Pyridine-derivatives

Electric Literature of 115309-58-5, Adding some certain compound to certain chemical reactions, such as: 115309-58-5, name is N-(tert-Butyl)-6-chloronicotinamide,molecular formula is C10H13ClN2O, 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 115309-58-5.

The intermediate A-1 (1.0 g, 4.7 mmol) was dissolved in 15 ml of tetrahydrofuran and the reaction mixture was cooled to 0 C. O-methylphenylmagnesium chloride (1M in tetrahydrofuran solution, 14.1 mL, 14.1 mmol) was slowly added, and the reaction was kept for 3 hours, then heated to 30 C for 18 h, and then cooled to 0 C. Glacial acetic acid (24 mmol) was slowly added dropwise, and then DDQ (dichlorodicyanobenzoquinone or manganese acetate) (1.6 g, 7.1 mmol) was added to react at room temperature for 1 h.The reaction solution was poured into a 2M sodium carbonate solution, extracted with ethyl acetate, washed with water and brine, and dried over anhydrous sodium sulfate.After concentration under reduced pressure, it was purified by silica gel column chromatography.Ethyl acetate/petroleum ether (1:1) was used as the mobile phase to give intermediate A-2.The yield of pale yellow solid was 88%.

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. 115309-58-5, N-(tert-Butyl)-6-chloronicotinamide, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Beijing Kuanhou Pharmaceutical Technology Co., Ltd.; Cui Yimin; He Long; Ouyang Liang; Gou Maling; Wang Ling; (39 pag.)CN109384712; (2019); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 91940-84-0, 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 91940-84-0, name is 2-(tert-Butyl)isonicotinic acid. This compound has unique chemical properties. The synthetic route is as follows.

Step 3: Preparation of benzyl (1R,3R,5R)-2-(2-(tert-butyl)isonicotinoyl)-2-azabicyclo[3.1.0]hexane-3-carboxylate Benzyl (1R,3R,5R)-2-azabicyclo[3.1.0]hexane-3-carboxylate hydrochloride (0.450 g, 1.36 mmol), O-(Benzotriazol-1-yl)-N,N,N’N’-tetramethyluronium hexafluorophosphate (0.78 g, 2.04 mmol), benzotriazol-1-ol (0.28 g, 2.04 mmol) and 2-(tert-butyl)isonicotinic acid (0.269 g, 1.50 mmol) were added to a flask and NMP (5.0 mL) was added, followed by N,N-diisopropylethylamine (0.71 mL, 4.08 mmol). The resulting mixture was stirred at 22 C. for 20 minutes. The reaction was diluted with EtOAc (60 mL) and saturated NaHCO3 (70 mL) solution. The layers were shaken vigorously and the organic phase was washed again with saturated NaHCO3 solution, twice with water, and once with saturated sodium chloride solution. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. The remaining viscous oil was purified by MPLC using silica gel and eluted with a gradient of 0-30% EtOAc/hexanes, providing benzyl (1R,3R,5R)-2-(2-(tert-butyl)isonicotinoyl)-2-azabicyclo[3.1.0]hexane-3-carboxylate (0.386 g, 1.02 mmol) as a colorless glassy solid. LCMS-APCI (POS.) m/z: 379.2 (M+H)+.

According to the analysis of related databases, 91940-84-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AMGEN INC.; CYTOKINETICS, INC.; Ashcraft, Luke; Boezio, Alessandro; Butler, John; Chandra, Aroop; Chuang, Chihyuan; Collibee, Scott E.; Debenedetto, Mikkel; DiMassa, Vincent; Graceffa, Russell; Malinowski, Justin; Moebius, David; Morgan, Bradley P.; Payette, Joshua; Romero, Antonio; St. Jean, JR., David; Vargas, Richard; Yeoman, John; Zhang, Hanmo; (146 pag.)US2019/77793; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 64119-42-2, 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. 64119-42-2, name is Ethyl 6-chloro-5-cyano-2-methylpyridine-3-carboxylate. A new synthetic method of this compound is introduced below.

(c) Ethyl 6-[4-(5-benzyI-4eta-l,2,4-triazol-3-yl)piperidin-l-yl]-5-cyano-2- methylnicotinateEthyl 6-chloro-5-cyano-2-methyhiicotinate (225 mg, 1.0 mmol)) and the crude 4-(5- benzyl-4H-l,2,4-triazol-3-yl)piperidine (267 mg, 1.1 mmol) were dissolved in EtOH (10 ml) and DIPEA (1 ml) was added. The reaction mixture was heated to 120 0C for 5 min.LCMS showed product and the 1,3, 4- oxadiazole byproduct. NaHCO3 (aq) was added and the mixture was extracted with dichloromethane (x3). The combined organic layer was run through a phase separator and evaporated. The crude product was purified by prepHPLC [Kromasil C8, Gradient: 30 to 60 % (CH3CN/0.1M NH4AcO(aq), pH = 7)] giving ethyl 6-[4-(5-benzyl-4H-l,2,4-triazoltau3-yl)piperidin-l-yl]-5-cyano-2-methyhiicotinate. Yield:38mg (9 % over 3 steps). The 1,3, 4- oxadiazole was not isolated.1HNMR (500MHz, DMSOd6): 1.32 (3H, t, J=7.1Hz), 1.72-1.81 (2H, m), 2.03-2.08 (2H, m), 2.66 (3H, s), 3.05-3.15 (IH, m), 3.29-3.32 (2H, m), 3.99 (2H, s), 4.27 (2H, q, J=7.1), 4.55-4.61 (2H, m), 7.20-7.24 (IH, m), 7.26-7.33 (4H, m), 8.35 (IH, s), 13.45 (IH, br s).MS m/z: 431 (M+l), 429 (M-I).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,64119-42-2, Ethyl 6-chloro-5-cyano-2-methylpyridine-3-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; ASTRAZENECA AB; WO2008/4942; (2008); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 63071-09-0 ,Some common heterocyclic compound, 63071-09-0, molecular formula is C7H9NO, 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.

Commercially available 2,3-lutidine (5.00 g) was dissolved in dichloromethane (50 ml) and the solution was cooled to 0C. After that, the solution was added with meta-chloroperbenzoic acid (12.1 g) and then stirred at room temperature for 2 hours. After completion of the reaction, the solution was added with dichloromethane and washed with a 1 mol/l sodium hydroxide aqueous solution and saturated saline solution, followed by drying with anhydrous sodium sulfate. Then, the solvent was distilled off, thereby obtaining crude 2,3-lutidin-N-oxide (3.16 g). A 2.00 g part thereof was dissolved in dichloromethane (40 ml) and then the solution was cooled to 0C. Subsequently, the solution was added with trifluoroacetic anhydride (4.49 ml), followed by stirring at room temperature for 4 hours and then at 45C for 3 hours. After completion of the reaction, the solvent was distilled off and the residue was dissolved in methanol (30 ml), followed by the addition of a sodium methoxide/methanol solution until the pH of the solution would reach pH = 10. After the solution had been stirred at room temperature for 1 hour, the solvent was distilled off and extraction was then carried out with dichloromethane. The extract was dried with anhydrous sodium sulfate and the solvent was then distilled off, thereby obtaining 3-methyl-2-hydroxymethylpyridine (1.30 g). A 605.3 mg part thereof was dissolved in chloroform (30 ml) and then added with manganese dioxide (chemically processed product) (3.03 g), followed by stirring at 70C for 2 hours. After completion of the reaction, the catalyst was removed through Celite filtration and the solvent was then concentrated. Then, the residue was purified through silica gel column chromatography (chloroform/ethyl acetate), thereby obtaining the subject compound (419.8 mg) as a pale-orange colored liquid. MS(FAB,Pos.):m/z=122[M+H]+1H-NMR(500MHz,CDCl3):delta=2.67(3H,s),7.40(1H,dd,J=7.8,4.6Hz),7.64(1 H,d,J=7.8Hz),8.67(1H,d,J=4.6Hz),10.2(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,63071-09-0, its application will become more common.

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

Application of 52605-98-8, 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. 52605-98-8, name is 5-Bromo-2,3-dimethoxypyridine, molecular formula is C7H8BrNO2, 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.

As shown in step 2-v of Scheme 2, compound 1005 was suspended in 200 mL of dry THF along with PdCl2(Ph3P)2 (1.56 g, 2.23 mmol) and Ph3P (300 mg, 1.114 mmol). The mixture was flushed with N2 for 10 minutes. Triethylamine (14.0 mL, 10.14 g, 0.1 mol) and trimethylsilylacetylene (11.3 mL, 7.84 g, 0.080 mmol) were added under a nitrogen atmosphere and stirring continued for 15 minutes more before the addition of Cu(I) iodide (500 mg; 2.65 mmol). The reaction mixture was stirred at ambient temperature for 4 hours, and then heated for 5 hours at 40 C. under N2. The mixture was suction filtered through a pad of diatomaceous earth, which was washed with additional THF. The volatiles were removed under reduced pressure. The residue was dissolved in DCM, washed with water (2*), brine, and dried over Na2SO4. After filtration, the volatiles were removed under reduced pressure and the residue purified by silica gel chromatography (DCM) to provide 2,3-dimethoxy-5-((trimethylsilyl)ethynyl)pyridine (5.7 g) as a beige solid: ESMS (M+1)=236; 1H NMR (CDCl3) delta 7.89 (d, J=1.88 Hz, 1H), 7.1 (d, J=1.88 Hz, 1H), 4.02 (s, 3H), 3.89 (s, 3H), 0.12 (s, 9H).

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 52605-98-8, 5-Bromo-2,3-dimethoxypyridine.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; US2011/81316; (2011); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 626-64-2, 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 626-64-2 as follows.

To a solution of the commercially available 4-pyridinol, 17, (500 mg, 5.26mmol) in anhydrous toluene (15 mL) was added tert-butyl 3-hydroxyazetidine-1-carboxylate, R-24, (910 mg, 5.26 mmol), Ph3P (1.67 g, 6.2 mmol) and DIAD(1 .27 g, 6.3 mmol), the sealed vial was irradiated in the microwave on aBiotage Smith Synthesis at 15000 for 3 h. The resulting mixture was cooledto room temperature and concentrated under vacuo. The mixture was quenched into water, extracted with DOM, dried with anhydrous Na2504, concentrated to give the crude product which was purified by prep-TLO to give KR-30 (60 mg, 57.1%) as a pale yellow solid. ESI-MS (Mi-i): 251.1 calc.for 013H18N203: 250.1.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,626-64-2, its application will become more common.

Reference:
Patent; FUNDACION PARA LA INVESTIGACION MEDICA APLICADA; CUADRADO TEJEDOR, Maria Del Mar; FRANCO FERNANDEZ, Rafael; GARCIA OSTA, Ana Maria; OYARZABAL SANTAMARINA, Julen; RABAL GRACIA, Maria Obdulia; WO2014/131855; (2014); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 72990-37-5 , The common heterocyclic compound, 72990-37-5, name is 3-Chloroisonicotinaldehyde, molecular formula is C6H4ClNO, 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-chloropyridine-4-carbaldehyde (3.58 g, 25.3 mmol) in MeOH(150 mL) at 0 C was added NaBH4 (1.91 g, 50.6 mmol) portion wise. The mixture was stirred at this temperature for 5 min then allowed to warm up to rt and stirred at this temperature for 1.5 h. The reaction mixture was quenched with saturated aqueous solution of NH4Cl. Volatiles were removed in vacuo and the aqueous layer was extracted with EtOAc (150 mL). The organic layer was washed successively with water (150 mL) and brine (150 mL), dried over Na2SO4, filtered and concentrated in vacuo to give chloropyridine 33 (3.58 g, 99%) as a white solid which was used in the next step without further purification.

The synthetic route of 72990-37-5 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Jepsen, Tue Heesgaard; Glibstrup, Emil; Crestey, Francois; Jensen, Anders A.; Kristensen, Jesper Langgaard; Beilstein Journal of Organic Chemistry; vol. 13; (2017); p. 988 – 994;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 1093880-37-5, Adding some certain compound to certain chemical reactions, such as: 1093880-37-5, name is 6-Chloro-2-fluoronicotinaldehyde,molecular formula is C6H3ClFNO, 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 1093880-37-5.

Example 112A methyl 3 -(3 -(6-chloro-2-fluoropyridin-3 -yl)-3 -hydroxypropanoyl)benzoate A solution of methyl 3-acetylbenzoate (1 g, 5.61 mmol) in tetrahydrofuran (25 mL) was cooled to – 78 C, treated dropwise with 1 M lithium bis(trimethylsilyl)amide in tetrahydrofuran (7.30 ml, 7.30 mmol), stirred at – 78 C for 15 minutes, treated dropwise with a solution of 6- chloro-2-fluoronicotinaldehyde (0.895 g, 5.61 mmol) in tetrahydrofuran (10 mL), stirred at -78 C for 15 minutes, treated with saturated NH4C1 solution (30 mL) and the mixture was allowed to warm to near room temperature. The mixture was extracted with ethyl acetate (30 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (20 mL). The combined organic layers were washed with brine, dried (MgS04), filtered, and concentrated. The residue was chromatographed on silica gel and eluted with a gradient of 20 % – 100 % ethyl acetate in heptanes to provide the title compound (1.35 g, 4.00 mmol, 71.2 % yield). 1H NMR (400 MHz, CDCl3) 5 ppm 8.56 (t, J = 1.8 Hz, 1H), 8.28 (dt, J= 7.7, 1.5 Hz, 1H), 8.15 (dt, J = 7.9, 1.6 Hz, 1H), 8.10 – 8.05 (m, 1H), 7.59 (t, J = 7.8 Hz, 1H), 7.30 (dd, J= 7.8, 1.0 Hz, 1H), 5.53 (dt, J= 9.4, 2.9 Hz, 1H), 3.96 (s, 3H), 3.89 (d, J= 3.9 Hz, 1H), 3.55 (dd, J= 18.0, 2.4 Hz, 1H), 3.29 (dd, J= 18.0, 9.3 Hz, 1H); MS (ESI) m/z 338 (M+H)+.

According to the analysis of related databases, 1093880-37-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ABBVIE INC.; KYM, Philip, R.; WANG, Xueqing; SEARLE, Xenia, B.; LIU, Bo; YEUNG, Ming, C.; ALTENBACH, Robert, J.; VOIGHT, Eric; BOGDAN, Andrew; KOENIG, John, R.; (332 pag.)WO2016/69757; (2016); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 55314-16-4, 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.55314-16-4, name is 1-(3-Pyridyl)-3-(dimethylamino)-2-propen-1-one, molecular formula is C10H12N2O, molecular weight is 176.2151, as common compound, the synthetic route is as follows.

The starting material was added 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one (Compound 4) (1.76 g, 0.01 mol) in a three-neck flask.Guanidine hydrochloride (2.87 g, 0.03 mol)And sodium hydroxide (1.2g, 0.03mol), add 25ml of solvent t-butanol, stir, heated in a constant temperature oil bath to 85 C reflux reaction, 6-8h. After the reaction is completed, the solvent is spin-dried, an appropriate amount of water and ethyl acetate are added, the insoluble solid is filtered, and the filter cake is washed with water and dried to obtain a yellow solid; the filtrate is further subjected to extraction, the organic phase is collected, dried, and the solvent is dried and dried. The solid was subjected to column chromatography to give a pale yellow solid, Compound 5 (1.55 g, yield: 90%).

Statistics shows that 55314-16-4 is playing an increasingly important role. we look forward to future research findings about 1-(3-Pyridyl)-3-(dimethylamino)-2-propen-1-one.

Reference:
Patent; Southeast University; Cai Jin; Ning Yao; Ji Min; Wang Yingying; Huang Mingqi; (20 pag.)CN110078708; (2019); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 199522-66-2, 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. 199522-66-2, name is N1-(5-Bromopyrid-2-yl)ethane-1,2-diamine, molecular formula is C7H10BrN3, 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.

Step 2: 3-[2-(5-Bromo-pyridin-2-ylamino)-ethyl]-3H-quinazolin-4-one (compound 75) A suspension of primary amine 73 (1.17 g, 5.40 mmol) and isatoic anhydride 74 (880 mg, 5.40 mmol) in methanol (25 mL) was stirred for 3 h at 50 C. and then concentrated. The resulting oily residue was dissolved in 88% formic acid (20 mL) and refluxed overnight. After removal of formic acid, the solid residue was purified through column chromatography on silica gel (5% methanol in dichloromethane) to give 1.24 g (3.6 mmol, 67% yield) of 75. 13C NMR (300 MHz, CDCl3): 161.6, 156.8, 147.7, 147.6, 147.2, 139.8, 134.5, 127.4, 126.8, 126.3, 121.6, 110.1, 107.0, 46.3, 40.1. LRMS=347.1 (M+1).

According to the analysis of related databases, 199522-66-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MethylGene, Inc.; US2005/288282; (2005); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem