Month: June 2021

Electric Literature 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

Synthetic Route of 23688-89-3, These common heterocyclic compound, 23688-89-3, name is 6-Chloropyrazine-2-carboxylic acid, 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.

6-Chloropyrazine-2-carboxylic acid [CAS RN: 23688-89-3] (300 mg, 1.89 mmol,1 .0 eq) was dissolved in 4 mL THF, and CDI (307 mg, 1 .89 mmol, 1 .0 eq) wasadded. Then, the reaction mixture was heated to 70C for 2 h. Then, 1-(2,2-difluoroethyl)piperidin-4-amine [CAS RN: 1119499-74-9] (320 mg, 1.95 mmol,1.1 eq) and triethylamine (0.54 mL, 2.90 mmol, 2.1 eq) as a solution in 5 mLTHF was added. The reaction mixture was heated to 70C for 2 h. On cooling, the reaction mixture was partitioned between dichlorormethanol/isopropanol (4/1) and water. The organic phase was washed with water and the phases were separated by the use of a Whatman filter. The volatile components were removed in vacuo and the crude material was purified via preparative MPLC(Biotage Isolera; 25 g SNAP cartridge: hexane -> hexane/ethyl acetate 2/1) to give 150 mg (26% yield of theory) of the title compound.UPLC-MS (Method 2): R = 0.95 mm; MS (EI0): m/z = 305 [M+H].

The synthetic route of 23688-89-3 has been constantly updated, and we look forward to future research findings.

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

Electric Literature 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

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., COA of Formula: C4H3BrN2

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

Some common heterocyclic compound, 33332-29-5, name is 2-Amino-5-chloropyrazine, molecular formula is C4H4ClN3, 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. HPLC of Formula: C4H4ClN3

General procedure: To a solution of 5-chloropyrazin-2-amine (0.2 g, 1.54 mmol) in MeOH (3 mL) was added Cu powder (0.13 g, 2.07 mmol), followed by a solution of sodium methoxide in MeOH (0.38 mL, 1.75 mmol). The reaction mixture was stirred at 150C in a sealed tube for 24 h. The reaction mixture was then filtered through Celite, and the filtrate was concentrated in vacuo. The crude product obtained was purified by column chromatography (silica: 100-200 mesh, MeOH:DCM 2-3%) to afford the title compound (0.13 g, 67%). LCMS (ES+) 126 (M+H)+, RT 1.06 minutes (method 1).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 33332-29-5, its application will become more common.

Reference:
Patent; UCB PHARMA S.A.; KATHOLIEKE UNIVERSITEIT LEUVEN, K.U.LEUVEN R&D; BROOKINGS, Daniel Christopher; FORD, Daniel James; FRANKLIN, Richard Jeremy; GHAWALKAR, Anant Ramrao; KULISA, Claire Louise; NEUSS, Judi Charlotte; REUBERSON, James Thomas; WO2013/68458; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route 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

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. 243472-70-0, name is 5-Bromo-2,3-diphenylpyrazine, A new synthetic method of this compound is introduced below., Recommanded Product: 5-Bromo-2,3-diphenylpyrazine

To 50 g (0.161 mol) of 5-bromo-2,3-diphenylpyrazine, 116 g (0.884 mol, 5.5 eq/mol) of 4-(isopropylamino)-butan-1-ol and 13.33 g of KI (0.080 mol, 0.5 Eq/mol) were added. The reaction mixture was stirred, warmed and then heated up to 140C for about 18-20 hrs. The reaction was monitored by TLC up to completion (starting material about 1% by TLC). The reaction mixture was cooled down to room temperature. After the reaction was completed, the following work up step was performed: Option 1 : Ethyl acetate was added (500 mL, 10 vol) and the organic phase was washed with water (150 mL, 3 vol). The organic phase was separated and aqueous phase was extracted with ethyl acetate (150 mL, 3 vol). The organic phases were joined and washed with water (200 mL, 2 vol) three times. The solvent was distilled off under vacuum at not more than (“NMT”) 40C until 1 vol (oil appearance). Option 2: The material (reaction mixture obtained in step a) was dissolved in acetone (250 mL, 5vol), the solution obtained was cooled down to 0C to 5C and anti-solvent / water was added (1000 mL, 20 vol) for 40 minutes, then the suspension was stirred for about 30 minutes at about 0C-5C. The solid material was filtered and washed with water (200 mL, 4 vol). Crude wet product was obtained as yellow solid yielding 101.8 % Weight Yield (WY) (87 % Molar Yield (MY)), HPLC purity 90.8% on area at this stage. The crude material, obtained in either of the above described options, was purified through crystallization from acetone: heptane as follows: to a solution of 4-((5,6- diphenyl-pyrazin-2-yl)(isopropyl)amino)butan-1-ol crude in acetone (175 mL, 3.5 vol) at 0C – 5C, hexane (600 mL, 12 vol) dropwise in about 120 min was added, then the precipitated mixture was cooled down to about -10C and stirred for about 60 min. The product was filtered off and washed with hexane (250 mL, 5 vol) and dried under vacuum at 25C. Pure product was obtained as yellowish solid yielding overall 77.2%, (66.5% MY), HPLC purity 98.2% on area.

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; TEVA PHARMACEUTICALS INTERNATIONAL GMBH; TEVA PHARMACEUTICALS USA, INC.; VILLALVA, Nidia; CANTE, Ivon; AYBAR, Martin; RODRIGUEZ, Angel; TORRES, Alejandro, Guillen; KANTOR, Hana; GAVENDA, Ales; HERRERA, Hugo; JEGOROV, Alexander; LOPEZ, Nydia; (40 pag.)WO2017/40872; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route 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.

The mixture of (9H-fluoren-9-yl)methyl hexahydropyrrolo[3,4-b]pyrrole-1(2H)-carboxylate (100 mg, 0.5 mmol) and 5,7-dichloropyrido[4,3-b]pyrazine (600 mg, 1.8 mmol) in dioxane was stirred at 0 C. for 30 minutes and then at room temperature for 4 hours. The mixture was concentrated, and the residue was purified by chromatography to give the title compound. MS (m/z): 498 (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; HUTCHISON MEDIPHARMA LIMITED; Su, Wei-Guo; Deng, Wei; Ji, Jianguo; US2014/121200; (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. 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, A new synthetic method of this compound is introduced below., COA of Formula: C5H7Cl2N3

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

Electric Literature of 24241-18-7, The chemical industry reduces the impact on the environment during synthesis 24241-18-7, name is 2-Amino-3,5-dibromopyrazine, I believe this compound will play a more active role in future production and life.

(a) Add 2-amino-3,5-dibromopyrazine (10 g, 39.54 mmol, 1 eq) to a 100 mL autoclaveAnd ammonia (50 mL, commercially available),Raise the temperature to 130 C under nitrogen protection conditions and carry out the reaction overnight (10 to 12 hours);Cooling, suction filtration,The obtained solid was vacuum dried to give 5.0 g of Compound II.

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-3,5-dibromopyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Suzhou Derivative Biological Technology Co., Ltd.; Liu Ke; (6 pag.)CN108395436; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem