Month: April 2021

These common heterocyclic compound, 957344-74-0, name is 5,8-Dibromoimidazo[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. HPLC of Formula: C6H3Br2N3

Step 3 4-(5-Bromo-iotamiotadazo[l 2-a]pyraziotan-8-ylamiotano)-2-methoxy-N-(6-methylpyriotadiotan-3-ylmethyl) benzamide[00367] 5,8-dibromoimidazo[l,2-a]pyrazme (285 mg, 1 03 mmol) and 4-ammo-2-methoxy-/V-[(6-methylpy?dm-3-yl)methyl]benzamide (280 mg, 1 03 mmol) are stirred in 1PrOH (5 mL) and HBr (48% aq , 380 muL) is added The mixture is heated at reflux for 24 hours The cooled suspension is poured into NaHCO3 (sat aq , 25 mL) and water (25 mL) and extracted with CHCI3 (3 x 40 mL) The extracts are dried over MgStheta4 and evaporated The residue is purified by column chromatography, elutmg with 10% – 20% DCM/MeOH to afford the title compound as a pale yellow solid (200 mg, 0 43 mmol)

The synthetic route of 5,8-Dibromoimidazo[1,2-a]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GALAPAGOS N.V.; WO2007/131991; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 89464-87-9, name is 3-Methoxy-5-methylpyrazin-2-amine, 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. Product Details of 89464-87-9

(i) 2-Iodobenzenesulphonyl chloride (obtained as described in J Org Chem, 1977, 42, 3265) (12.1 g) was added to a solution of 2-amino-3-methoxy-5-methylpyrazine (5.6 g) in pyridine (100 ml) and the solution was heated at 70 C. for 8 hours. Volatile material was removed by evaporation and water (200 ml) was added to the residue. The mixture was extracted with ethyl acetate (2*200 ml) and the extracts were washed with 2M hydrochloric acid (200 ml) and water (200 ml). The extracts were dried (MgSO4) and the solvent was removed by evaporation. The residue was triturated with ether to give N-(3-methoxy-5-methyl-2-pyrazinyl)-2-iodobenzenesulphonamide (7.2 g), m.p. 136-138 C.; 1 H NMR (d6 -DMSO): 2.3 (s,3H), 3.9 (s,3H), 7.3 (dt,1H), 7.5-7.65 (m,2H), 8.05-8.15 (m,2H), 10.7-10.8 (br s, 1H).

The synthetic route of 3-Methoxy-5-methylpyrazin-2-amine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zeneca Limited; US5861401; (1999); A;,
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. 54608-52-5, name is 2-Hydrazinopyrazine, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C4H6N4

[00495] Step A: 2-(5 -methyl-4-nitroso-3-phenyl- 1 H-pyrazol- 1 -vDpyrazine. To a solution of 2-hydrazinylpyrazine (0.485 g, 4.40 mmol) in HOAc (6 mL) was added (2- (hydroxyimino)-l-phenylbutane-l,3-dione (0.765 g, 4.00 mmol) in small portions over 2 minutes. The mixture was stirred for 5 minutes and the resulting light orange suspension was stirred at 60 C for 6 hours. EtOH (1 mL) was added and the mixture was heated at 60 C for an additional 6 hours. The resulting dark green suspension was cooled to ambient temperature and the mixture was diluted with H20 (30 mL). The green suspension was stirred for 1 hour and the solid was collected via vacuum filtration. The collected solid was washed with H20 and dried in vacuum. The solid was suspended in EtOH (25 mL) and concentrated HC1 (500 mu) was added. The mixture was heated at reflux for 20 hours, cooled to ambient temperature and diluted with chilled H20 (75 mL). The mixture was treated with 1M NaOH to pH=7 and was extracted with Et20 (3X). The combined extracts were washed with saturated NaCl and dried over MgS04. The dried solution was filtered through packed Celite and concentrated. The residual green-yellow solid was purified on a Si02 column using step gradient elution (25% CH2CI2, 50% EtOAc/hexanes) to furnish the title compound as a turquoise solid (325 mg, 31%). MS (apci) m/z = 266.1 (M+H).

According to the analysis of related databases, 54608-52-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ARRAY BIOPHARMA INC.; BRANDHUBER, Barbara, J.; JIANG, Yutong; KOLAKOWSKI, Gabrielle, R.; WINSKI, Shannon, L.; WO2014/78322; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 98-97-5, name is Pyrazine-2-carboxylic acid, molecular formula is C5H4N2O2, 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 Pyrazine-2-carboxylic acid

Pyrazine-2-carboxylic acid (5 g, 40.3 mmol) was dissolved inMeOH (150 ml), and a few drops of H2SO4 were added. The resultingreaction mixture was refluxed for 2 h. Methanol was evaporated and the resulting reaction mixture was extracted withEtOAc, washed with saturated NaHCO3 solution, then with brineand dried over anhydrous Na2SO4. The solvent was removed invacuo to give the methyl pyrazine-2-carboxylate (5.5 g, yield98%). 1H NMR (CDCl3, 400 MHz) d 9.32 (d, 1H, J = 1.5 Hz), 8.78(d, 1H, J = 2.4 Hz), 8.73 (dd, 1H, J = 2.4, 1.5 Hz), 4.04 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 98-97-5, its application will become more common.

Reference:
Article; Lee, Young Hun; Lee, Jung Min; Kim, Sang Geon; Lee, Yong Sup; Bioorganic and Medicinal Chemistry; vol. 24; 12; (2016); p. 2843 – 2851;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 870787-06-7, name is 3-(Trifluoromethyl)pyrazine-2-carboxylic acid, molecular formula is C6H3F3N2O2, 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. Application In Synthesis of 3-(Trifluoromethyl)pyrazine-2-carboxylic acid

To 74 mg of 3-(trifluoromethyl)pyrazine-2-carboxylic acid in 3 ml of dichloromethane, 10 mg of N,N-dimethylformamide and 57 mg of oxalyl chloride were added, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the solvent was evaporated under reduced pressure, and the resulting residue was dissolved in 10 ml of dichloromethane. To the solution, 89 mg of 2-amino-1-(3,5-dichloropyridin-2-yl)ethanone-O-(tert-butyl)oxime and 39 mg of triethylamine were added with stirring under cooling with ice, and the mixture was stirred at room temperature for another 1 hour. After completion of the reaction, the reaction mixture was mixed with 10 ml of water and extracted with chloroform (10 ml*1), the resulting organic layer was dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 1:9 to 3:7) as the eluent to obtain 22 mg of geometrical isomer A and 111 mg of geometrical isomer B of the desired product as colorless resinous substances.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 870787-06-7, its application will become more common.

Reference:
Patent; Nissan Chemical Industries, Ltd.; IWASA, Motoyoshi; TSUJI, Keisuke; TOMIZAWA, Mitsutaka; MITA, Takeshi; KUWAHARA, Hidehito; ASAHI, Miho; IMANAKA, Hotaka; EP2873658; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 77112-53-9,Some common heterocyclic compound, 77112-53-9, name is Imidazo[1,2-a]pyrazine-2-carboxylic acid, molecular formula is C7H5N3O2, 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.

Under Ar protection, triethylamine (13.1g, 0.12mol) slowly at 0-5 C was added dropwise a toluene solution of compound 85, and stirred for 30 minutes, slowly added diphenylphosphoryl azide ester (23.61g, 85.79mmol), plus complete slowly warmed to room temperature and stirred for 3 h, then slowly added t-butanol (in 50.0 mL), and the mixture was heated to 80 C, stirred overnight, cooled to room temperature, the reaction mixture under reduced pressure concentrated to dryness and the residue dissolved in ethyl acetate, the organic phase was washed three times with saturated NaCl solution, dried over anhydrous Na2SO4Dried, filtered, and evaporated to dryness and the residue was separated by column chromatography (ethyl acetate: petroleum ether = 1: 4-1: 2) to give compound 86 as a white solid, a total of 5.54g (23.58mmol), a yield of 55.0%.

The synthetic route of 77112-53-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Chinese Academy of Sciences, Shanghai Institute of Medicine; Nanjing Changao Pharmaceutical Technology co., LTD; YANG, YU SHE; CAO, XU FENG; LI, ZHAN; LI, WEI; (78 pag.)CN103965194; (2016); B;,
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. 23688-89-3, name is 6-Chloropyrazine-2-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 23688-89-3

6-Chloropyrazine-2-carboxylic acid [CAS RN: 23688-89-3] (565 mg, 3.56 mmol,1.0 eq) was dissolved in 8 mL THF, and CDI (578 mg, 3.56 mmol, 1.0 eq) was added. Then, the reaction mixture was heated to 70C for 2 h. In a separate flask, 1 -(2,2,2-trifluoroethyl)piperidin-4-amine dihydrochloride [Intermediate13] (936 mg, 3.67 mmol, 1.03 eq) was dissolved in THF and triethylamine (1.02 mL, 7.34 mmol, 2.06 eq) was added. Then, this solution was added to thesolution of the preformed imidazolide and the reaction mixture was heated again to 70C for 2 h. 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 558 mg (44% yield of theory) of the title compound.UPLC-MS (Method 1): R = 0.95 mm; MS (EI0): m/z = 323 [M+H].1H-NMR (400 MHz, DMSO-d6): oe [ppm] = 1.63-1.79 (m, 4H), 2.43 (m, 2H), 2.92 (m, 2H), 3.16 (q, 2H), 3.80 (m, 1H), 8.70 (d, 1H), 8.99 (s, 1H), 9.10 (s, 1H).

According to the analysis of related databases, 23688-89-3, the application of this compound in the production field has become more and more popular.

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

Reference 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.

Hydrazine hydrate (24 mL, 0.48 mol) was added dropwise to a stirred mixture of methyl 3-amino-6-bromopyrazine-2-carboxylate 29 (100 g, 0.42 mol) in EtOH (2 L). The mixture was heated at 50 C under nitrogen. The resulting thick suspension was stirred at 50 C for 16 h. Further hydrazine hydrate (2.5 mL) was added in one portion and the suspension was stirred at 50 C for a further 24 h. EtOH (500 mL) was charged to the thick reaction mixture and the mixture was allowed to cool to room temperature. The resulting suspension was filtered and the solid washed with ethanol (1 L) and dried in vacuo to give 3-amino-6-bromopyrazine-2-carbohydrazide (98 g, quantitative) as a cream solid. Pivalic anhydride (165 mL, 815 mmol) was added to a stirred mixture of 3-amino-6-bromopyrazine-2-carbohydrazide (172 g, 741 mmol) in acetonitrile (1.8 L) and the mixture was heated at 80 C for 1 h. The reaction was left to stir for 16 h. The required yellow solid material was isolated by filtration. The filtrate was partitioned between EtOAc (2 L) and aqueous sodium bicarbonate (2 L). The organic layer was washed with saturated brine and dried over MgSO4. The solution was filtered and concentrated to give an orange sticky solid which was triturated with MTBE (250 mL). The insoluble yellow solid was isolated by filtration. The combined solids were dried in vacuum at 50 C for 3 days to afford 3-amino-6-bromo-N’-pivaloylpyrazine-2-carbohydrazide (224 g, 96%) as a yellow solid. p-Toluenesulfonyl chloride (164 g, 862 mmol) was added portionwise to a suspension of 3-amino-6-bromo-N’-pivaloylpyrazine-2-carbohydrazide (227 g, 718 mmol) and DIPEA (300 mL, 1.8 mol) in acetonitrile (2.2 L). The mixture was stirred for 2 h at 70 C. The reaction was left to cool to room temperature overnight. The reaction mixture was partitioned between ethylacetate (2 L) and aq. sodium bicarbonate (2 L). The organic layer was washed with brine, dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting brown/beige solid was triturated with hot MTBE (1 L), isolated by filtration and dried to afford 5-bromo-3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine 30 as a yellow solid (187 g, 87%). The mother liquors were evaporated to dryness. The crude solid was triturated with MTBE (500 mL), filtered and washed with 100 mL of MTBE. The resulting solid was air dried overnight to afford a second crop of 5-bromo-3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine 30 (36 g, 17%).

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:
Article; Barlaam, Bernard; Cosulich, Sabina; Delouvrie, Benedicte; Ellston, Rebecca; Fitzek, Martina; Germain, Herve; Green, Stephen; Hancox, Urs; Harris, Craig S.; Hudson, Kevin; Lambert-Van Der Brempt, Christine; Lebraud, Honorine; Magnien, Francoise; Lamorlette, Maryannick; Le Griffon, Antoine; Morgentin, Remy; Ouvry, Gilles; Page, Ken; Pasquet, Georges; Polanska, Urszula; Ruston, Linette; Saleh, Twana; Vautier, Michel; Ward, Lara; Bioorganic and Medicinal Chemistry Letters; vol. 25; 22; (2015); p. 5155 – 5162;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 33332-28-4, name is 2-Amino-6-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 33332-28-4, Recommanded Product: 2-Amino-6-chloropyrazine

(b) N-(6-Chloro-pyrazin-2-yl)-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide This compound was prepared from 4-hydroxy-2-methyl-N-methyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide, 2-amino-6-chloro-pyrazine and p-toluenesulfonic acid analogous to Example 14. Yield: 68percent of theory. Melting point: 278¡ã-279¡ã C. (decomposition). C14 H11 ClN4 O4 S (366.79): Calc.: C–45.84percent; H–3.03percent; Cl–9.67percent; N–15.28percent; S–8.74percent. Found: C–45.61percent; H–3.14percent; Cl–9.71percent; N–15.02percent; S–8.58percent.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Amino-6-chloropyrazine, and friends who are interested can also refer to it.

Reference:
Patent; Dr. Karl Thomae Gesellschaft mit beschrankter Haftung; US4533664; (1985); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 186534-02-1, 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. 186534-02-1 name is 3,5,6-Trimethylpyrazine-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.

General procedure: New a, b-unsaturated carbonyl-based compounds (5a-g and 6au)were synthesized using direct coupling technique [40] (Scheme 1). The reaction was carried out using base-catalyzed Claisen-Schmidt condensation reaction, by reacting different types of ketoneswith appropriate aromatic aldehyde at molar ratio 2:1 tosynthesize new compounds (5a-g) and at molar ratio 1:1 for (6a-u).For synthesis of 6a-u first 5a-g intermediates were synthesized andin second step appropriate aldehydes were reacted with intermediates.The detailed method of synthesis has already beenreported by us previously [38,40]. Scheme 1 shows the highlights ofsynthesis of compound 3, 4 and a, b-unsaturated carbonyl-basedcompounds along with oxime derivatives. 15 mL ethanol wastaken in a round bottom flask and aromatic aldehyde (20 mmol, 2equivalent) and specific ketone (10 mmol,1 equivalent) were addedand dissolved using a stirrer for 2-3 min at 5 C. Into the abovesolution, 40% NaOH solution in ethanol was added drop wise andthe mixture was stirred for 1-24 h at 27 C. The color change andprecipitate formation in the reaction mixture showed productformation. TLC was used to monitor the reaction and acidified icewas added to quench the reaction once completed. The isolation ofcompounds was done by recrystallization and/or by using columnchromatography.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,5,6-Trimethylpyrazine-2-carbaldehyde, and friends who are interested can also refer to it.

Reference:
Article; Zha, Gao-Feng; Qin, Hua-Li; Youssif, Bahaa G.M.; Amjad, Muhammad Wahab; Raja, Maria Abdul Ghafoor; Abdelazeem, Ahmed H.; Bukhari, Syed Nasir Abbas; European Journal of Medicinal Chemistry; vol. 135; (2017); p. 34 – 48;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem