Day: April 19, 2022

Reference of 124236-37-9 ,Some common heterocyclic compound, 124236-37-9, molecular formula is C8H6F3NO2, 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 mixture of 5-(trifluoromethyl)-pyridine-2-carboxylic acid methyl ester (2.7 g, 13 mmol) and m-CPBA (CAN 937-14-4, 6.7 g, 39 mmol) in dry methylene chloride (30 mL) was stirred under reflux conditions overnight. Removal of the solvent in vacuo and purification of the obtained residue by column chromatography (silica gel, 15 g, 20% ethyl acetate in petroleum ether) provided the title compound (2.2 g, 76%) as light-yellow solid; MS (EI): m/e = 222.1 [M+H]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,124236-37-9, its application will become more common.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; BISSANTZ, Caterina; GRETHER, Uwe; HEBEISEN, Paul; KIMBARA, Atsushi; LIU, Qingping; NETTEKOVEN, Matthias; PRUNOTTO, Marco; ROEVER, Stephan; ROGERS-EVANS, Mark; SCHULZ-GASCH, Tanja; ULLMER, Christoph; WANG, Zhiwei; YANG, Wulun; WO2012/168350; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 695-98-7, 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 695-98-7 as follows.

In dichloromethane (15.0 ml), 2,3,5-trimethyl-pyridine (1.29 g) was dissolved. The reaction solution was cooled to 0°C and added with meta-chloroperbenzoic acid (2.53 g), followed by stirring at room temperature for 1.5 hours. The reaction solution was added with a 1 mol/l sodium hydroxide aqueous solution and then subjected to extraction with chloroform. Subsequently, the organic layer was washed with saturated saline solution and dried with anhydrous sodium sulfate. The drying agent was filtrated out and the solvent was then distilled off, followed by dissolving the resulting residue in dichloromethane (25.0 ml). The reaction solution was added with trifluoroacetic anhydride (2.8 ml) and subjected to thermal reflux for 3.5 hours. After the reaction solution had been cooled to room temperature, the solvent was distilled off. The residue obtained was dissolved in methanol (60.0 ml). After having been cooled to 0°C, the reaction solution was added with a 12.5percent sodium methoxide/methanol solution to adjust to pH 10, followed by stirring at room temperature for 16.5 hours. After the solvent had been distilled off, the residue was added with distilled water and extracted with chloroform. The organic layer was washed with saturated saline solution and dried with anhydrous sodium sulfate. The drying agent was filtrated out and the solvent was then distilled off, followed by dissolving the resulting residue in chloroform (30.0 ml). The reaction solution was added with manganese dioxide (chemically processed product) (6.10 g) and then stirred at room temperature for 18 hours. The reaction solution was filtrated through Celite. The solvent in the filtrate was distilled off and the residue obtained was then purified through silica gel column chromatography (chloroform/ethyl acetate), thereby obtaining the subject compound (1.14 g) as a yellow oily substance. MS(FAB,Pos.):m/z=136[M+H]+1H-NMR(500MHz,CDCl3):delta=2.40(3H,s),2.63(3H,s),7.43(1H,brs),8.48(1 H,brs),10.16(1H,s).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,695-98-7, its application will become more common.

Reference:
Patent; Kureha Chemical Industry Co., Ltd.; EP1550657; (2005); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 880870-13-3, 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. 880870-13-3, name is 5-Bromo-2-chloro-4-methoxypyridine. A new synthetic method of this compound is introduced below.

A solution of 5-bromo-2-chloro-4-methoxypyridine (5.0 g, 22.48 mmol) in DMF (80 mL) was purged with nitrogen for 15 minutes. At this point, Zn(CN)2 (3.96 g, 33.7 mmol) andPd(Ph3P)4 (2.60 g, 2.25 mmol) were added, successively. The resulting suspension was stirred at 95 C for 12 hours under nitrogen atmosphere. The reaction mixture was cooled to ambient temperature, and filtered to remove inorganic solid. The solvent (DMF) was evaporated to provide the crude residue as an oil, which was purified on silica gel and eluted with 0-30% ethyl acetate / hexanes to afford the product.? NMR (500 MHz, DMSO-<¾), delta 8.69 (s, 1H), 7.50 (s, 1H), 4.04 (s, 3H); LC/MS (M+l)+ = 169. At the same time, in my other blogs, there are other synthetic methods of this type of compound,880870-13-3, 5-Bromo-2-chloro-4-methoxypyridine, and friends who are interested can also refer to it. Reference:
Patent; MERCK SHARP & DOHME CORP.; WALSH, Shawn, P.; PASTERNAK, Alexander; DEJESUS, Reynalda, K.; TANG, Haifeng; PIO, Barbara; SHAHRIPOUR, Aurash; BELYK, Kevin, M.; CHOBANIAN, Harry, R.; GUO, Yan; FRIE, Jessica, L.; SHI, Zhi-Cai; CHEN, Helen; BLIZZARD, Timothy, A.; CATO, Brian; WO2013/66714; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 52605-96-6, With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.52605-96-6, name is 2-Chloro-3-methoxypyridine, molecular formula is C6H6ClNO, molecular weight is 143.57, as common compound, the synthetic route is as follows.

To a solution of Compound 4 (100 mg) in 2-propanol (5 ml) were added 2-chloro-3-methoxy pyridine (182 mg) and concentrated sulfuric acid (165 mg). It was stirred under refluxing for 48 hours. The solvent was removed under reduced pressure. Saturated sodium bicarbonate solution and water were added to the residue. The mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo. The obtained residue was purified by column chromatography. The obtained solid was recrystallized with diethylether-hexane to give Compound I-17 (76.8 mg).1H-NMR (CDCl3) delta: 1.70 (3H, s), 3.88 (3H, s), 4.65 (2H, br), 6.23-6.33 (2H, m), 6.66 (1H, dd, J=10.2, 5.2 Hz), 6.91-7.02 (3H, m), 7.43 (1H, dd, J=7.1, 2.9 Hz), 7.78 (1H, dd, J=5.0, 1.3 Hz), 7.84-7.91 (1H, m)

Statistics shows that 52605-96-6 is playing an increasingly important role. we look forward to future research findings about 2-Chloro-3-methoxypyridine.

Reference:
Patent; SHIONOGI & CO., LTD.; US2012/238557; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 74936-72-4, With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.74936-72-4, name is 5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid, molecular formula is C16H16N2O6, molecular weight is 332.31, as common compound, the synthetic route is as follows.

(1) Preparation of (R)-5-(methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid To a solution of 5-(methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (700 g, 2.1 mol) in methanol (14 L) was added Quinidine (617 g, 1.90 mol). The mixture was stirred at 90 C. under reflux until Quinidine was completely dissolved. The stirring was continued for 3 hours. 4.5 L water was added. The stirring was continued for half an hour. The mixture was cooled down slowly. A solid was precipitated out and was filtered. The filter cake was treated with hydrochloric acid to produce (R)-5-(methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (130 g) in a yield of 18.6%.

Statistics shows that 74936-72-4 is playing an increasingly important role. we look forward to future research findings about 5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid.

Reference:
Patent; XUANZHU PHARMA CO., LTD.; Zhang, Hui; Fan, Mingwei; Sun, Liang; US2014/45896; (2014); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 54232-43-8, The major producers of chemicals have been the Europe, Japan and China. Due to the growing call for a cleaner, greener environment, people will have to find innovative ways to maintain their relevance. Here is a compound 54232-43-8, name is 6-Bromo-5-methoxypicolinic acid. This compound has unique chemical properties. The synthetic route is as follows.

A mixture of 6-bromo-5-methoxy-pyridine-2-carboxylic acid (0.3 g, 1 mmol), 3-chlorophenylboronic acid (CAN 63503-60-6, 0.23 g, 1 mmol), tris(dibenzylidene-acetone)-dipalladium(0) (CAN 52409-22-0, 0.12 g), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (CAN 161265-03-8, 0.15 g) and potassium carbonate (0.21 g, 2 mmol) in 1,4-dioxane (10 mL) was stirred for 12 h at 110 C. under a nitrogen atmosphere. The reaction mixture was filtered, concentrated under reduced pressure and purified by column chromatography (silica gel, 10 g, eluting with 10% methanol in methylene chloride) to give the title compound (0.1 g, 29%); MS (EI): m/e=264.0 [M+H]+.

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant.we look forward to future research findings about 54232-43-8, 6-Bromo-5-methoxypicolinic acid.

Reference:
Patent; Bissantz, Caterina; Grether, Uwe; Hebeisen, Paul; Kimbara, Atsushi; Liu, Qingping; Nettekoven, Matthias; Prunotto, Marco; Roever, Stephan; Rogers-Evans, Mark; Schulz-Gasch, Tanja; Ullmer, Christoph; Wang, Zhiwei; Yang, Wulun; US2012/316147; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – 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. 327056-62-2, name is 2-Cyano-5-fluoropyridine, the common compound, a new synthetic route is introduced below. HPLC of Formula: C6H3FN2

Example 32.2-(6-Fluoro-imidazo[l ,5-a]pyridin-l -yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3- cyano-azetidin- 1 -yl)- 1 -methyl-2- xo-ethyl]-amideStep 1(5 -Fluoro-pyridin-2-yl)-meth lamineIn a Parr pressure bottle, 2-cyano-5-fluoropyridine (2.0 g, 16.4 mmol) was dissolved in ethanol (60 ml). Palladium on carbon, 10% Pd (wet) (574 mg, 5.39 mmol) was added followed by cone. HC1 (4.6 ml, 56.0 mmol). The bottle was placed on a Parr hydrogenator and shaken for 3.5 h under a 45 psi hydrogen atmosphere. The reaction mixture was filtered over Celite and rinsed with methanol. The filtrate was concentrated to a light yellow solid. The solid was taken up in dichloromethane, cooled to 0C, and basified with saturated aqueous NaHC03. The aqueous layer was extracted with dichloromethane (3x) and the combined organics were dried over sodium sulfate, filtered and concentrated to give 558 mg (27%) of (5-fluoro-pyridin-2-yl)- methylamine as a yellow oil which was used without further purification.

The synthetic route of 327056-62-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; CHEN, Shaoqing; DE VICENTE FIDALGO, Javier; HAMILTON, Matthew Michael; HERMANN, Johannes Cornelius; KENNEDY-SMITH, Joshua; LI, Hongju; LOVEY, Allen John; LUCAS, Matthew C.; LUK, Kin-Chun Thomas; LYNCH, Stephen M.; O’YANG, Counde; PADILLA, Fernando; SCHOENFELD, Ryan Craig; SIDDURI, Achyutharao; SOTH, Michael; WANG, Ce; WOVKULICH, Peter Michael; ZHANG, Xiaohu; WO2013/30138; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 33252-28-7, 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. 33252-28-7, name is 6-Chloronicotinonitrile, molecular formula is C6H3ClN2, The 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.

N-[4-(5-Cyano-2-methoxy-pyridin-3-yl)-benzyl]-2-trifluoromethoxy-benzenesulfonamide To a solution of 4-aminomethylphenylboronic acid hydrochloride (2.0 g, 13.2 mmol) in methanol (20 ml) was added di-tert-butyl dicarbonate (3.16 g, 15.5 mmol) and sodium bicarbonate (3.32 g, 19.8 mmol). The mixture was sonicated for 4 h then concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over anhydrous magnesium sulfate and the solvent evaporated to give (4-bromo-benzyl)-carbamic acid tert-butyl ester (1.8 g, 13.2 mmol, 100%) as a white solid. To 6-chloro-nicotinonitrile (15 g, 0.11 mol) under argon atmosphere was added 25% sodium methoxide in methanol (11.7 g, 0.22 mol) and the mixture heated under reflux for 20 h. The methanol was evaporated and the residue partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried over anhydrous magnesium sulfate and the solvent evaporated to give 6-methoxy-nicotinonitrile (17.0 g, 0.13 mol, 117%) as a white solid. To 6-methoxy-nicotinonitrile (13.2 g, 99 mmol) in acetic acid (32 ml) was added sodium acetate (8.1 g, 99 mmol). The mixture was stirred and a solution of bromine (31.5 g, 197 mmol) in acetic acid (32 ml) added. The mixture was heated to 80 C. for 48 h. The reaction mixture was poured into water and extracted with diethyl ether. The organic phase was washed with 4M aqueous sodium hydroxide solution, 5% sodium thiosulfate solution, dried over anhydrous potassium carbonate and the solvent was evaporated to give 5-bromo-6-methoxy-nicotinonitrile (11.9 g, 56 mmol, 57%). To a solution of 2-methoxy-5-cyanopyridine-3-boronic acid (1.0 g, 4.0 mmol) in 1,2-dimethoxyethane (10 ml) was added (4-bromo-benzyl)-carbamic acid tert-butyl ester (0.42 g, 2.0 mmol), tetrakis(triphenylphosphine)palladium (0) (114 mg, 0.1 mmol) and 2M aqueous sodium carbonate (1 ml, 2.0 mmol). The reaction was heated to 150 C. for 10 min in a microwave over. The mixture was concentrated under reduced pressure and partitioned between ethyl acetate and water. The organic phase was washed with water, then brine, dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified on silica gel eluting with 5:1 heptane/ethyl acetate to give [4-(5-cyano-2-methoxy-pyridin-3-yl)-benzyl]-carbamic acid tert-butyl ester as a white solid (0.5 g, 1.47 mmol, 37%). To a solution of [4-(5-cyano-2-methoxy-pyridin-3-yl)-benzyl]-carbamic acid tert-butyl ester (0.5 g, 1.5 mmol) in dichloromethane (5 ml) at 0 C. was added trifluoroacetic acid (5 ml, 28 mmol). The reaction mixture was stirred for 30 min at 0 C. before the solvent was evaporated and the residue purified on a SCX column (eluted with 2M ammonia in methanol) to give 5-(4-aminomethyl-phenyl)-6-methoxy-nicotinonitrile as a clear glass (0.39 g, 1.6 mmol, 107%). To a solution of 5-(4-aminomethyl-phenyl)-6-methoxy-nicotinonitrile (57.3 mg, 0.24 mmol) in dichloromethane (2 ml) was added triethylamine (73.0 mg, 0.72 mmol) and 2-(trifluoromethoxy)benzenesulfonyl chloride. The reaction mixture was agitated for 20 hours and the solvent evaporated under reduced pressure. The crude product was taken up in dimethyl sulfoxide (1 ml) and purified by preparatory LCMS. The solvent was evaporated under reduced pressure to give the title compound (19.1 mg, 0.04 mmol, 17%). 1H NMR (400 MHz, DMSO-d6): delta 8.68 (d, 1H), 8.47 (t, 1H), 8.15 (d, 1H), 7.90 (m, 1H), 7.73 (m, 1H), 7.45-7.55 (m, 4H), 7.31 (d, 2H), 4.19 (d, 2H), 3.96 (s, 3H) ppm; MS (ESI) m/z: 464.3 [M+H]+.

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant.we look forward to future research findings about 33252-28-7, 6-Chloronicotinonitrile.

Reference:
Patent; N.V. Organon; Pharmacopeia Drug Discovery Inc.; US2007/149577; (2007); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – 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. 17570-98-8, name is 2-(Bromoacetyl)pyridine hydrobromide, molecular formula is C7H7Br2NO, The 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. category: pyridine-derivatives

Example 8; (S)-(4-Fluoro-phenyl)(3-(4-(pyridin-2-yl)-oxazol-2-yl)-piperidin-l-yl)-methanone; A solution of (S)-I -(4-fluoro-benzoyl)-piperidine-3-carboxylic acid amide (0.2 g, 0.8 mmol), prepared as described in Example l(C), and 2-(bromoacetyl)-pyridine hydrobromide (90 mg, 0.32 mmol) in dry N-methyl-2-pyrrolidinone (2.5 mL) was heated at 1000C for 5 h. The reaction mixture was cooled to room temperature, ethyl acetate was added and the organic layer was washed sequentially with water (twice) and with brine (twice). The organics were dried over sodium sulphate and evaporated under reduced pressure to afford a crude oil that was purified by flash chromatography: after 3 successive column chromatography purifications (silica gel, eluent: DCM/MeOH/NH4OH 98:2:0.2), 18 mg of (S)-(4-Fluoro-phenyl)(3-(4- (pyridin-2-yl)-oxazol-2-yl)-piperidin-l-yl)-methanone were obtained as a brown oil. Yield: 16%; LCMS (RT): 1.99 min (Method H); MS (ES+) gave m/z: 352.2 (MH+). 1H-NMR (DMSO-d6 353K), delta (ppm): 8.57 (ddd, IH) 8.43 (s, IH) 7.77-7.88 (m, 2H) 7.43-7.50 (m, 2H) 7.28-7.33 (m, IH) 7.19-7.27 (m, 2H) 4.21 (dd, IH) 3.78 (dd, IH) 3.46 (dd, IH) 3.13-3.35 (m, 2H) 2.15-2.28 (m, IH) 1.78-2.01 (m, 2H) 1.52-1.70 (m, IH).

With the rapid development of chemical substances, we look forward to future research findings about 17570-98-8.

Reference:
Patent; ADDEX PHARMA S.A.; WO2008/56259; (2008); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 63237-88-7, The major producers of chemicals have been the Europe, Japan and China. Due to the growing call for a cleaner, greener environment, people will have to find innovative ways to maintain their relevance. Here is a compound 63237-88-7, name is Pyrazolo[1,5-a]pyridine-2-carboxylic acid. This compound has unique chemical properties. The synthetic route is as follows.

Example 97N-((ls,4s)-4-(2-(4′-(((3S,5R)-3,5-dimethylpiperazin-l-yl)methyl)-3′-hydroxybiphenyl-3- yloxyJ-S-fluoronicotinamidoJcyclohexylJpyrazolo [ 1 ,5-a] pyridine-2-carboxamide To a solution of pyrazolo[l,5-a]pyridine-2-carboxylic acid (30.8 mg, 0.19 mmol) in acetonitrile (3 mL) was added DIPEA (0.066 mL, 0.38 mmol). To this mixture was then added HATU (72.3 mg, 0.19 mmol). The mixture was stirred at RT for 10 min before it was added to a solution of N-((ls,4s)-4-aminocyclohexyl)-2-(4′-(((3S,5R)-3,5-dimethylpiperazin- l-yl)methyl)-3′-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamide, hydrochloride (125 mg, 0.19 mmol) and DIPEA (0.066 mL, 0.38 mmol) in acetonitrile (3 mL). The mixture was stirred at RT overnight. 1 mL water and 1 mL acetic acid was then added to the mixture before being purified using reverse phase preparative HPLC (eluent = TFA(aq)/MeCN). The appropriate fractions were combined and evaporated to give a residue. This was triturated with ether to give the title compound as a solid which was isolated by filtration and dried overnight under vacuum at 400C. Yield: 96 mg 1H NMR (400 MHz, CD3OD) delta 8.48 (d, J = 7.4 Hz, IH), 8.43 (d, J = 7.2 Hz, IH), 8.12 (d, J = 3.1 Hz, IH), 8.06 (dd, J = 7.9, 3.1 Hz, IH), 7.66 (d, J = 9.0 Hz, IH), 7.51 – 7.43 (m, 2H), 7.40 – 7.37 (m, IH), 7.25 – 7.17 (m, 3H), 7.10 – 7.07 (m, 2H), 6.97 – 6.93 (m, 2H), 4.17 – 4.11 (m, IH), 4.07 (s, IH), 4.04 – 3.99 (m, IH), 3.58 – 3.51 (m, 2H), 3.45 – 3.40 (m, 2H), 2.64 (t, J = 12.6 Hz, 2H), 1.92 – 1.70 (m, 8H), 1.31 (d, J = 6.4 Hz, 6H). MS: [M+H]+=692.2 (calc=692.336) (MultiMode+)

According to the analysis of related databases, 63237-88-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2009/144494; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem