Pyridine-derivatives

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. 71902-33-5, name is 3,5-Difluoropyridine, molecular formula is C5H3F2N, 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. Formula: C5H3F2N

Intermediate 30 l-(3,5-Difluoropyridin-2-yl)-2-methoxyethanone3,5-Difluoropyridine (5.0 g, 43.45 mmol) in THF was cooled to -720C (external -8O0C). LDA (23.9 mL, 1.1 eq.) was added drop-wise at such rate that the internal temp did not increase more than 30C during addition. The reaction mixture turned into a deep brownish, thick phase and was stirred for 30 minutes at this temperature. TMS-Cl (43.4 mL, 43.45 mmol) was added via syringe in a relatively fast fashion. The reaction became a clear and light yellow solution. LDA (23.9 mL, 1.1 eq.) was added drop-wise in a quicker version, and the reaction mixture was allowed to stir for 2 hours. Methyl 2-methoxyacetate (5.59 mL, 56.48 mmol) was added quickly through a syringe. The reaction mixture was quenched at -780C by adding 20 ml of saturated NH4Cl solution. Evaporation of the organic extracts under reduced pressure gave a colored residue. Purification utilizing ISCO (0-^25percent EtOAc/hexanes), gave the title product (3 g). LCMS: 188 [M+H]+.

With the rapid development of chemical substances, we look forward to future research findings about 71902-33-5.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; CHUAQUI, Claudio, Edmundo; HUANG, Shan; IOANNIDIS, Stephanos; SHI, Jie; SU, Mei; SU, Qibin; WO2010/38060; (2010); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 106447-97-6 ,Some common heterocyclic compound, 106447-97-6, molecular formula is C6H5F3N2, 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.

Method 7; Synthesis of 5-bromo-4-(trifluoromethvl)-2-pvridylamine; [0247] To a solution of 2-amino-4-trifluoromethylpyridine (10.0 g, 62.1 mmol) in chloroform (200 mL) was added NBS (12.0 g, 67.4 mmol). The solution was stirred in the dark for 2 hours, at which time it was added to DCM (200 mL) and IN NaOH (200 mL). Upon mixing, the layers were separated and the organic layer was washed with NaCl(sat) (10O mL), dried over Na2SO4, filtered and concentrated. The crude material was purified by Silica gel chromatography (0-5% EtOAc/ CH2Cl2) yielding 12.O g (80%) of 5-bromo-4-(trifluoromethyl)-2-pyridylamine: LCMS (m/z): 241/243 (MH+); 1H NMR (CDCl3): delta 8.28(s, IH), 6.77(s, IH), 4.78(bs, 2H).

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. 106447-97-6, 2-Amino-4-(trifluoromethyl)pyridine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NOVARTIS VACCINES AND DIAGNOSTICS, INC.; WO2008/98058; (2008); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 7295-76-3, 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 7295-76-3, name is 3-Methoxypyridine. This compound has unique chemical properties. The synthetic route is as follows.

(a) To a solution of t-BuLi (216 ml, 1.7M, 0.367 mol) in 1 L of THF at -78 C was added dropwise 1-bromo-2,4,6-trimethyl-benzene (35.6 g, 0.178 mol) over a period of 45 minutes. The mixture was stirred at -78 C. for 1 hour, 3-methoxypyridine (15 g, 0.138 mol) was added and then the mixture was stirred at -23 C. for 3 hours. The above reaction mixture was cooled to -78 C. and 13 g (0.2 mol) of DMF in 25 ml of THF was added and the mixture was stirred for 1 hour. The reaction mixture was quenched with 250 ml of brine, the mixture was stirred overnight, and diluted with 1 L of ether. The aqueous layer was extracted with ethyl acetate (1 L), the combined organic layer was dried over potassium carbonate, and concentrated in vacuo to afford 7.5 g of 3-methoxypyridyl-2-carboxaldehyde.

According to the analysis of related databases, 7295-76-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Sterling Winthrop Inc.; US5554620; (1996); A;,
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.20265-38-7, name is 2-Methoxypyridin-3-amine, molecular formula is C6H8N2O, molecular weight is 124.14, as common compound, the synthetic route is as follows.Quality Control of 2-Methoxypyridin-3-amine

Step 1-Synthesis of 6-chloro-N-(2-methoxypyridin-3-yl)pyrimidin-4-amineTo a solution of 4,6-dichloropyrimidine (660.04 mg, 4.43 mmol) in 1-butanol (10 mL) was added DIPEA (0.67 ml, 4.03 mmol) followed by 2-methoxypyridin-3-amine (500 mg, 4.03 mmol).The reaction mixture was then heated to 90° C. for 2 hr.The reaction mixture was then concentrated in vacuo and partitioned between DCM and water.A precipitate was removed by filtration and the organics extracted (2*20 ml DCM).The combined organic extracts were then washed with 0.5M HCl (5 ml) and then dried (Na2SO4), filtered and concentrated in vacuo to give the title intermediate (300 mg, LC-MS purity=83percent); LC-MS: m/z=+236.95/238.90 (M+H)+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,20265-38-7, 2-Methoxypyridin-3-amine, and friends who are interested can also refer to it.

Reference:
Patent; Genentech, Inc.; US2012/214762; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 193902-78-2, Adding some certain compound to certain chemical reactions, such as: 193902-78-2, name is tert-Butyl 4-(5-nitropyridin-2-yl)piperazine-1-carboxylate,molecular formula is C14H20N4O4, 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 193902-78-2.

309. Step 2: /V-(5-nitropyridin-2-yl)piperazine (B-3)To compound B-2 (19.45 g, 0.0631 mol) dissolved in CH2CI2 (250 ml_) and cooled to 0 0C was added trifluoroacetic acid (50 ml_). The resulting reaction mixture was stirred at RT for 16 h then concentrated. The crude product was dissolved in CH2CI2 (250 ml_) and made basic with the addition of 1 N aqueous NaOH (200 ml_) and 3 N aqueous NaOH (100 ml_). The layers were separated, and the aqueous solution extracted with CH2CI2. The combined organic extract was dried (MgSO4), filtered, and concentrated to give the product N-(2-fluorophenyl)-4-(5-nitropyridin-2-yl)piperazine-1-carboxamide (B- 3) as a yellow solid (13.13 g, 100% yield). MS (M+1): 209

According to the analysis of related databases, 193902-78-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SCHERING CORPORATION; TING, Pauline, C.; ASLANIAN, Robert, G.; CAPLEN, Mary Ann; CAO, Jianhua; KIM, David, Won-Shik; KIM, Hyunjin; KUANG, Rongze; LEE, Joe, F.; SCHWERDT, John, H.; WU, Heping; ZHOU, Gang; ZORN, Nicolas; WO2010/59606; (2010); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 16498-81-0, 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. 16498-81-0, name is 2-Methoxynicotinic acid, molecular formula is C7H7NO3, 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.

2-Methoxy-3-pyridinecarboxylic acid (0.028 mol) was dissolved in DCM (150 ml). Thionyl chloride (8.2 ml; 0.112 mol)) was added dropwise to this mixture and the mixture was refluxed for 2 hours and 30 minutes. The solvent was evaporated. Then DCM (150 ml) was added and the solvent was evaporated again. The crude compound was dissolved in DCM (150 ml). First l-(phenylmethyl)-3-pyrrolidinamine (0.028 mol) was added and then a saturated aqueous NaHCCb solution (75 ml) was added. The mixture was reacted for 2 hours. Then, the layers were separated. The separated organic layer was dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography (eluent: from 100 % CH2Cl2 till CH3OH/CH2C12 1/100). The product fractions were collected and the solvent was evaporated, yielding 7.97 g of intermediate (23); 2-Methoxy-3-pyridinecarboxylic acid (0.028 mol) was dissolved in DCM (150 ml). Thionyl cloride (8 ml; 0.112 mol) was added dropwise to this mixture and the mixture was refluxed for 2 hours and 30 minutes. The solvent was evaporated. Then DCM (150 ml) was added and the solvent was evaporated again. The crude compound was dissolved in DCM (150 ml). First N-methyl-N-(phenylmethyl)-l,3-propanediamine (0.028 mol) was added and then a saturated aqueous nuaHCtheta3 solution (75 ml) was added. The mixture was reacted for 2 hours. Then, the layers were separated. The separated organic layer was dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography (eluent: from 100 % CH2Cl2 till CH3OH/CH2C12 1/100). The product fractions were collected and the solvent was evaporated, yielding 8.7 Ig of intermediate (27); -Methoxy-3-pyridinecarboxylic acid (0.00485 mol) was dissolved in DCM (50 ml). Thionyl chloride (1.4 ml) was added dropwise to this mixture and the mixture was refluxed for 2 hours and 30 minutes. The solvent was evaporated. Then DCM (50 ml) was added and the solvent was evaporated again. The crude compound was dissolved in DCM (50 ml). First 4-(phenylmethyl)-2-morpholinemethanamine (0.00485 mol) was added and then a saturated aqueous NaHCO3 solution (25 ml) was added. The mixture was reacted for 2 hours. Then, the layers were separated. The separated organic layer was dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography (eluent : from 100 % CH2Cl2 till CH3OH/CH2C12 1/100). The product fractions were collected and the solvent was evaporated, yielding 1.6 g of intermediate (29); 2-Methoxy-3-pyridinecarboxylic acid (0.0269 mol) was dissolved in DCM (150 ml). Thionyl chloride (8 ml) was added dropwise to this mixture and the mixture was refluxed for 2 hours and 30 minutes. The solvent was evaporated. Then DCM (150 ml) was added and the solvent was evaporated again. The crude compound was dissolved in DCM (150 ml). First 4-aminohexahydro-lH-azepine-l-carboxylic acid, ethyl ester (0.0269 mol) was added and then a saturated aqueous NaetaCtheta3 solution (75 ml) was added. The mixture was reacted for 2 hours. Then, the layers were separated. The separated organic layer was dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography (eluent: from 100 % CH2CL) till CH3OH/CH2Cl2 1/100). The product fractions were collected and the solvent was evaporated, yielding 8.63 of intermediate (31).

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 16498-81-0, 2-Methoxynicotinic acid.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; WO2008/49808; (2008); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 18437-58-6, 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 18437-58-6, name is 4-Amino-2-picoline. This compound has unique chemical properties. The synthetic route is as follows.

To a solution of Intermediate 83B (10 mg, 0.016 mmol) in THF (1 mL) was added2-methylpyridin-4-amine (5.35 mg, 0.049 mmol) and DIEA (0.029 mL, 0.165 mmol) inDCM (1 mL). The mixture was stirred at room temperature for 2 h. TBAF (0.165 mL, 0.165 mmol) was added and the mixture was stirred at room temperature overnight. The reaction was quenched by addition of a small amount of MeOH/water/0. 1% TFA (HPLC solvent). Solvent was removed under vacuum. The residual was dissolved in DMSO andpurified via preparative LC/MS (method D, 30-70% B over 20 mm., then a 5-mm hold at100% B). Fractions containing the desired product were combined and dried via centrifugal evaporation to give Example 85 (0.8 mg, 1.420 imol, 8.60 % yield). ?H NMR (500MHz, DMSO-d6) 8.81 (s, 1H), 8.75 (d, J=1.7 Hz, 1H), 8.35 (d, J5.8 Hz, 1H), 7.95 (s, 1H), 7.50-7.39 (m, 2H), 7.15 (d, J=11.0 Hz, 1H), 5.65 (br. s., 1H), 4.83 (d, J3.6 Hz,2H), 4.71 (br. s., 1H), 4.64 (dd, J=1 1.6, 2.2 Hz, 1H), 4.57-4.44 (m, 2H), 4.31 (dd, J1 1.6,7.2 Hz, 1H), 4.10 (s, 3H), 2.46 (s, 3H). LC-MS: method C, RT = 1.48 mm, MS (ESI) m/z: 564.10 (M+H). Analytical HPLC purity (method B): 100%.

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 18437-58-6, 4-Amino-2-picoline.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; ZHANG, Xiaojun; PRIESTLEY, Eldon Scott; HALPERN, Oz Scott; JIANG, Wen; REZNIK, Samuel Kaye; RICHTER, Jeremy M.; (545 pag.)WO2018/13776; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 56622-54-9, 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.56622-54-9, name is (6-Methylpyridin-3-yl)methanamine, molecular formula is C7H10N2, molecular weight is 122.17, as common compound, the synthetic route is as follows.

2-Fluoro-N-((6-methylpyridin-3-yl)methyl)-9H-purin-6-amineTo a stirred solution of 6-chloro-2-fluoropurine ( 0.4g, 2.3 mmol) in n-BuOH (50 ml) under an argon atmosphere at O0C, was added DIEA (2.5 ml, 14.7 mmol) followed by (6-methylpyridin-3-yl)methanamine (0.36g, 2.95 mmol). The reaction mixture was stirred at this temperature for 1 h and then allowed to return to room temperature and stirred for 4h, it was still seen incomplete, hence heated the reaction to 1000C and left at that temperature for 8h. The solvent was evaporated in vacuo and the residue was purified by gradient column chromatography on silica gel, eluted with CHCl3 :MeOH (100:0 ? 90:10), to afford the product as a white solid; Yield: 0.38 g (65%) deltaH CDCl3, 250 MHz) 2.44 ( 3 H, s, CH3), 3.66 – 3.57 ( 2 H, m, NHCH2), 4.63 ( 1 H, s, br, NH),7.25 ( 1 H, d, J 7.5, ArH), 7.71 (1 H, dd, J 2.5, 7.5, ArH), 8.14 ( 1 H, s, ArH), 8.49 (1 H, s, ArH), 9.07 (1 H, s, br, NH); deltac ( CDCl3, 250 MHz) 159.12 (C), 158.62 (C), 157.61 (C), 155.56 (C), 147.44 (CH), 146.99 (CH), 136.32 (C), 123.05 (2 x CH), 119.42 (C), 41.64 (CH2), 18.47 (CH3); m/z 259.2 (M + H)

Statistics shows that 56622-54-9 is playing an increasingly important role. we look forward to future research findings about (6-Methylpyridin-3-yl)methanamine.

Reference:
Patent; CYCLACEL LIMITED; CANCER RESEARCH TECHNOLOGY LIMITED; WO2008/122767; (2008); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 1228014-35-4, Adding some certain compound to certain chemical reactions, such as: 1228014-35-4, name is tert-Butyl 4-bromo-1H-pyrrolo[2,3-b]pyridine-1-carboxylate,molecular formula is C12H13BrN2O2, 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 1228014-35-4.

j0704j A solution of tert-butyl 4-bromo-1H-pyrrolo[2,3-bjpyridine-1-carboxylate (XCII) (2 g, 6.8 mmol, 1.0 eq), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)-1,3,2-dioxaborolane (2.07 g, 8.16 mmol, 1.02 eq), KOAc (1.99 g, 20.4 mmol, 3 eq) in dioxane (25 mL) was degassed (x 3) with a water pump. Pd(dppf)C12 (246 mg, 0.34 mmol, 0.05 eq) was then added quickly in one portion under nitrogen. The reaction was stirred at 90C for 6 h. Water (100 mL) was added and extracted with EtOAc (x 3). Flash chromatography (PE: EtOAc 20:1) gave tert-butyl 4-(4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1H-pyrrolo[2,3 -bjpyridine- 1- carboxylate (C) as a green oil (2.0 g, 5.82 mmol, 86.4%). ?H NMR (CDC13, 400 MHz) ppm 1.39 (s, 12H), 1.67 (s, 9H), 6.93 (d, J4Hz, 1H), 7.54 (d, J4.8Hz, 1H), 7.65 (d, J4Hz, 1H), 8.51 (d, J4.4Hz, 1H); ESIMS found for C,8H25BN204 mlz 345.1 (M+H).

According to the analysis of related databases, 1228014-35-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SAMUMED, LLC; KC, Sunil Kumar; WALLACE, David Mark; CAO, Jianguo; CHIRUTA, Chandramouli; HOOD, John; (274 pag.)WO2017/24021; (2017); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 775288-71-6, 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. 775288-71-6, name is 1-(6-Nitropyridin-3-yl)piperazine, molecular formula is C9H12N4O2, 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.

A mixture of 5-Bromo-2-nitropyridine (203 g, 1.37 mol), piperazine (153 g, 1.77 mol), tetrabutylammonium iodide (25.2 g, 0.068 mol), and potassium carbonate (207 g, 1.50 mol) in dimethyl sulfoxide (2.6 L) was stirred at 80C overnight. The resultant reaction mixture was cooled to room temperature, and the mixture was poured into water (7 L). The resultant solid was collected by filtration, and the solid was washed with dichloromethane (1 L × 2) and dried. The filtrate was extracted with chloroform (2 L × 7). The resultant organic phase was washed with water (2 L) and then with saturated brine (2 L), and the organic phase was concentrated under reduced pressure to yield solid. The resultant solid products were combined together and used for the subsequent reaction without further purification. (0173) The solid product (490 g) was dissolved in THF (2 L) and water (500 mL), and sodium hydrogen carbonate (119 g, 1.42 mol) was added to the solution. To the resultant suspension was added di-tert-butyl dicarboxylate (262 g, 1.2 mol), and the mixture was stirred at room temperature for three hours. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with water (1 L) and extracted with dichloromethane (1 L × 3). The resultant organic phases were combined together and then washed with water (1 L). The aqueous phase was extracted with dichloromethane (300 mL). The resultant organic phases were combined together and dried over anhydrous magnesium sulfate. The solid was separated by filtration, and the filtrate was concentrated under reduced pressure. The resultant solid was suspended in ethyl acetate (2 L) and heated to 60C, and the solid was separated by filtration at 60C. The solid was dried under reduced pressure to yield the title compound (191 g, 62%) APCI-MS (M+H)+ 309.1, C14H20N4O4=308.15 1H-NMR delta(400 MHz, CDCl3) : 8.16 (d, J=9 Hz, 1H), 8.11 (d, J=3 Hz, 1H), 7.19 (dd, J=9.3 Hz, 1H), 3.64-3.61 (m, 4H), 3.45-3.42 (m, 4H), 1.47 (s, 9H)

According to the analysis of related databases, 775288-71-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Teijin Pharma Limited; MIZUNO, Tsuyoshi; SHIMADA, Tomohiro; UNOKI, Gen; EBISAWA, Masaru; TAKEUCHI, Susumu; MINAMIZONO, Kunio; SASAKI, Kosuke; YOKOSAKA, Takuya; IGARASHI, Junji; MARUYAMA, Akinobu; TAKAHASHI, Hiroshi; HORIE, Kyohei; SAKAI, Yuri; (447 pag.)EP3305785; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem