Tag: M.W=100-200

6863-74-7, 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. 6863-74-7, name is 6-Chloropyrazine-2-carbonitrile belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below.

General procedure: To an oven-dried microwave vial was added ethyl 2-amino-1,3-oxazole-5-carboxylate (546 mg, 3.50 mmol), Cs2CO3 (2279 mg, 6.99 mmol), Pd2(dba)3 (80 mg, 0.09 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (152 mg, 0.26 mmol) and the vial was capped and purged with nitrogen. 2,4-Dichloropyridine (0.378 mL, 3.50 mmol) was added via syringe, followed by 1,4-dioxane (18 mL) (degassed) and the reaction mixture was heated to 160 C for 1 h under microwave irradiation. CH2Cl2 (40 mL) was added to the crude reaction mixture together with silica (5 g). The solvents were removed under reduced pressure and the crude product was purified by flash silica chromatography with CH2Cl2 (containing 1% methanolic ammonia) as eluent.The resulting brown solid was triturated with Et2O to give ethyl 2-(4-chloropyridin-2-ylamino)oxazole-5-carboxylate (626 mg, 67%) as a pale yellow solid, which was collected by filtration and dried under vacuum.

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

Reference:
Article; Noonan, Gary M.; Dishington, Allan P.; Pink, Jennifer; Campbell, Andrew D.; Tetrahedron Letters; vol. 53; 24; (2012); p. 3038 – 3043;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

98-97-5, A common compound: 98-97-5, name is Pyrazine-2-carboxylic acid, belongs to Pyrazines compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

General procedure: Under Argon, a stirred solution of carboxylic acid (0.37 mmol,1.0 eq.) and Et3N (0.48 mmol, 1.3 eq.) in dry THF (7 mL) was cooledto 10 C. Ethyl chloroformate (0.55 mmol, 1.5 eq.) was drop wiseadded and the resulting mixture was stirred for 2 h. Afterwards, asolution of sodium azide (0.63 mmol, 1.7 eq.) in water (2 mL) wasadded in one portion. After 1 h at 10 C, the reactionwas found tobe complete (TLC) and was quenched into iced water (5 mL). Themixture was extracted with EtOAc (3 10 mL) and the combinedorganic layers were successively dried over MgSO4, filtered andevaporated. The crude acyl azide was placed in dry toluene (20 mL)and heated at reflux for 1 h to give the corresponding crude isocyanate.The latter was placed in dry dioxane (7 mL) prior to addingthe appropriate amine 8, 9 or 10 (0.37 mmol, 1.0 eq.). The solutionwas heated at 100 C for 24 h. The reaction mixture was cooled andthe volatiles were removed to dryness in vacuum at 40 C.

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, Pyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Boulahjar, Rajaa; Ouach, Aziz; Bourg, Stephane; Bonnet, Pascal; Lozach, Olivier; Meijer, Laurent; Guguen-Guillouzo, Christiane; Le Guevel, Remy; Lazar, Said; Akssira, Mohamed; Troin, Yves; Guillaumet, Gerald; Routier, Sylvain; European Journal of Medicinal Chemistry; vol. 101; (2015); p. 274 – 287;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

4858-85-9, 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 4858-85-9 as follows.

A 12L 3-neck round bottom flask fitted with a magnetic stirrer under nitrogen was charged with zinc dust (745 g, pre-activated, 11.4 mol, 2 eq.) and DMA (2 L, anhydrous). 1, 2-dibromoethane (71 mL, 0.855 mol, 0.15 eq, Aldrich) was then added over 10 minutes, followed by TMSC1 (108 mL, 0.855 mol, 0.15 eq, Acros) over 20 minutes. The reaction mixture was stirred for 25 minutes at room temperature. A solution of N-Boc-3-iodoazetidine (2420 g, 8.55 mol, 1.5 eq, CNH Technologies) in DMA (5 L, anhydrous) was added via a 2L addition funnel over 2 h keeping the internal temperature below 65 C using a water bath. The suspension was stirred for 1 hour at RT at which point it was degassed with nitrogen. Stirring was stopped and the suspension was allowed to stand. A 22L 3-neck round bottom flask fitted with a mechanical stirrer was charged with 2, 3-dichloropyrazine (850 g, 5.70 mol, 1.0 eq, AK Scientific), PdCl2dppf-CH2Cl2 (140 g, 171 mmol, 0.03 eq, Aldrich), Cul (67.3 g, 353 mmol, 0.062 eq, Aldrich), and DMA (5 L, anhydrous). The solution was degassed with nitrogen. The clear zinc reagent solution above the residual solid zinc was poured into the 22L flask under nitrogen. The brown solution was degassed with nitrogen and heated to 80 C for 16 hours at which point LCMS indicated complete conversion of 2, 3-dichloropyrazine. The reaction mixture was transferred to brine (8 L) in 50L separatory funnel. Water (8 L) and EtOAc (15 L) were added and the layers were separated. The aqueous layer was extracted with EtOAc (2 x 10 L). The combined organics were washed with water (3 x 10 L) and brine (5 L), dried over sodium sulfate and evaporated. The resulting residue was purified by column chromatography (eluting with hexanes/ethyl acetate = 10: 1) to get 536 g of pure tert-butyl 3-(3-chloropyrazin-2- yl)azetidine- 1 -carboxylate and 121 g of mixed fractions. The impure material was distilled under high vacuum to remove the impurity (N-Boc-azetidine) to give 81 g of pure tert-butyl 3- (3-chloropyrazin-2-yl)azetidine- 1 -carboxylate.Total: 617g, Yield: 40%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4858-85-9, and friends who are interested can also refer to it.

Reference:
Patent; AMGEN INC.; ALLEN, Jennifer; FROHN, Michael; HARRINGTON, Paul; PICKRELL, Alexander; RZASA, Robert; SHAM, Kelvin; HU, Essa; WO2011/143366; (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. 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 36070-80-1

Preparation of Starting Material 5-chloro-N,N-dimethylpyrazine-2-carboxamide (SM-1) 5-chloropyrazine-2-carboxylic acid (1.00 gram, 6.31 mmol) in dichloromethane (30 ml) was treated with catalytic amount of dimethylformamide, followed by (COCl)2 (0.85 ml, 9.46 mmol). The resulting mixture was stirred over night. The reaction was concentrated in vacuo, and dried under vacuum to give desired 5-chloropyrazine-2-carbonyl chloride as solid (1.05 g, 100%).

The synthetic route of 36070-80-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Pfizer Inc; US2010/234285; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 55557-52-3, name is 3-Chloropyrazine-2-carbonitrile, molecular formula is C5H2ClN3, 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. 55557-52-3

Step 1. Preparation of N-(3-cyano-pyrazin-2-yl)-N-methyl-methane sulfonamide (B2-1): A solution of chloropyrazine-2-carbonitrile (4.2 g, 30.21 mmol) in acetonitrile (200 mL) at 25 C. was treated sequentially with Cs2CO3 (13.7831 g, 42.293 mmol) and N-methyl-methane sulfonamide (3.957 g, 36.25 mmol). The mixture was then heated to 80 C. After about 20 hours the mixture was cooled to 25 and filtered. The solids were washed with EtOAc (3*25 mL) and the combined filtrates were concentrated. The resultant residue was treated with water (50 mL) and extracted with EtOAc (3*75 mL). The combined organic layers were washed with water (50 mL), brine, dried over anhydrous sodium sulfate and concentrated. The resultant residue was purified by column chromatography (100-200 mesh silica gel; 40% EtOAc in petroleum ether as eluding solvent) to provide B2-1 as a pale brown liquid. Yield: 4.7 g, 73.43%). 1H NMR (CDCl3) delta: 8.92 (d, 2H), 3.4 (s, 3H) and 3.25 (s, 3H). Mass: (M+1) 213 calculated for C7H8N4O2S. (Note: The product contained unreacted N-methanesulfonamide as an impurity.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 55557-52-3, its application will become more common.

Reference:
Patent; Pfizer Inc.; US2009/54395; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 38557-72-1 name is 2-Chloro-3,5-dimethylpyrazine, 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. 38557-72-1

Part 1, Step B: A mixture of 2-chloro-3,5-dimethylpyrazine (28.5 g, 0.2 mol), prepared above, CuO (0.8 g, 0.01 mol) and concentrated aqueous NH3 (28-30 %, 150 mL) was stirred in a sealed pressure vessel at 150 C for 3 days. After cooling, the mixture was concentrated to dryness and the residue was treated with ethyl acetate (500 mL), then stirred for 15 minutes and filtered. The precipitate was washed with additional ethyl acetate (about 1.5 L) until the starting material was no longer detected in the filtrate. The filtrates were combined and concentrated. The residue was chromatographed on a silica gel column (MeOH/CH2Cl2, 0-10%) to furnish a yellow/brownish solid (20.7 g, 84%). 1H NMR (500 MHz, CHLOROFORM-^) delta ppm 7.68 (1H, s), 2.46 (3H, s), 2.42 (3H, d, J=0.63 Hz).

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

Reference:
Patent; PTC THERAPEUTICS, INC.; CHEN, Guangming; DAKKA, Amal; KARP, Gary Mitchell; LI, Chunshi; NARASIMHAN, Jana; NARYSHKIN, Nikolai; WEETALL, Maria L.; WELCH, Ellen; ZHAO, Xin; WO2013/112788; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A common compound: 23688-89-3, name is 6-Chloropyrazine-2-carboxylic acid, belongs to Pyrazines compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 23688-89-3

General procedure: The compounds were prepared following a literature procedure.57 To a solution of carboxylic acid (1.0 equiv.) in anhydrous CH2Cl2(0.1 M) was added oxalyl chloride (1.5 equiv.) and DMF (0.1 equiv.) at0 C, and the resulting mixture was allowed to warm to RT for 2 h. Thenthe volatiles were concentrated under reduced pressure, and the residuewas dissolved in anhydrous CH2Cl2 (0.1 M), followed by the addition ofaniline (1.0 equiv.) and triethylamine (1.1 equiv.), and the resultingmixture was stirred at RT for another 2 h. After completion monitoredby TLC, the reaction mixture was quenched with H2O and extractedwith CH2Cl2 (3¡Á20 mL), and washed with 1% HCl solution, and thensat. Na2CO3 (aq.). The combined organic layers were dried over MgSO4and concentrated in vacuo.

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, 23688-89-3, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Zhou, Qingqing; Reekie, Tristan A.; Abbassi, Ramzi H.; Indurthi Venkata, Dinesh; Font, Josep S.; Ryan, Renae M.; Munoz, Lenka; Kassiou, Michael; Bioorganic and Medicinal Chemistry; vol. 26; 22; (2018); p. 5852 – 5869;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

123-32-0, These common heterocyclic compound, 123-32-0, name is 2,5-Dimethylpyrazine, 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 3,6-dimethyl-2- (4-methylphenyl) benzoyl pyrazine, comprising the steps of: (1) Take 0.2 mmol 2,5-dimethyl pyrazine, methyl benzoyl formate 0.4mmol, 0.02 mmol silver phosphate, potassium persulfate 0.4mmol 5mL reaction tube was placed in dichloromethane was added 1.4mL , 0.6 mL of distilled water was added, and the mixture was placed in an oil bath at 40 heated, reaction 24h, cooled to room temperature to obtain a reaction solution;(2) The step (1) the resulting reaction mixture was directly concentrated to give a concentrate, the concentrate with ethyl acetate / petroleum ether = 1/2 (v / v) as the developing solvent, separation by thin layer chromatography to give 39mg target The product yield was 87%.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 123-32-0.

Reference:
Patent; Henan Agricultural University; Wu Zhiyong; Zhao Mingqin; Li Yuan; (10 pag.)CN108101856; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

38557-72-1, A common compound: 38557-72-1, name is 2-Chloro-3,5-dimethylpyrazine, belongs to Pyrazines compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

1.42 g of 2-chloro-3,5-dimethylpyrazine which was obtained as the intermediate obtained in the Step 1 of the above synthesis example 2, 1.40 g of 4-fluorophenyl boronic acid, 1.06 g of sodium carbonate, 0.046 g of bis(triphenylphosphine)palladium(II)dichloride (abbreviation : Pd(PPh3)2Cl2), 15 mL of water, and 15 mL of acetonitrile were put in an eggplant flask equipped with a reflux pipe, and the inside thereof was substituted by argon. This reaction container was subjected to irradiation with microwave (2.45 GHz, 100W) for 10 minutes to be heated. Then, water was added to this solution, and extraction using dichloromethane was conducted and an organic layer was extracted. The organic layer obtained was washed with water and dried with magnesium sulfate. After the drying, the solution was filtrated. A solvent of this solution was distilled off. Then the residue obtained by the distillation was purified by silica gel column chromatography which uses dichloromethane as a developing solvent; thereby obtaining an objective pyrazine derivative HdmFppr (white powder, yield of 77 %). A synthetic scheme of Step 1 is shown by the following (a-3).

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

Reference:
Patent; SEMICONDUCTOR ENERGY LABORATORY CO., LTD.; WO2008/149828; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

23611-75-8, A common compound: 23611-75-8, name is Methyl 6-chloropyrazine-2-carboxylate, belongs to Pyrazines compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

Example 66Methy[ 6- ({4-[(3,4-dif[uoropheny[)carbamoy[]-3-methy[- 1 ,2-thiazo[-5-y[lamino)-pyrazine-2-carboxy[ate A mixture of 5-amino-N-(3,4-dif[uoropheny[)-3-methy[-1 ,2-thiazo[e-4-carboxamide [Intermediate 3] (150 mg, 0.56 mmo[, 1.0 eq), methy[ 6-ch[oropyrazine-2- carboxy[ate [CAS RN: 23611-75-8] (120 mg, 0.56 mmo[, 1.0 eq) and cesiumcarbonate (417 mg, 1.28 mmo[, 2.3 eq) in 5.4 mL dioxane/DMF (7/1) was p[aced ina microwave via[ and f[ushed with argon. Then, pa[[adium(II) acetate (13 mg,0.06 mmo[, 0.1 eq) and Xantphos (32 mg, 0.06 mmo[, 0.1 eq) were added. The via[was capped and the reaction mixture was stirred at an environmenta[ temperatureof 110 C overnight. On coo[ing, the vo[ati[e components were removed in vacuo.The crude materia[ was disso[ved in a sma[[ amount DM50 and fi[tered. Purificationwas conducted via preparative HPLC (method A) to give 10 mg (4 % yie[d of theory) of the tit[e compound.UPLC-MS (Method 1): R = 1.20 mm; MS (ESIneg) m/z = 404 [M-H].1H-NMR (400 MHz, DMSO-d6): oe [ppm] = 3.98 (s, 3H), 7.38-7.53 (m, 2H), 7.95 (m,1H), 8.73 (s, 1H), 8.84 (s, 1H), 10.48 (s, 1H), 11.22 (s br, 1H), 1xCH3 not assigned.

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, Methyl 6-chloropyrazine-2-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BAeRFACKER, Lars; PRECHTL, Stefan; SIEMEISTER, Gerhard; WENGNER, Antje Margret; ACKERSTAFF, Jens; NOWAK-REPPEL, Katrin; BADER, Benjamin; LIENAU, Philip; STOeCKIGT, Detlef; WO2014/118186; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem