Month: September 2021

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, A new synthetic method of this compound is introduced below., Product Details of 939412-86-9

The solution of 2- (5-chloro-2-isopropoxy-4-methyl-3- (6- (trifluoromethyl) pyridin-3-yl) phenyl) propanoic acid (680 mg, 1.6 mmol) , (3-chloropyrazin-2-yl) methanamine hydrochloride (366 mg, 2.56 mmol) , Benzotriazole-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (1.25 g, 2.4 mmol) and N, N-Diisopropylethylamine (413 mg, 3.2 mmol) in DMF (10 mL) was stirred at room temperature for overnight. After completed, the solvent was evaporated in vacuo and the residue was dissolved with ethyl acetate. The mixture was washed with water, brine and dried over Na 2SO 4, filtered and evaporated in vacuo to give the product (850 mg) which was used directly for the next step without further purification. MS (M+H) + 527.1, 529.1.

The synthetic route of 939412-86-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BEIGENE, LTD.; LI, Jing; ZHAO, Haibo; WANG, Zhiwei; (193 pag.)WO2018/103688; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., 33332-25-1

Preparation of 5-Chloropyrazine-2-carboxylic acid To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added methyl 5-chloropyrazine-2-carboxylate (1.0 eq) and tetrahydrofuran (4.92 vols) under a nitrogen atmosphere. The reaction mixture was agitated until all the solid had dissolved, then filtered into a second flask. Water (8.65 vols) was added to the reaction mixture and the mixture agitated for approximately 15 minutes. Potassium carbonate (2.1 eq) was added to the reaction mixture and the mixture agitated for 16 hours at 20-25 C. Then 32% w/w hydrochloric acid (3.76 eq) was added over 3 hours in small portions, keeping the reaction temperature 20-25 C., to a pH end point of pH2.2. The resultant slurry was heated to approximately 35-40 C. and then distilled under vacuum at this temperature distilling approximately 5.3 vols, to a final volume of approximately 9.3 vols. The mixture was then cooled to 20-25 C. over at least 2 hours, agitated for 10 hours at this temperature and then filtered. The solid was washed with water (2.8 vols), and the wet product produced dried at 35 C. in a vacuum oven. The desired product was obtained as a solid (corrected yield 91%) 1H NMR delta (400 MHz CDCl3): 7.20 (1H, bs), 8.72 (1H, s), 9.21-9.21 (1H, m); m/z 157 (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; AstraZeneca AB; US2010/210621; (2010); 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. 56423-63-3, name is 2-Bromopyrazine, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 56423-63-3

Preparation 133 2-Chloro-4-(pyrazin-2-yl)aniline To a mixture of 4-amino-3-chlorophenylboronic acid pinacol ester (0.110 g, 0.434 mmol), 2-bromopyrazine (0.090 g, 0.56 mmol), 1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) DCM complex (24 mg, 0.029 mmol) was added anhydrous DME (3.0 mL) followed by 2M aqueous sodium carbonate (0.53 mL, 1.06 mmol). The microwave vial was heated at 75 C. for 40 minutes under microwave irradiation. Further catalyst (0.012 g) was added and the vial was heated at 90 C. for 25 minutes under microwave irradiation. Further 2-bromopyrazine (0.060 g), catalyst (12 mg) and 2M aqueous sodium carbonate (0.25 mL) were added and the reaction mixture was heated at 90 C. for an additional 30 minutes under microwave irradiation. The reaction was partitioned between ethyl acetate (60 mL) and a saturated aqueous NaHCO3 solution (15 mL). The organic layer was washed with a saturated aqueous NaHCO3 solution (2*15 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purified using preparative TLC eluting with 7% ethyl acetate in CH2Cl2. The product band was recovered and stirred with 2% MeOH in ethyl acetate/CH2Cl2 (v/v; 1:10) (20 mL). The silica was removed by filtration, washed with ethyl acetate/CH2Cl2 (v/v; 1:5) (2*5 mL) and acetone (3*4 mL) to give the title compound as an off-white solid (0.039 g, 44%). 1H-NMR (500 MHz, DMSO-d6) 5.86 (s, 2H), 6.89 (d, J=8.5, 1H), 7.85 (dd, J=2.1, 8.5 Hz, 1H), 8.02 (d, J=2.1 Hz, 1H), 8.44 (d, J=2.5 Hz, 1H), 8.57 (dd, J=1.6, 2.5 Hz, 1H), 9.12 (d, J=1.5 Hz, 1H).

According to the analysis of related databases, 56423-63-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; Bavetsias, Vassilios; Atrash, Butrus; Naud, Sebastien Gaston Andre; Sheldrake, Peter William; Blagg, Julian; US2013/345181; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 54608-52-5, These common heterocyclic compound, 54608-52-5, name is 2-Hydrazinopyrazine, 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 solution of 2-hydrazinopyrazine (1.10 g) in trifluoroacetic anhydride (10 mL) was stirred at room temperature for 4 h. To the mixture was added PPA (12 mL). The reaction mixture was heated at 80 C for another 15 h. The reaction mixture was cooled to room temperature and filtered to afford the title compound as a white solid (0.94 g, 50.00 %). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 189.0 (M+l); ? NMR (400 MHz, CDC13) ?: 8.64 (s, 3H).

The synthetic route of 54608-52-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; ZHANG, Jiancun; ZHANG, Yingjun; ZHANG, Weihong; LIU, Bing; ZHANG, Jiquan; LIU, Jinlei; ZHANG, Lu; WO2013/71697; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 4949-13-7, The chemical industry reduces the impact on the environment during synthesis 4949-13-7, name is 2-Fluoropyrazine, I believe this compound will play a more active role in future production and life.

General procedure: To a 5 mL vial containing a stir bar, 3-(2-aminopyrimidin-5-yl)-6-cyclobutyl-2-fluorophenol (80 mg, 0.31 mmol) and 2-chloropyrimidine (41 mg, 0.34 mmol) were added Cs2CO3 (203 mg, 0.62 mmol) and DMSO (0.8 mL). The resultant mixture was stirred at 120 Celsius for approximately 1 hour via microwave irradiation. The reaction mixture was cooled to room temperature before passing the mixture through a syringe filter and subjecting the filtrate to FCC to afford the title compound (81 mg, 78%). The title compound was prepared using conditions similar to those described in Example 160 with DMSO as the solvent, heating for 2 hours at 80 Celsius via microwave radiation and substituting Intermediate B and 2-fluoropyrazine. MS (ESI): mass calcd. for C18H16FN6O, 337.13; m/z found, 337.9 [M+H]+. 1H NMR (400 MHz, CDCl3) delta 8.53 (d, J=1.3 Hz, 1H), 8.49-8.42 (m, 1H), 8.27 (d, J=2.7 Hz, 1H), 8.12-8.03 (m, 2H), 7.85-7.76 (m, 1H), 7.23 (s, 1H), 4.70 (s, 2H), 3.68-3.56 (m, 1H), 2.26-2.08 (m, 4H), 2.03-1.89 (m, 1H), 1.87-1.76 (m, 1H).

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-Fluoropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; Eccles, Wendy; Fitzgerald, Anne E.; Hack, Michael D.; Hawryluk, Natalie A.; Jones, William M.; Keith, John M.; Krawczuk, Paul; Lebsack, Alec D.; Liu, Jing; Mani, Neelakandha S.; McClure, Kelly J.; Meduna, Steven P.; Rosen, Mark D.; US2014/221310; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 14508-49-7, name is 2-Chloropyrazine, A new synthetic method of this compound is introduced below., Formula: C4H3ClN2

2-Chloropyrazine (7.79 mL, 87 mmol, commercially available e.g. from Sigma- Aldrich or Haiso PharmChem) was dissolved in ethanol (50 mL), and hydrazine hydrate (6.85 mL, 218 mmol) was added. The solution was refluxed for 6 hours. The mixture was cooled to room temperature and the solvent was partially evaporated. The residue was diluted with water and extracted with 10% (v/v) of 2-propanol/Dichloromethane solution (5 extractions). The combined organic phases were then dried and evaporated to give a yellow solid which was triturated with diethyl ether to give 2-hydrazinopyrazine as a yellow solid (3.32 g).

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; DEAN, David Kenneth; MUNOZ-MURIEDAS, Jorge; SIME, Mairi; STEADMAN, Jon Graham Anthony; THEWLIS, Rachel Elizabeth Anne; TRANI, Giancarlo; WALTER, Daryl Simon; WO2010/125102; (2010); 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. 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, This compound has unique chemical properties. The synthetic route is as follows., name: (3-Chloropyrazin-2-yl)methanamine hydrochloride

(c) (6R,8aS)-N-((3-chloropyrazin-2-yl)methyl)-3-oxo-1-vinylhexahydro-1H-oxazolo[3,4-a]pyridine-6-carboxamide To a solution of (6R,8aS)-3-oxo-1-vinylhexahydro-1H-oxazolo[3,4-a]pyridine-6-carboxylic acid (60 mg, 0.28 mmol) in DCM (5 mL) was added (COCl)2 (54.1 mg, 0.43 mmol) at 0 C. and stirred at 20 C. for 1 h under N2 atmosphere. The mixture was concentrated in vacuo to give the residue, which was dissolved in THF (2 mL) and followed by (3-chloropyrazin-2-yl)methanamine hydrochloride (76.7 mg, 0.43 mmol) and Et3N (86.2 mg, 0.85 mmol). The mixture was stirred at 20 C. for 5 h. TLC (PE: THF=1:1) showed the starting materials was consumed completely. Then the reaction mixture was poured into water (10 mL), extracted with EA (10 mL*2). The organic layer was concentrated in vacuo and purified with pre-TLC to afford (6R,8aS)-N-((3-chloropyrazin-2-yl)methyl)-3-oxo-1-vinylhexahydro-1H-oxazolo[3,4-a]pyridine-6-carboxamide (30 mg, yield 31.4%) as a white solid. 1HNMR (400 MHz, Methanol-d4): delta=8.53 (dd, J=1.0, 2.5 Hz, 1H), 8.34 (d, J=2.0 Hz, 1H), 6.04-5.88 (m, 1H), 5.50-5.31 (m, 2H), 4.65-4.57 (m, 3H), 3.98-3.89 (m, 1H), 3.83 (ddd, J=3.4, 8.2, 11.8 Hz, 1H), 3.50-3.42 (m, 1H), 2.58-2.42 (m, 1H), 2.10 (dd, J=2.5, 12.8 Hz, 1H), 2.03-1.95 (m, 1H), 1.77-1.63 (m, 2H), 1.53-1.38 (m, 111).

According to the analysis of related databases, 939412-86-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; KIM, RONALD M.; Liu, Jian; Gao, Xiaolei; Boga, Sobhana Babu; Guiadeen, Deodialsingh; Kozlowski, Joseph A.; Yu, Wensheng; Anand, Rajan; Yu, Younong; Selyutin, Oleg B.; Gao, Ying-Duo; Wu, Hao; Liu, Shilan; Yang, Chundao; Wang, Hongjian; US2014/206681; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 6966-01-4,Some common heterocyclic compound, 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, molecular formula is C6H6BrN3O2, 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.

(Step 8-iv) Methyl 3-amino-6-bromopyrazine-2-carboxylate (700 mg, 3 mmol) was dissolved in dioxane (4 mL) with 3-furan boronic acid (0.36 g, 3.2 mmol), potassium acetate (980 mg 10 mmol) and tetrakispalladium triphenylphosphine (200 mg, 0.17 mmol) in a microwave vessel. Nitrogen was bubbled through for 5 minutes, followed by sealing the vessel and microirradiating the mixture for 20 minutes at 170 0C. The reaction mixture was diluted with ethyl acetate/saturated sodium bicarbonate, dried over sodium sulfate, and concentrated to give a solid, which was purified by silica gel column chromatography (0 to 70 % EtOAc/hexanes) to give methyl 3-amino-6-(furan-3- yl)pyrazine-2-carboxylate as a solid. This methyl ester was dissolved in THF/MeOH and an aqueous solution of LiOH hydrate (150 mg, 3.6 mmol) was added. The reaction mixture was stirred for 1 hour at room temperature, concentrated to half the volume, and diluted with ethyl acetate/10% aqueous citric acid solution. The organic layer was washed with brine, dried, and concentrated in vacuo to yield 3-amino-6-(furan-3-yl)pyrazine-2- carboxylic acid as a solid (0.46 g, 2.3 mmol, 77 % overall yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-amino-6-bromopyrazine-2-carboxylate, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2008/36272; (2008); 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 5521-61-9 as follows. SDS of cas: 5521-61-9

INTERMEDIATE 71 PREPARATION OF (6-METHYLPYRAZIN-2-YL)METHANOL To a solution of 6-methylpyrazine-2-carboxylic acid (8.00 g, 58.0 mmol) in N,N- dimethylformamide (50 mL) were added Cs2CO3 (37.8 g, 116 mmol) and iodomethane (12.3 g, 87.0 mmol). After being stirred overnight at room temperature, the reaction mixture was quenched with water (100 mL) and extracted with EtOAc (5 x 150 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was then diluted with water (50 mL). NaBH4 (12.5 g, 330 mmol) was added portionwise at 0 C. After addition, the resulting mixture was stirred at room temperature for 30 min, cooled to 0 C, diluted with water (150 mL) and extracted with EtOAc (8 x 100 mL). The combined organic layers were washed with brine (200 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to afford the title compound (2.9 g, crude) as a yellow solid.1H NMR (400 MHz, DMSO-d6) delta 8.50 (s, 1H), 8.42 (s, 1H), 5.55 (t, J = 5.8 Hz, 1H), 4.59 (d, J = 5.5 Hz, 2H), 2.47 (s, 3H).

According to the analysis of related databases, 5521-61-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; DENALI THERAPEUTICS INC.; BONANOMI, Giorgio; ESTRADA, Anthony A.; FENG, Jianwen A.; FOX, Brian; LESLIE, Colin Philip; LYSSIKATOS, Joseph P.; NAPOLITANO, Carmela; POZZAN, Alfonso; SUDHAKAR, Anantha; SWEENEY, Zachary K.; TONELLI, Federica; DE VICENTE FIDALGO, Javier; (232 pag.)WO2017/96301; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 939412-86-9, These common heterocyclic compound, 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, 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.

2- (5-chloro-2-ethoxy-4-methyl-3- (6-methylpyridin-3-yl) phenyl) propanoic acid (2.7 g, 8.09 mmol) , (3-chloropyrazin-2-yl) methanamine hydrochloride (1.4 g, 9.71 mmol) , HOBt (1.32 g, 24.27 mmol) , EDCI (1.86 g, 9.71 mmol) and DIPEA (3.14 g, 24.27 mmol) were dissolved in THF (30 mL) and stirred at room temperature under N 2 for overnight, brine (20 mL) was added and extracted with ethyl acetate. The combined organic layers were washed with brine and dried over Na 2SO 4. The product (3.2 g in 86.1 %yield) was got. MS (ESI) m/e (M+1) +459.

The synthetic route of 939412-86-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BEIGENE, LTD.; LI, Jing; ZHAO, Haibo; WANG, Zhiwei; (193 pag.)WO2018/103688; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem