Category: 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. 1033772-26-7, name is Methyl 1H-pyrazolo[3,4-c]pyridine-5-carboxylate, molecular formula is C8H7N3O2, 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: C8H7N3O2

A solution of methyl 1-(4-fluorobenzyl)-3-formyl-1 H-pyrrolo[2,3-c]pyridine-5-carboxylate (312 mg, 1.0 mmol, 1.0 eq) in 4 mL anhydrous dichloromethane) was mixed with a solution of 3-methylpiperazin- 2-one (114 mg, 1.0 mmol, 1.0 eq) in 4 To a stirring solution of methyl 1 H-pyrazolo[3,4-c]pyridine-5-carboxylate (100 mg, 0.351 mmol) in methanol (4 mL) was added a 3.0 M solution of LiOH in water (0.351 mL, 1.05 mmol) and the mixture was stirred overnight, then 1.0 M hydrochloric acid in diethyl ether was added (1.05 mL, 1.05 mmol) and the solvent was evaporated under reduced pressure.. The crude solid was dissolved in DMF and N-methylhydroxylamine hydrochloride (58 mg, 0.698 mmol) was added followed by triethylamine (214 mL, 1.154 mmol) and HATU (266 mg, 0.698 mmol). The mixture was stirred overnight. Water was added and the mixture was extracted with dichloromethane (3 x 20 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The crude solid was dissolved in DMSO and purified by reverse phase preparative HPLC to provide a white solid (105 mg, 100% yield). ¹H NMR (DMSO-d6) : No. 10.24 (bs, 1 H), 9.26 (s, 1 H), 8.07 (s, 1 H), 7.37 (m, 2H), 7.15 (m, 2H), 5.81 (s, 2H), 3.31 (s, 3H). Anal. HPLC: >95% ( 254,222 nM). HRMS calcd for C15H13FN4O2 (M+H) 301.1088, found 301.1096.

With the rapid development of chemical substances, we look forward to future research findings about 1033772-26-7.

Reference:
Patent; PFIZER INC.; WO2005/103003; (2005); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 7169-95-1 ,Some common heterocyclic compound, 7169-95-1, molecular formula is C7H6BrN3, 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 5(S)-6-(2-hydroxy-2-methylpropyl)-6-isopropyl-3-((S)-l-(4-(2-methyl-[l,2,4]triazolo[l,5-a]pyridin-6-yl)phenyl)ethyl)-l,3-oxazinan-2-oneTo a solution of 6-bromo-2-methyl-[l,2,4]triazolo[l,5-a]pyridine (9.5 mg, 0.045 mmol) in DME (3 mL) was added Pd(PPh3)4 (5.2 mg, 0.0045 mmol) under N2. After being stirred at room temperature for 1 hour, the mixture was added a solution of (2^-6- (2-hydroxy-2-methylpropyl)-6-isopropyl-3-(f5>;l-(4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)phenyl)ethyl)-l,3-oxazinan-2-one (20 mg, 0.045 mmol) in ethanol (1.5 mL) and saturated NaHCO3 solution(l mL). The mixture was heated to reflux for 2 hours under N2. The reaction mixture was treated with ethyl acetate (10 mL) and water (10 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by preparative HPLC to give f5^-6-(2-hydroxy- 2-methylpropyl)-6-isopropyl-3-(5y)- 1 -(4-(2-methyl-[ 1 ,2,4]triazolo[ 1 ,5-a]pyridin-6-yl) phenyl)ethyl)-l,3-oxazinan-2-one (6.00 mg, 30%). LC-MS Method 2 tR = 0.99 min, m/z = 451. 1H NMR (CD3OD): 0.90 (d, 3H), 1.00 (d, 3H), 1.33 (d, 6H), 1.65 (d, 3H), 1.78 (d, IH), 1.93 (m, 2H), 2.17 (m, IH), 2.28 (m, IH), 2.58 (s, 3H), 2.84 (m, IH), 3.39 (m, IH), 5.73 (q, IH), 7.52 (d, 2H), 7.76 (m, 3H), 8.01 (d, IH), 8.99 (s, IH). (S)-6-(2-hydroxy-2-methylpropyl)-6-isopropyl-3-((S)-l-(4-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)phenyl)ethyl)-l,3-oxazinan-2-one was prepared as described in WO 2009/134400 Example 17.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,7169-95-1, its application will become more common.

Reference:
Patent; VITAE PHARMACEUTICALS, INC.; CLAREMON, David, A.; WO2010/91067; (2010); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 131747-55-2, 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 131747-55-2, name is 2-Fluoro-3-(hydroxymethyl)pyridine. This compound has unique chemical properties. The synthetic route is as follows.

Intermediate 13: 3-(bromomethyl)-2-fluoropyridine.; To a solution of (2-fluoro-3-pyridinyl)methanol (ASYNCHEM, 505 mg, 3.97 mmol) in dry DCM (15 ml_), under N2 atmosphere, were added triphenylphospine (ALDRICH, 1042 mg, 3.97 mmol) and carbon tetrabromide (ALDRICH, 1318 mg, 3.97mmol) in an ice-water bath. Reaction mixture was stirred at room temperature overnight. 0.3 eq. of carbon tetrabromide (ALDRICH, 409 mg, 1.19 mmol) and 0.3 eq. of triphenylphospine (ALDRICH, 323 mg, 1.19 mmol) were added. Reaction mixture was stirred untill starting material was not detected. Solvent was evaporated to dryness. Residue was purified by silica gel chromatography using a linear gradient of hexane- EtOAc. Collected fractions afforded title compound (812 mg, 4.27 mmol, quantitative yield) as yellow oil. 1 H NMR (300 MHz, DMSO-cfe) delta ppm: 8.20-8.21 (m, 1 H), 8.06-8.12 (m, 1 H), 735-7.39 (m, 1 H), 4.69 (s, 2H). [ES+ MS] m/z 190 (M).

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 131747-55-2, 2-Fluoro-3-(hydroxymethyl)pyridine.

Reference:
Patent; GLAXO GROUP LIMITED; CASTRO PICHEL, Julia; FERNANDEZ MENENDEZ, Raquel; FERNANDEZ VELANDO, Esther Pilar; GONZALEZ DEL VALLE, Silvia; MALLO-RUBIO, Araceli; WO2012/49161; (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. 884494-82-0, name is 5-Fluoro-2-methoxynicotinic acid, the common compound, a new synthetic route is introduced below. category: pyridine-derivatives

5-Fluoro-2-methoxy-pyridine-3-carboxylic acid (166 mg, 0.97 mmol) and 6-[4-[(lS)- 2,2,2-trifluoro-l-methyl-ethyl]-l,2,4-triazol-3-yl]pyridin-2-amine (250 mg, 0.97 mmol) were dissolved in triethylamine (1.35 mL, 9.72 mmol) and propylphosphonic anhydride (> 50 wt % in EtOAc, 1.0 mL). The reaction was heated at 80 C for 3 h. The reaction was cooled to rt, quenched by addition of MeOH (5 mL) and stirred for 1 h. The resulting solid was filtered and dried in vacuo to give the title compound (247 mg, 62%) as a white solid. ‘H NMR (400 MHz, CD3OD) d 9.02 (s, 1H), 8.38 (dd, 7=1.63, 7.40 Hz, 1H), 8.27 (d, 7=3.26 Hz, 1H), 8.14 – 8.21 (m, 1H), 7.97 – 8.04 (m, 2H), 6.89 (quin, 7=7.22 Hz, 1H), 4.15 (s, 3H), 1.89 (d, 7=7.28 Hz, 2H), 1.86-1.91 (m, 1H). MS (ESI): 411.1 [M + H]+.

The synthetic route of 884494-82-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BIOGEN MA INC.; GONZALEZ LOPEZ DE TURISO, Felix; DECHANTSREITER, Michael; XIN, Zhili; JONES, John, H.; HIMMELBAUER, Martin; (0 pag.)WO2020/6031; (2020); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 878197-68-3 ,Some common heterocyclic compound, 878197-68-3, molecular formula is C8H5BrN2O, 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.

Alternatively 5-(4-Methyl-1-piperazinyl)imidazo[1 ,2-a]pyridine-2-carbaldehyde can be prepared as follows: EPO A reactor is charged with 2-amino-6-bromopyridine (3.0 Kg1 17.3 mol) and dimethoxyethane ( 12 Liters) and stirred under nitrogen. 1 ,1 ,3-Trichloroacetone (5.6 Kg, 30.3 mol) is added to the 25 C solution in a single portion and the reaction solution is warmed to 65 0C jacket temperature and maintained for approximately 2 to 4 hours until judged complete. The reaction is cooled to 10 C and held for approximately one hour and filtered. The solids are rinsed with dimethoxyethane (6 Liters). The solid is placed back in the reactor and treated with dimethoxyethane (12 Liters) and 2N HCI (12 Liters) and warmed to aproximately 75 degrees for 16 to 20 hours or until judged complete. The reaction is cooled to approximately 1O0C and pH is adjusted to approximately 8 with 3 N NaOH. The resulting solids are filtered and washed with water. The solid is dried at 50 0C for 16 hours to yield 5-bromoimidazo[1 ,2-a]pyridine-2-carbaldehyde, (2.81 Kg, 72% yield) 1 H NMR (400 MHz, DMSO-D6) delta ppm 10.05 (s, 1 H) 8.66 (s, 1 H) 7.72 (s, 1 H) 7.42 (s, 1 H) 7.35 (s, 1 H). The reactor is charged with N-methylpiperazine (3.1 Kg, 31 mol ) and tetrahydrofuran (10 Liters) and stirred under nitrogen while cooling to negative 20 0C. n- Butyl lithium (10.4 L, 26.0 mol) is added to the reaction at a rate to maintain the negative 20 0C temp and the contents are stirred for 15 to 30 minutes. A slurry of 5- bromoimidazo[1 ,2-a]pyridine-2-carbaldehyde (2.79 Kg, 12.4 mol) in tetrahydrofuran (10 Liters) is added at a rate to maintain the reaction at ?0C. The slurry is washed in with additional tetrahydrofuran (6 Liters). The reaction is stirred for 30 minutes and warmed to approximately negative 10 0C. The reaction is quenched by addition of 6N HCI solution to achieve pH 4.0 while maintaining at ? 150C. The reaction is diluted with heptane (14 Liters) and the layers allowed to separate. The lower aqueous layer is drained and the upper organic layer is washed with 1 N HCI (2 x 1.5 Liters). The combined aqueous layers are stirred at 20 degrees and adjusted to pH 9 with 4N NaOH solution. The Aqueous layer is extracted with 10% iPrOH/CH2CI2 (3 x 28 Liters) and the combined organic layers are washed with saturated NaHCO3 solution (14 Liters) and evaporated at <25 0C to approximately 3 volumes, lsopropanol (28 Liters) is added and reaction again concentrated under reduced pressure to approximately 8.5 Liters, lsopropanol (17 Liters) is added and the reaction is treated with a solution of oxalic acid (1.0 Kg, 11.1 mol) in isopropanol (7 Liters) at a rate to maintain good stirring and temperature between approximately 25-4O0C. The reaction is stirred for 30 minutes and the solids are collected and washed with isopropanol (8.5 Liters) Solids are dried at 50 0C to yield 5-(4-methyl-1- piperazinyl)imidazo[1 ,2-a]pyridine-2-carbaldehyde, (2.25 Kg, 54% yield) 1 H NMR (400 MHz, DMSO-D6) delta ppm 10.01 (s, 1 H) 8.47 (s, 1 H) 7.41 (m, 2 H) 6.65 (m, 1 H) 3.34 (s, 8 H) 2.78 (s, 3 H) These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,878197-68-3, its application will become more common. Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2006/76131; (2006); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 66909-38-4, Adding some certain compound to certain chemical reactions, such as: 66909-38-4, name is 6-Chloro-4-methylpyridin-3-amine,molecular formula is C6H7ClN2, 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 66909-38-4.

To a solution of 6-chloro-4-methylpyridin-3 -amine (100 g, 701 mmol) in DMF (1000 mL) was added l-iodopyrrolidine-2,5-dione (189 g, 842 mmol) in portions. The mixture was stirred for 10 h at 25C and then concentrated under reduced pressure. The residue was diluted with water and extracted with EtOAc, washed with brine, dried (Na2S04), filtered and concentrated. The residue was purified by chromatography on Si02, eluted with petroleum ether/EtOAc (10: 1) to give 6-chloro-2-iodo-4-methylpyridin-3-amine. MS (EI) calc’d for C6H7C1IN2 [M+H]+ 269, found 269

According to the analysis of related databases, 66909-38-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; SILIPHAIVANH, Phieng; METHOT, Joey; LIPFORD, Kathryn Ann; MOLINARI, Danielle; SLOMAN, David, L.; WITTER, David; ZHOU, Hua; BOYCE, Christopher; HUANG, Xianhai; LIM, Jongwon; GUERIN, David; KARUNAKARAN, Ganesh Babu; BAKSHI, Raman Kumar; LIU, Ziping; FU, Jianmin; WAN, Zhilong; LIU, Wei; (216 pag.)WO2016/100050; (2016); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 75073-11-9, 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.75073-11-9, name is 5-Iodo-6-methylpyridin-2-amine, molecular formula is C6H7IN2, molecular weight is 234.04, as common compound, the synthetic route is as follows.

3. Take 12.20 g of compound 10 and 14.60 g of p-acetamidobenzenesulfonyl chloride (compound 4), add it to 200 mL of pyridine, and stir at room temperature for 24 h. Under vacuum, remove the organic reagents to a volume of 50 mL. 200 mL of water was added and a precipitate formed. The precipitate was filtered, washed with 200 mL of water, and dried under vacuum to obtain 9.40 g (compound 11) of a white powder with a yield of about 42%.

Statistics shows that 75073-11-9 is playing an increasingly important role. we look forward to future research findings about 5-Iodo-6-methylpyridin-2-amine.

Reference:
Patent; China Agricultural University; Wang Zhanhui; Shen Jianzhong; Wen Kai; Li Chenglong; Yu Xuezhi; Zhang Suxia; Shi Weimin; Yu Wenbo; (19 pag.)CN110713457; (2020); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 934279-60-4, 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. 934279-60-4, name is 2-Chloro-5-(trifluoromethyl)nicotinaldehyde. A new synthetic method of this compound is introduced below.

A mixture of 2-chloro-5-trifluoromethylpyridine-3-carboxaldehyde (330 mg, 1.6 mmol), trans- (/?)-2-[4-(benzyloxyethyl)cyclohexyl]pyrrolidine (410 mg, 1.5 mmol), potassium carbonate (310 mg. 2.2 mmol) in toluene (3.5 ml_) is stirred under reflux condition for 5 hours. After cooling to room temperature, water and dichloromethane are added and the mixture is extracted with dichloromethane. The combined organic layer is filtered through phase separator and concentrated. The residue is purified by silica gel column chromatography to give frans-2-{(R)-2-[4-(2-ben2yloxyethyl)cyclohexyl]pyrrolidin-1-yl}-5-trifluoromethylpyridine-3-carboxaldehyde (527 mg).0.82-1.23 (m, 4H), 1.69-1.55 (m, 4H), 1.81-1.91 (m, 3H), 1.92-2.11 (m, 3H), 2.98-3.03 (m,1H), 3.23 (d, 2H), 3.65-3.72 (m, 1H), 4.48 (s, 2H), 4.52-4.70 (m, 1H), 7.32 (s, 1H), 7.25-7.37(m, 5H), 8.11 (d, 1H), 8.50 (d, 1H), 9.93 (s. 1H).Rf value: 0.41 (Hexane/EtOAc = 9/1 )

At the same time, in my other blogs, there are other synthetic methods of this type of compound,934279-60-4, 2-Chloro-5-(trifluoromethyl)nicotinaldehyde, and friends who are interested can also refer to it.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2007/73934; (2007); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 6945-67-1, Adding some certain compound to certain chemical reactions, such as: 6945-67-1, name is 2-Bromo-4-nitropyridine,molecular formula is C5H3BrN2O2, 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 6945-67-1.

The 2-bromo-4-nitropyridine (200mg, 0.99mmol),4-hydroxypiperidine (149.48mg, 1.48mmol) and cesium carbonate(642.02mg, 1.97mmol) placed in the reaction flask, add 20mL 1,4-Dioxane, react overnight at 100C. The reaction is over,Cool to room temperature, filter,The filtrate was concentrated and purified by column chromatography to obtain the title compound.

According to the analysis of related databases, 6945-67-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Nanjing Shenghe Pharmaceutical Co., Ltd.; Wang Yong; Zhao Liwen; Wang Yazhou; Quan Xu; Liu Haixuan; Wang Xiaowei; Zhang Yan; Li Xue; Cao Chen; Guo Zhuang; Lv Kunzhi; Wang Hai; Zheng Guochuang; (126 pag.)CN111196804; (2020); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 183428-91-3, 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 183428-91-3, name is 2-Amino-3-methyl-5-cyanopyridine. This compound has unique chemical properties. The synthetic route is as follows.

Step II: 6-Amino-5-methyl-pyridme-3-carboxylic acidTo a stirred suspension of 6-amino-5-methyl-pyridine-3-carbonitrile (6.0 g, 45.0 mmol) in water (40 mL) was added sodium hydroxide (5.4 g, 135.2 mmol) and refluxed for 4 h. Reaction mixture was cooled to room temperature and filtered through Buchner funnel. Filtrate was neutralized with 4N HC1. Solid formed was filtered through Buchner funnel and dried under high vacuum to furnish 6.0 g (88%) of titled intermediate as a white solid.? NMR (400 MHz, CDC13): delta 2.05 (s, 3H), 6.53 (s, 2H), 7.66 (s, 1H), 8.37 (d, J = 2.0 Hz, 1H), 12.29 (brs, 1H). MS (ES) m/z 153.0 (M+l).

According to the analysis of related databases, 183428-91-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ADVINUS THERAPEUTICS LIMITED; KHARUL, Rajendra; BHUNIYA, Debnath; MOOKHTIAR, Kasim A.; SINGH, Umesh; HAZARE, Atul; PATIL, Satish; DATRANGE, Laxmikant; THAKKAR, Mahesh; WO2013/42139; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem