Month: March 2021

Adding a certain compound to certain chemical reactions, such as: 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, 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 36070-80-1, HPLC of Formula: C5H3ClN2O2

50 ml RBF was charged with 3-pentyn-2-ol (2.063 ml, 22.08 mmol) in DMF (10 ml) and potassium t-butoxide (1.24 g, 11.04 mmol) was added portionwise while stirring (cooling in water bath). The mixture was stirred at room temperature for 10 min until all t-BuOK went into solution, then 5-chloropyrazine-2-carboxylic acid (500 mg, 3.15 mmol) was added in portions and the resulting brown suspension was heated at 75 C. for 45 min. The mixture was cooled to room temperature and diluted with water (20 ml) until all solids dissolved, then acidified with 2M HCl solution (5.5 ml) to pH 2. The resulting solution was extracted with EtOAc, organic layer was washed with water twice then with brine, filtered through 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

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; WHITE, Ryan; ALLEN, Jennifer R.; EPSTEIN, Oleg; HONG, Fang-Tsao; HUA, Zihao; HUMAN, Jason Brooks; LOPEZ, Patricia; OLIVIERI, Philip R.; ROMERO, Karina; SCHENKEL, Laurie; STELLWAGEN, John; TAMAYO, Nuria A.; ZHENG, Xiao Mei; US2014/213581; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 1062608-42-7, name is 5-Bromo-3-iodopyrazin-2-amine, molecular formula is C4H3BrIN3, 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. Quality Control of 5-Bromo-3-iodopyrazin-2-amine

To a solution of 2b (4.0 g, 13.33 mmol) in 1,4-dioxane (55 mL) was added 3- (trifluoromethyl)phenyl boronic acid (6) (2.79 g, 14.67 mmol) followed by 1M aqueous solution of potassium carbonate (26.6 mL, 26.67 mmol) at RT. Reaction mixture was purged with N2 gas for 30 minutes. Bis(triphenylphosphine)palladium(II)chloride (0.65 g, 0.93 mmol) was added to the reaction mixture and was heated to reflux for 4 h, cooled to RT, filtered through celite. Filtrate was concentrated under vacuum to remove dioxane. 50 mL of water was added and extracted with dichloromethane. Organic layer combined and washed with water, dried over sodium sulfate and concentrated under vacuum. Crude product purified by flash chromatography using 30% ethyl acetate in petroleum ether to afford compound 3b (3.5 g, 83.3%) as pale yellow solid. 1H NMR (400 MHz, DMSO-d6): delta 8.14 (s, 1H), 7.90 (d, J = 8.40 Hz, 2H), 7.84 (d, J = 8.40 Hz, 2H), 6.63 (s, 2H). LC-MS APCI: Calculated for C11H7BrF3N3: 318.10; Observed m/z [M+H]+: 318.0.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1062608-42-7, its application will become more common.

Reference:
Patent; MMV MEDICINES FOR MALARIA VENTURE; UNIVERSITY OF CAPE TOWN; WATERSON, David; WITTY, Michael John; CHIBALE, Kelly; STREET, Leslie; GONZALEZ CABRERA, Diego; PAQUET, Tanya; (36 pag.)WO2017/9773; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route 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.

Step 1: Synthesis of Intermediate B’ as described in the general scheme: 2-amino-3-amidopyrazine A mixture of A’ (270 g, 1.763 M), methanol (1.05 L) and liq. Ammonia (25%) (1.68 L) is stirred at 30 C. for 24 hrs. The resulting solid is separated by filtration, washed with water (210 mL*2) and dried at 50-55 C. under vacuum to afford B’, used in the next step without further treatment.

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

Reference:
Patent; WIGERINCK, Piet Tom Bert Paul; ANDREWS, Martin James Inglis; De WEER, Marc Maurice Germain; SABOURAULT, Nicholas Luc; KLUGE, Stefan Christian; US2011/118269; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 912773-21-8, These common heterocyclic compound, 912773-21-8, name is 2-Bromo-5-chloropyrazine, 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.

N2 was bubbled through a solution of the product from step 1 (0.37 mmol) in toluene for 30 min. Separately, a flask was charged with 2-bromo-5-chloropyrazine (108 mg, 0.56 mmol), (Ph3P)4Pd (21.5 mg, 0.19 mmol) and copper(I) iodide (7.1 mg, 0.037 mmol), then sealed evacuated and purged with N2 thrice. The toluene solution was inhjected in to the flask and the solution stirred at 100 C for 3 h 15 min. The cooled solution was concentrated in vacuo to ~1/2 volume. FCC (5-40% EtOAc in cyclohexane) gave the title compound as a solid (97 mg). LCMS (Method A) 4.66 min, ES+ 476 [M+1]+.

Statistics shows that 2-Bromo-5-chloropyrazine is playing an increasingly important role. we look forward to future research findings about 912773-21-8.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; BRONNER, Sarah M.; CRAWFORD, James J.; CRIDLAND, Andrew; CYR, Patrick; FAUBER, Benjamin; GANCIA, Emanuela; GOBBI, Alberto; HURLEY, Christopher; KILLEN, Jonathan; LEE, Wendy; RENE, Olivier; VAN NIEL, Monique Bodil; WARD, Stuart; WINSHIP, Paul; ZBIEG, Jason; (439 pag.)WO2018/83105; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 56423-63-3, The chemical industry reduces the impact on the environment during synthesis 56423-63-3, name is 2-Bromopyrazine, I believe this compound will play a more active role in future production and life.

A sealed microwave vial containing (9R, 135)- 13 -[4-(2-amino-5 -chlorophenyl)-6-oxo- 1 ,6-dihydropyrimidin- 1 -yl]-3 ,9-dimethyl-3 ,4,7, 15 -tetraazatricyclo [12.3.1.026]octadeca- 1(1 8),2(6),4, 14,1 6-pentaen-8-one hydrochloride (0.01 g, 0.017 mmol), prepareddescribed in Example 313, 2-bromopyrazine (5.51 mg, 0.035 mmol) and EtOH (1 ml)was heated in a microwave at 150 C for 30 mm, cooled to rt, and concentrated. To the residue were added Cs2CO3 (0.030 g, 0.093 mmol), Pd(OAc)2 (1.05 mg, 4.66 jimol),Xantphos (5.39 mg, 9.31 jimol), and 2-bromopyrazine (5.51 mg, 0.035 mmol), followeddioxane (0.93 1 ml). The reaction mixture was degassed with Ar for 10 mm. The vial was sealed and heated at 85 C. After 4 h, the reaction was cooled to rt and concentrated. Purification by reverse phase chromatography afforded (9R, 135)-i 3-(4- {5-chloro-2-[(pyrazin-2-yl)amino]phenyl} -6-oxo- 1 ,6-dihydropyrimidin- 1 -yl)-3 ,9-dimethyl-3 ,4,7, 15-tetraazatricyclo[ 12.3.1 .02?6]octadeca- 1(1 8),2(6),4, 14,1 6-pentaen-8-one trifluoroacetate(2.95 mg, 20% yield) as a yellow solid. MS(ESI) m/z: 582.5 (M+H). ?H NMR(400MHz, CD3OD) oe 9.09 (s, 1H), 8.73 (d, J=5.i Hz, 1H), 8.23 – 8.19 (m, 2H), 8.08 (dd,J=2.8, 1.4 Hz, 1H), 7.89 (d, J=2.6 Hz, 1H), 7.73 (s, 1H), 7.67 (d, J2.6 Hz, 1H), 7.53 (dd,J=5.i, 1.5 Hz, 1H), 7.50 (s, 1H), 7.43 (dd, J8.9, 2.5 Hz, 1H), 6.77 (s, 1H), 6.02 (dd,J=12.7, 4.3 Hz, 1H), 4.05 (s, 3H), 2.76 – 2.67 (m, 1H), 2.43 – 2.32 (m, 1H), 2.15 – 2.01 (m, 2H), 1.68 – 1.44 (m, 2H), 1.02 (d, J=6.8 Hz, 3H), 0.81 – 0.65 (m, 1H). Analytical HPLC (Method A): RT = 7.06 mm, 94.0% purity; Factor XIa Ki = 560 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, 2-Bromopyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; CORTE, James R.; DE LUCCA, Indawati; FANG, Tianan; YANG, Wu; WANG, Yufeng; DILGER, Andrew K.; PABBISETTY, Kumar Balashanmuga; EWING, William R.; ZHU, Yeheng; WEXLER, Ruth R.; PINTO, Donald J. P.; ORWAT, Michael J.; SMITH, Leon M. II; WO2015/116886; (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. 24241-18-7, name is 2-Amino-3,5-dibromopyrazine, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C4H3Br2N3

Step 1: synthesis of 3-amino-6-bromopyrazine-2-carbonitrile (14)A solution of copper(i) cyanide (1.20 g, 13.42 mmol) and sodium cyanide (0.658 g, 13.42 mmol) in DMF (10 mL) was heated to 125C. 2-amino-3,5-dibromo pyrazine (2.61 g, 10.32 mmol) was added in portions. The reaction was stirred at 125C, and after 5h quenched in ice cold NaHC03 solution. The black precipitate was filtrated off and the filtrate was extracted (3x) with EtOAc. The organic layer was washed with brine, dried and evaporated. Purification by chromatography (CH2CI2) gave pure 3- amino-6-bromopyrazine-2-carbonitrile 14 (1.38 g, 67.2 %). 1H-NMR (400 MHz, CDC13) 5.29 (br s, 2H), 8.30 (s, 1H). (m/z) = 199 and 201 (M+H)+.

According to the analysis of related databases, 24241-18-7, the application of this compound in the production field has become more and more popular.

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

Related Products of 41270-66-0, 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 41270-66-0 as follows.

30 g of 2-chloro-5,6-diphenylpyrazine and 131.22 g of 4-(isopropylamino)-1-butanol were mixed and then heated with stirring at 190C for 10 hours.. The reaction solution was air-cooled, poured into water, extracted with diethyl ether, dried over anhydrous magnesium sulfate and then concentrated.. The residue was purified by silica gel column chromatography to obtain 22.96 g of the desired compound as a colorless crystal having a melting point of 102 to 103C.

According to the analysis of related databases, 41270-66-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Nippon Shinyaku Co., Ltd.; EP1400518; (2004); 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 59303-10-5 as follows. COA of Formula: C5H5ClN2

A mixture of 5-(4-methanesulfonyl-phenyl)-2-piperidin-4-yl-2,3-dihydro-furo[2,3-c]pyridine (50 mg), 2-chloro-5-methylpyrazine (30 mg), and cesium carbonate (91 mg) in dimethylsulfoxide (1 mL) is heated to 150 C. in a microwave oven. After cooling to room temperature the reaction mixture is diluted with water and extracted with ethyl acetate. The combined extracts are washed with brine, dried over MgSO4, and concentrated in vacuo. The residue is chromatographed on silica gel (ethyl acetate/methanol 98:2?97:3). The crude product is triturated with a small amount of methanol and the precipitate is filtered off, washed with diethyl ether, and dried to give the title compound. LC (method 5): tR=1.08 min; Mass spectrum (ESI+): m/z=451 [M+H]+.

According to the analysis of related databases, 59303-10-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; HIMMELSBACH, Frank; LANGKOPF, Elke; NOSSE, Bernd; US2013/18030; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 6966-01-4, These common heterocyclic compound, 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-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.

Preparation of methyl 3,6-dibromopyrazine-2-carboxylate A mixture of 3 – amino – 6 – bromopyrazine – 2 – carboxylic acid methyl ester (4 ? 6 2 g ’20 mmol), aqueous hydrobromic acid (48%, 24 ml) and acetic acid (3.2 ml) was added to the reactor, -5 C. The solution (20 ml) of the solution of acetic acid (5 ml) and sodium nitrite (4.8 g, 70 ml) was slowly added successively -5 C stirring reaction lh. The reaction was terminated, washed with saturated sodium sulfite solution, extracted with ethyl acetate and water, washed with saturated NaCl solution and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound as an off-white solid.

Statistics shows that Methyl 3-amino-6-bromopyrazine-2-carboxylate is playing an increasingly important role. we look forward to future research findings about 6966-01-4.

Reference:
Patent; NANJING SHENGHE PHARMACEUTICAL CO., LTD.; WANG, YONG; ZHAO, LIWEN; LIU, YANG; ZHANG, JINGZHONG; WANG, DEZHONG; GAO, YIPING; CHEN, HONGYAN; ZHANG, CANG; ZHANG, DI; (68 pag.)TWI523856; (2016); B;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine, 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 875781-43-4, COA of Formula: C6H4BrN3

Under the protection of nitrogen content 60% of NaH 12 mmol suspended in DMF 30 ml in, adding dissolved in 10 ml DMF of the B – 110 37.4 mmol, reaction 1 h after, adding dissolved in 20 ml DMF to toluene sulfonyl chloride 12 mmol, 30 C reaction 8 h after, the reaction mixture of ethyl acetate extraction 2 time, the combined ethyl acetate after drying, after recovering ethyl acetate, petroleum ether ethyl acetate column chromatography (5:1), the obtained product is 3.0 g, yield 86%

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-Bromo-5H-pyrrolo[2,3-b]pyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Zhejiang Normal University; Li Xinsheng; Chen Xueke; Luo Hongmin; (13 pag.)CN109369659; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem