Category: pyridine-derivatives

Electric Literature of 76469-41-5, 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. 76469-41-5, name is 2,3,5-Trifluoropyridine, molecular formula is C5H2F3N, 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.

EXAMPLE 1(R)-(trans-(1-carbamoyl-4-adamantyl)) 3-(3,5-difluoropyridin-2-yloxy)pyrrolidine-1- carboxylateStep 1; To a stirred solution of (R)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate(1.1O g, 5.89 mmol) and 2,3,5-trifluoropyridine (0.86 g, 6.48 mmol) in dry THF (20 ml.) and dry DMF (4 ml_), at rt was added 60% NaH in oil (0.35 g, 8.84 mmol). The mixture was stirred in a 40 0C oil bath overnight, cooled to rt, diluted with ether (175 ml_), washed with water (25 mL) and brine (25 ml_), and dried over Na2SO4.Removal of the solvent left a dark oil (1.94 g) which was purified by chromatography on a 40-g silica cartridge eluted with a 0 – 100% EtOAc in hexanes gradient to afford (R)-tert-butyl 3-(3,5-difluoropyridin-2-yloxy)pyrrolidine-1- carboxylate (0.83 g, 47%). LC-MS Method 1 tR = 1.85 min, m/z = 301.

According to the analysis of related databases, 76469-41-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; VITAE PHARMACEUTICALS, INC.; CLAREMON, David, A.; LEFTHERIS, Katerina; SINGH, Suresh, B.; TICE, Colin, M.; YE, Yuanjie; ZHUANG, Linghang; WO2010/141424; (2010); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 1003-73-2, 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. 1003-73-2, name is 3-Methylpyridine 1-oxide, molecular formula is C6H7NO, 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.

Into the flask, 300 g of methylene chloride and 50 g of 3-picoline-N-oxide were added and the mixture was stirred and cooled to 5°C at a constant pressure.A dropping funnel was charged with a mixed solution of 240 g of 2,4,6-triisopropyl-3-benzoyl chloride and 200 g of methylene chloride and slowly added dropwise to the dichloromethane mixture of 3-picoline-N-oxide. In the dropping process, the reaction temperature is controlled at 5 to 10°C.The addition was completed within about 3 hours. The reaction was incubated for 2 hours and then warmed to 40°C overnight.After the end of the reaction, cool down to 5 ~ 10 °C, slowly add 200g of water, after desolvation steam distillation, collecting 100 ~At 102°C/760mmHg, the distillate was extracted with methylene chloride. After the aqueous layer was separated, 57.4 g of product was de-solvated.The content of 2-chloro-5-methylpyridine was 98percent, 2-chloro-3-methylpyridine was 0.5percent, and the yield of 2-chloro-5-methylpyridine was 96.2percent.

According to the analysis of related databases, 1003-73-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Nanjing Hong Sun Biochemical Co., Ltd.; Chen Honglong; Mu Dengyou; Xue Yi; Chen Xinchun; Zhong Jingsong; Wang Fujun; Yang Cheng; (5 pag.)CN107721912; (2018); A;,
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. 39919-65-8, name is 2,5-Dibromo-6-methylpyridine, molecular formula is C6H5Br2N, 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. name: 2,5-Dibromo-6-methylpyridine

Add to the reaction flask3,6-dibromo-2-methylpyridine (1.0 g, 3.9 mmol)And anhydrous ether (10 mL) were cooled to -78C,N-BuLi (1.6 M in hexanes, 2.4 mL, 3.9 mmol) was added dropwise,After stirring for 1 hour, anhydrous DMF (307 mg, 4.2 mmol) was added,The reaction was stirred at room temperature for 1 hour. Saturated ammonium chloride solution (10 mL) was added,Ethyl acetate (20 mL x 3). Combine organic phase,Saturated sodium chloride solution (20mL), dried over anhydrous sodium sulfate, suction filtration,Concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate / petroleum ether = 1: 10)The resulting residue was purified to give the title compound (0.4 g, white solid) in 51% yield.

With the rapid development of chemical substances, we look forward to future research findings about 39919-65-8.

Reference:
Patent; Gan & Lee Pharmaceuticals; Liu, Wenjian; Yin, Lei; Li, Heng; (94 pag.)CN106608879; (2017); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 53937-02-3, Adding some certain compound to certain chemical reactions, such as: 53937-02-3, name is 4-Benzyloxy-2-(1H)-pyridone,molecular formula is C12H11NO2, 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 53937-02-3.

b) 4-(Benzyloxy)-1-(1,2,3,4,5,6-hexahydroazepino[4,5-b]indol-8-yl)pyridin-2(1H)-one hydrochloride A suspension of 4-(benzyloxy)pyridin-2(1H)-one (71 mg, 0.35 mmol), tert-butyl 8-bromo-6-tosyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (202 mg, 0.389 mmol), CuI (81 mg, 0.43 mmol), 8-hydroxyquinoline (62 mg, 0.43 mmol) and Cs2CO3 (127 mg, 0.389 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under N2 and stirred at 135 C. for 4.5 h. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added, and the resulting suspension was stirred at 25 C. for 30 min. The suspension was passed through a plug of silica gel, and the filtrate was washed with brine. The resulting solution was dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography (silica gel, (1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) afforded 190 mg of a yellow solid. NaOH (594 mg, 14.8 mmol) was added to a solution of the yellow solid in 1:1 MeOH/CH2Cl2 (20 mL) under N2, and the resulting suspension was stirred at reflux for 16 h. The reaction was cooled, H2O was added, and the resulting suspension was filtered. Flash chromatography (silica gel, (1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) afforded a green solid. Preparative HPLC (Phenomenex Luna C18 (2), 250.0*50.0 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA) afforded 50 mg of a white powder. 2 N HCl in Et2O (200 mL) was added to a solution of the white powder in 1:1 CH2Cl2/MeOH (4 mL) under N2, and the resulting suspension was stirred at 25 C. for 18 h. The suspension was filtered, and the solid was washed with Et2O to afford the title compound (35 mg, 23%) as a white solid: mp 258-260 C.; 1H NMR (500 MHz, DMSO-d6) delta 11.18 (s, 1H), 9.06 (br s, 2H), 7.57-7.35 (m, 7H), 7.25 (s, 1H), 6.90 (d, J=8.0 Hz), 6.11-6.07 (m, 1H), 5.96 (s, 1H), 5.15 (s, 2H), 3.45-3.30 (m, 4H), 3.20-3.15 (m, 2H), 3.12-3.06 (m, 2H); ESI MS m/z 386 [M+H]+.

According to the analysis of related databases, 53937-02-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ALBANY MOLECULAR RESEARCH, INC.; US2011/3793; (2011); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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.153034-86-7, name is 2-Chloro-4-iodopyridine, molecular formula is C5H3ClIN, molecular weight is 239.44, as common compound, the synthetic route is as follows.Application In Synthesis of 2-Chloro-4-iodopyridine

Intermediate 1; 4-Iodo-1H-pyridin-2-one; To 10.0 g (41.8 mmol) 2-chloro-4-iodopyridine in 100 mL AcOH are added 17.1 g (208 mmol) NaOAc and the reaction mixture is heated at 180 C. for 2 h in a microwave oven. DCM and water are added to the reaction mixture and the layers are separated. The organic layer is washed with water, dried with Na2SO4 and the solvent is removed in vacuo. The crude product is triturated with TBME.C5H4INO (M=221.0 g/mol),ESI-MS: 222 [M+H]+ Rf (TLC): 0.3 (silica gel DCM/MeOH 9/1)

At the same time, in my other blogs, there are other synthetic methods of this type of compound,153034-86-7, 2-Chloro-4-iodopyridine, and friends who are interested can also refer to it.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; US2012/214785; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 110860-92-9, 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. 110860-92-9, name is 5,6-Dichloropyridin-3-ol. A new synthetic method of this compound is introduced below.

Sodium acetate (4.Og, 49.38mmoI) was added to a mixture of 5,6-dichloropyridin-3-ol (8g, 49.38mmol), Pd(OAc)2 (1.43g, 6.41 mmol) and Pd(dppf)C12 DCM complex (5.23g, 6.4lmmol) in EtOH (lOOmL) in an autoclave. The autoclave was filled with CO gas (22Opsi) and stirred at 90C for 6 h. The reaction mass was cooled to RT, excess gas evacuated in vacuo and the reaction mass was filtered through a celite bed. It was washed with EtOAc and the clear filtrate was concentrated under reduced pressure. Theresidue was purified by CC (0-40% EtOAc in PE) and the pure fractions were concentrated to get ethyl 3- chloro-5-hydroxypicolinate (9.2g, 93%) as a white solid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,110860-92-9, 5,6-Dichloropyridin-3-ol, and friends who are interested can also refer to it.

Reference:
Patent; GRUeNENTHAL GMBH; SCHUNK, Stefan; REICH, Melanie; JAKOB, Florian; DAMANN, Nils; HAURAND, Michael; KLESS, Achim; ROGERS, Marc; SUTTON, Kathy; WO2015/158427; (2015); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 78607-36-0 ,Some common heterocyclic compound, 78607-36-0, molecular formula is C5H3ClIN, 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.

EXAMPLE 31K 3-(4-tert-butylphenyl)-1-({2-[(2-chloropyridin-3-yl)amino]pyridin-4-yl}methyl)-5,5-dimethylimidazolidine-2,4-dione To a solution of 0.8 g of 1-[(2-aminopyridin-4-yl)methyl]-3-(4-tert-butylphenyl)-5,5-dimethylimidazolidine-2,4-dione hydrochloride obtained in stage c) of Example 7 in 50 mL of dioxane are successively added under argon 0.628 g of 2-chloro-3-iodopyridine, 2.8 g of caesium carbonate, 150 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) (xantphos) and 49 mg of palladium diacetate. The reaction mixture is heated at 90 C. for 3 hours and then filtered, and the filtrate is concentrated under reduced pressure. The residue is purified by chromatography on a column of silica, eluding with a mixture of cyclohexane and ethyl acetate (70/30 by volume) to give 0.51 g of 3-(4-tert-butylphenyl)-1-({2-[(2-chloropyridin-3-yl)amino]pyridin-4-yl}methyl)-5,5-dimethylimidazolidine-2,4-dione, the characteristics of which are as follows: 1H NMR spectrum at 400 MHz: 1.31 (s, 9H); 1.43 (s, 6H); 4.57 (s, 2H); 6.89 (dd, J=1.5 and 5.5 Hz, 1H); 7.11 (broad s, 1H); 7.39 (m, 3H); 7.52 (d, J=8.5 Hz, 2H); 8.00 (dd, J=2.0 and 5.0 Hz, 1H); 8.10 (d, J=5.5 Hz, 1H); 8.55 (m, 2H). Mass Spectrum (ES): m/z=478 [M+H]+; m/z=476 [M-H]-

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. 78607-36-0, 2-Chloro-3-iodopyridine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; AVENTIS PHARMA S.A.; US2009/82379; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 1289093-31-7, 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 1289093-31-7 as follows.

Preparation 14: methyl 1 -i5-chloro-6-isobutoxypyridin-3-yl)-3-cvclopropyl-1 H- indazole-5-carboxylate; A mixture of methyl 3-cyclopropyl-1 H-indazole-5-carboxylate [preparation 9] (100mg, 0.396mmol), Cul (7.6mg, 0.40mmol), K3P04 (168mg, 0.792mmol), and 5-bromo-3- chloro-2-isobutoxy-pyridine [preparation 30] (105mg, 0.396mmol) was added to a septum sealed reaction vial and degassed. A solution of trans-N, N’- dimethylcyclohexane-1 ,2-diamine in toluene (2ml) was added. The mixture was degassed and filled with nitrogen three times, then stirred at 1 10C for 4 days. The mixture was allowed to cool and then partitioned between water (5ml) and DCM (5ml). The DCM phase was separated and the aqueous extracted with further DCM (5ml). The extracts were combined and evaporated onto silica. Purification by column chromatography (ISCO Companion, silica 12g, eluted with a gradient of heptane to 40% EtOAc in heptane) gave the title compound as clear oil (100.4mg).1 H NMR (400 MHz, CDCI3) delta ppm 1 .07 (d, 6H), 1 .19-1 .12 (m, 4H), 2.18 (septuplet, 1 H), 2.27-2.34 (m, 1 H), 3.97 (s, 3H), 4.21 (d, 2H), 7.55 (dd, 1 H), 7.98 (d, 1 H), 8.09 (dd, 1 H), 8.35 (d, 1 H), 8.58 (dd, 1 H).LCMS (Method A5) Rt 1 .83 min, MS m/z 400 [MH]+

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1289093-31-7, its application will become more common.

Reference:
Patent; PFIZER LIMITED; BELL, Andrew Simon; DE GROOT, Marcel John; LEWTHWAITE, Russell Andrew; MARSH, Ian Roger; SCIAMMETTA, Nunzio; STORER, Robert Ian; SWAIN, Nigel Alan; WO2012/95781; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 139022-27-8, 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 139022-27-8 as follows.

Example 166-fluoro-3-iodo-imidazo^ ,2-alpha]pydine (29)As shown in Fig. 5, 6-Fluoro-3-iodo-imidazo[1 ,2-alpha]pyridine (29) was prepared according to a literature procedure (Enguehard et al., J. Org. Chem. 65: 6572-6575 (2000), incorporated herein by reference in its entirety). N-iodosuccinimide (9.2g, 40.8 mmol) was added to a solution of 6-fluoro-imidazo[1 ,2-alpha]pyridine 26 (Example 15) (7.6g, 40.8 mmol) in dry acetonitrile (100 ml.) at O0C. The reaction was warmed to room temperature and then stirred for 12 hours. The mixture was filtered and the cake washed with acetonitrile and water and dried under high vacuum to afford 6-fluoro-3-iodo-imidazo[1 ,2-alpha]pyridine 29 off white solid. 8.5 g, 88% yield.1H NMR (300 MHz, CDCI3, 297K) delta 7.14 (td, J = 2.1 , 7.8 Hz, 1 H), 7.59 (dd, J = 5.1 , 9.9 Hz, 1 H), 7.72 (s, 1 H), 8.07 (distorted t, J = 3.0 Hz, 1 H).ESI MS (MeOH) calcd for C7H4FIN2 262.03, found m/z (M++1 ) 263.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,139022-27-8, its application will become more common.

Reference:
Patent; ISIS INNOVATION LTD.; EBETINO, Frank, Hallock; MAZUR, Adam; LUNDY, Mark, Walden; RUSSELL, Robert, Graham Goodwin; WO2010/33978; (2010); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 272-52-6 ,Some common heterocyclic compound, 272-52-6, molecular formula is C6H5N3, 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.

Into a vessel was placed a solution comprising 1.0 g of lH-pyrazolo[4,3- b]pyridine (Exp-l-gl, 8.4 mmol) in 12 mL of MeOH/H20 (1 : 1, vol). Into the solution was added dropwise a solution of Br2 ( 1.6 g, 10 mmol) in MeOH/H20 (1 : 1, 5 mL) maintaining the solution temperature at 0 C during the addition. The reaction mixture thus prepared was stirred at this temperature for 40 min. The resulting precipitate was collected by filtration and the filter cake thus obtained was neutralized with saturated Na2C03 solution. The neutralized precipitate was filtered, washed with water and dried in vacuum. The crude product thus obtained (Exp-l-g2,1.2 g, 71 %) was used for the next step directly without purification. The identity of the product was verified by proton NMR in accordance with the procedures set forth above. 1HNMR: (400 MHz, DMSO) delta 13.66 (br, 1H), 8.55 (d, 1H, J = 4.0 Hz), 8.03 (dd, 1H, J = 8.8 Hz, 1.2 Hz), 7.42-7.45 (m, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,272-52-6, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIVERTON, Nigel; JONES, Philip; LEI, Zhiyu; LIU, Fuqing; LUO, Yunfu; DONG, Jingchao; SOLL, Richard; WO2013/63100; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem