparation G; 40 mg, 0.103 mmol), DIEA (90 mu, 0.515 mmol), and 2,5-dichloropyrazine (30.7 mg, 0.206 mmol) in DMF (1 mL) was heated atl00° C in a sealed tube for 2 hours. The mixture was cooled, diluted with EtOAc (25 mL), washed with brine, dried over Na2S04 and concentrated in vacuo. The residue was purified by preparative TLC (EtOAc/ DCM 4: 1) to afford (S)-l’-(5-chloropyrazin-2-yl)-3-(2,5-difluoro-4- (methylsulfonyl)phenoxy)-[l,4′-bipiperidin]-2-one (2 mg, 0.004 mmol, 4percent yield) as a white solid. Mass spectrum (apci) m/z = 501.1 (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 2,5-Dichloropyrazine, its application will become more common.

Reference:
Patent; ARRAY BIOPHARMA INC.; AICHER, Thomas Daniel; BENCSIK, Josef Roland; BOYD, Steven Armen; CONDROSKI, Kevin Ronald; FELL, Jay Bradford; FISCHER, John P.; HINKLIN, Ronald Jay; PRATT, Scott Alan; SINGH, Ajay; TURNER, Timothy M.; WO2011/146335; (2011); A1;,
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. 16298-03-6, name is Methyl 2-aminopyrazine-3-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: Methyl 2-aminopyrazine-3-carboxylate

Step 1: synthesis of methyl 3-bromopyrazine-2-carboxylate (99)To a solution of methyl 3-amino-2-pyrazinecarboxylate (13.06 mmol, 2 g) in hydrobromic acid (13.06 mmol, 7.4 ml, 1.057 g) at 0°C was added bromine (38.9 mmol, 2 mL, 6.22 g) drop wise and then a solution of sodium nitrite (33.3 mmol, 2.3 g) in water (4 mL). The reaction was stirred for 2h at 0°C and the reaction mixture was extracted with CH2CI2. Organic layer was dried and evaporated to give crude methyl 3- bromopyrazine-2-carboxylate 101 (1.2gr, 43percent). (m/z) = 217 and 219 (M+H)+.

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

Reference:
Patent; N.V. ORGANON; FOLMER, Brigitte, Johanna, Bernita; MAN, de, Adrianus, Petrus, Antonius; GERNETTE, Elisabeth, Sophia; CORTE REAL GONCALVES AZEVEDO, Rita; IBRAHIM, Hemen; WO2011/147764; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem