330786-09-9 Archives

September 18, 2021 News Sources of common compounds: 330786-09-9

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3,5-dichloropyrazine-2-carboxylate, its application will become more common.

Synthetic Route of 330786-09-9,Some common heterocyclic compound, 330786-09-9, name is Methyl 3,5-dichloropyrazine-2-carboxylate, molecular formula is C6H4Cl2N2O2, 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 Methyl 3,5-dichloropyrazine-2-carboxylate Jl (lOg, 48.3 mmol) was treated with sodium methoxide in MeOH (97 ml, 48.3 mmol) at RT for 3 hour. It was filtered and the filtrate was concentrated under reduced pressure. The residue was washed with water and dried to give compound J2 (9.79 g). LCMS for J2: m/e = 203 (M+l).

Reference:
Patent; MERCK SHARP & DOHME CORP.; WU, Wen-Lian; HE, Shuwen; WALSH, Shawn, P.; CUMMING, Jared, N.; (70 pag.)WO2016/118404; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

8-Sep-2021 News The origin of a common compound about 330786-09-9

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.

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. 330786-09-9, name is Methyl 3,5-dichloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., HPLC of Formula: C6H4Cl2N2O2

b) Synthesis of 3-chloro-5-morpholin-4-yl-pyrazine-2-carboxylic acid methyl ester To a solution of 3,5-dichloro-pyrazine-2-carboxylic acid methyl ester (1.20 g, 5.82 mmol) in dimethylformamide (12 ml) is added potassium carbonate (0.96 g, 6.98 mmol) at RT followed by the addition of morpholine (0.5 ml, 5.82 mmol). The resulting mixture is stirred at RT for 3 h. After completion of the reaction, the mixture is diluted with water (20 ml) and extracted with EtOAc (3*30 ml). The combined organic layers are washed with water (30 ml), brine (30 ml), dried over anhydrous sodium sulfate and evaporated in vacuo to get the crude product, which is purified by column chromatography (silica gel, 10% acetone/hexane) to yield 3-chloro-5-morpholin-4-yl-pyrazine-2-carboxylic acid methyl ester (1.10 g, 4.28 mmol, 73%).

Reference:
Patent; GRUeNENTHAL GMBH; LUCAS, Simon; Kuehnert, Sven; Bahrenberg, Gregor; Schroeder, Wolfgang; US2014/148454; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

The origin of a common compound about 330786-09-9

Methyl 3,5-dichloropyrazine-2-carboxylate (5.0 g, 24.2 mmol) was dissolved in a 9: 1 mixture of dry tetrahydrofuran (242 mL) and methanol (27 mL). The mixture was cooled to 1.5-2 C with an ice/water bath and stirred at this temperature for 10 min. A 2 M solution of lithium borohydride in THF (13.3 mL, 26.6 mmol) was then added carefully keeping the temperature below 4-5 C. After addition, the reaction mixture was stirred for an additional 10-15 min at 0-4 C. Methanol (120 mL) was added to the flask and the mixture stirred for 15 min at rt. The reaction was slowly poured into a mixture of 1 M HC1 solution (100 mL) and ethyl acetate (200 mL). The resulting mixture was stirred at rt for 15 min. The aqueous layer was extracted with ethyl acetate (3 x 150 mL) and the combined organics washed with brine (2 x 100 mL), dried over anhydrous MgS04, filtered, and concentrated under reduced pressure. (3,5-Dichloropyrazin-2-yl)methanol (4.3 g, 99% yield) was obtained as a yellow oil after drying under high vacuum for 2 h. 1H-NMR (500 MHz, CDCI3) d 8.52 (s, 1H), 4.85 (s, 2H).

Reference:
Patent; RELAY THERAPEUTICS, INC.; D.E. SHAW RESEARCH, LLC; TAYLOR, Alexander, M.; LESCARBEAU, Andre; KELLEY, Elizabeth, H.; SHORTSLEEVES, Kelley, C.; WALTERS, W., Patrick; MURCKO, Mark, Andrew; MCLEAN, Thomas, H.; GUNAYDIN, Hakan; GIORDANETTO, Fabrizio; THERRIEN, Eric; (607 pag.)WO2019/183367; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Continuously updated synthesis method about 330786-09-9

The synthetic route of 330786-09-9 has been constantly updated, and we look forward to future research findings.

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. 330786-09-9, name is Methyl 3,5-dichloropyrazine-2-carboxylate belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: Methyl 3,5-dichloropyrazine-2-carboxylate

The mixture of methyl 3,5-dichloropyrazine-2-carboxylate (1.0 g, 4.83 mmol), (3L’)- l,3-dihydrospiro[indene-2,4′-piperidin]-3-amine dihydrochloride (1.65 g, 4.83 mmol, Intermediate I) and CsF (3.66 g, 24.1 mmol) in DMF (15 mL) was stirred at 70 C for 2 hours. BOC20 (1.57 g, 7.24 mmol) and TEA (1 mL) were added to the mixture and the mixture was stirred at 20 C for 1 hour. The mixture was diluted with H20 (50 mL), extracted with EtOAc (50 mL x 2). The organic layer was washed with brine (50 mL), dried over anhydrous Na2S04, filtered and concentrated under reduced pressure and the residue was purified by column chromatography (petroleum ether / ethyl acetate = 1 : 0 ~ 5 : 1) to afford methyl 5-[(3ri)-3-{[(/er/-butoxy)carbonyl]amino}-l,3-dihydrospiro[indene-2,4′-piperidin]-r- yl]-3-chloropyrazine-2-carboxylate (1.58 g, 69% yield) as a yellow solid and methyl 3-[(3L’)- 3-{[(/er/-butoxy)carbonyl]amino}-l,3-dihydrospiro[indene-2,4′-piperidin]-l’-yl]-5- chloropyrazine-2-carboxylate (320 mg, 14% yield) as a yellow solid. LCMS m/z (M+H)+ = 473.1 for both isomers.

The synthetic route of 330786-09-9 has been constantly updated, and we look forward to future research findings.

Extended knowledge of 330786-09-9

Statistics shows that Methyl 3,5-dichloropyrazine-2-carboxylate is playing an increasingly important role. we look forward to future research findings about 330786-09-9.

Reference of 330786-09-9, These common heterocyclic compound, 330786-09-9, name is Methyl 3,5-dichloropyrazine-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.

To a solution of 3,5-dichloro-pyrazine-2-carboxylic acid methyl ester (1.20 g, 5.82 mmol) in dimethylformamide (12 ml) is added potassium carbonate (0.96 g, 6.98 mmol) at RT followed by the addition of morpholine (0.5 ml, 5.82 mmol). The resulting mixture is stirred at RT for 3 h. After completion of the reaction, the mixture is diluted with water (20 ml) and extracted with EtOAc (3 x 30 ml). The combined organic layers are washed with water (30 ml), brine (30 ml), dried over anhydrous sodium sulfate and evaporated in vacuo to get the crude product, which is purified by column chromatography (silica gel, 10% acetone/hexane) to yield 3-chloro-5-morpholin-4-yl-pyrazine-2-carboxylic acid methylester (1.10 g, 4.28 mmol, 73%).

Statistics shows that Methyl 3,5-dichloropyrazine-2-carboxylate is playing an increasingly important role. we look forward to future research findings about 330786-09-9.

Reference:
Patent; GRUeNENTHAL GMBH; LUCAS, Simon; KUHNERT, Sven; BAHRENBERG, Gregor; SCHROeDER, Wolfgang; WO2014/82739; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Extended knowledge of C6H4Cl2N2O2

At 0 C. a solution of 12 (2.59 g) and NEt3 (1.744 ml) in DMF (20 ml), was added to a solution of 6 (2.95 g) in DMF (5 ml) and stirred for 16 h at 25 C. The mixture was diluted with ethyl acetate (70 ml) and washed with water (50 ml). The aqueous phase was extracted with ethyl acetate (30 ml), the combined organic phases washed with brine, dried over Na2SO4 and the solvent evaporated. Chromatography on silica (gradient cyclohexane/ethyl acetate) gave 13 (950 mg) as a yellow solid. UPLC/MS found for C17H25ClN4O4 as (M+1)+ 385.0, UPLC retention time 1.03 min.

Reference:
Patent; NOVARTIS AG; Thoma, Gebhard; Smith, Alexander Baxter; van Eis, Maurice; US2013/310387; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

New downstream synthetic route of 330786-09-9

To a solution of methyl 3,5-dichloropyrazine-2-carboxylate (0.312 g, 1.51 mmol) in THF (4.5 mL) at RT was added sodium hydride (60% wt. dispersion, 0.199 g, 4.98 mmol) and methanol (0.200 mL, 4.94 mmol). The reaction mixture was stirred at RT for 30 min, diluted with EtOAc, and quenched with saturated NH4C1. The reaction mixture was partitioned between brine and EtOAc. The aqueous phase was extracted with EtOAc (3 x) and the combined organic extracts were washed with brine (1 x), dried over MgS04, filtered, and concentrated. Purification by flash column chromatography on silica gel (10% to 50% EtOAc in hexanes) gave ethyl 3,5-dimethoxypyrazine-2-carboxylate (0.314 g, 1.48 mmol, 98% yield) as an off white solid. LC/MS (ESf ) m/z = 199.1 (M+H)+

Reference:
Patent; AMGEN INC.; MINATTI, Ana Elena; LOW, Jonathan, D.; ALLEN, Jennifer, R.; AMEGADZIE, Albert; BROWN, James; FROHN, Michael, J.; GUZMAN-PEREZ, Angel; HARRINGTON, Paul, E.; LOPEZ, Patricia; MA, Vu Van; NISHIMURA, Nobuko; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert, M.; SHAM, Kelvin; SMITH, Adrian, L.; WHITE, Ryan; XUE, Qiufen; WO2014/138484; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Continuously updated synthesis method about 330786-09-9

The mixture of methyl 3,5-dichloropyrazine-2-carboxylate (1.0 g, 4.83 mmol, CAS 330786-09-9), (3ri)-l,3-dihydrospiro[indene-2,4′-piperidin]-3-amine dihydrochloride (1.65 g, 4.83 mmol, Intermediate I) and CsF (3.66 g, 24.1 mmol) in DMF (15 mL) was stirred at 70 C for 2 hours. Boc20 (1.57 g, 7.24 mmol) and TEA (1 mL) were then added to the mixture and the mixture was stirred at 20 C for 1 hour. The mixture was diluted with H20 (50 mL), and extracted with EtOAc (50 mL x 2). The organic layer was washed with brine (50 mL), dried over anhydrous Na2S04, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether / ethyl acetate = l : 0 ~ 5 : l) to afford methyl 5-[(3ri)-3-{[(/er/-butoxy)carbonyl]amino}-l,3-dihydrospiro[indene-2,4′- piperidin]-l’-yl]-3-chloropyrazine-2-carboxylate (1.58 g, 69% yield) as a yellow solid. LCMS m/z [M+H]+ = 473.1.

Some tips on C6H4Cl2N2O2

The chemical industry reduces the impact on the environment during synthesis Methyl 3,5-dichloropyrazine-2-carboxylate. I believe this compound will play a more active role in future production and life.

Electric Literature of 330786-09-9, 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. 330786-09-9, name is Methyl 3,5-dichloropyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of methyl 3,5-dichloropyrazine-2-carboxylate (100 mg, 0.483 mmol) in dioxane (1.93 mL) were added tert-butyl (4-methylpiperidin-4-yl)carbamate (109 mg, 0.507 mmol) and TEA (0.141 mL, 1.01 mmol) and the resulting mixture was stirred at 24 C for 18 h. H20 (20 mL) was added, and the layers were separated. The aqueous phase was extracted with EtOAc (3 x 20 mL), the combined organic layers were washed with sat NaCl, dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified via silica gel chromatography (0 – 100 % EtOAc in hexanes) to give the title compound (120 mg, 64%) as pale yellow solid. MS (ES+) C17H25CIN4O4 requires: 384, found: 407 [M+Na]+. ‘H NMR (500 MHz, Chloroform-c d 7.88 (s, 1H), 4.40 (s, 1H), 3.96 (s, 3H), 3.71 – 3.57 (m, 2H), 3.46 – 3.27 (m, 2H), 2.19 – 2.04 (m, 2H), 1.74 – 1.62 (m, 2H), 1.54 – 1.34 (m, 12H). Also isolated regioisomer methyl 5-(4-((tert-butoxycarbonyl)amino)-4-methylpiperidin-l-yl)-3- chloropyrazine-2-carboxylate (60 mg, 32%) as a pale yellow solid. 1 H NMR (500 MHz, Chloroform-c ) d 8.03 (s, 1H), 4.41 (s, 1H), 4.06 – 3.96 (m, 2H), 3.95 (s, 3H), 3.53 – 3.39 (m, (0708) 2H), 2.26 – 2.12 (m, 2H), 1.72 – 1.57 (m, 2H), 1.50 – 1.37 (m, 12H).

Reference:
Patent; BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM; JONES, Philip; CROSS, Jason; BURKE, Jason; MCAFOOS, Timothy; KANG, Zhijun; (154 pag.)WO2019/213318; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

The origin of a common compound about 330786-09-9

Reference:
Patent; GRUeNENTHAL GMBH; LUCAS, Simon; Kuehnert, Sven; Bahrenberg, Gregor; Schroeder, Wolfgang; US2014/148454; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem