Category: pyridine-derivatives

Electric Literature of 866775-18-0, 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 866775-18-0, name is Methyl 3-amino-6-bromo-5-(trifluoromethyl)picolinate. This compound has unique chemical properties. The synthetic route is as follows.

Intermediate A: 3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (1.40 g, 4.68 mmol) was suspended in MeOH (15 ml); Sodium hydroxide (2.0 M aqueous solution) (14.04 ml, 28.1 mmol) was added and the suspension was stirred at RT overnight. The mixture was concentrated in vacuo and the resulting residue was dissolved in water (100 ml) and then acidifed by the addition of 5.0M HCl(aq). The product was extracted into ethyl acetate (2×75 ml) and the combined organic extracts were washed with water (50 ml), brine (25 ml), dried (MgSO4) and concentrated in vacuo to afford the title product as a yellow solid. 1H-NMR: [400 MHz, DMSO-d6, deltaH 13.24 (1H, br s, CO2H), 7.74 (1H, s, ArH), 7.17 92H, br s ArNH2). m/z 285.1, 287.1 [M+H]+

According to the analysis of related databases, 866775-18-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NOVARTIS AG; US2011/230483; (2011); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 54903-86-5, 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. 54903-86-5, name is 3-Bromopyridine-2,6-diamine. A new synthetic method of this compound is introduced below.

Preparation of N-(6-amino-5-bromo(2-pyridyl))(2-fluorophenyl)carboxamide (61): A solution of 3-bromo-2,6-diaminopyridine (60) (564 mg, 3 mmol), triethyl amine (0.54 ml) in DCM (6 ml)/THF (4 ml) was cooled down to -78 C. A solution of 2-fluorobenzoyl chloride (362 mul, 3.03 mmol) in 2 ml DCM was added dropwise within 10 min. The resulting reaction mixture was stirred at -78 C. for 1 h before slowly warm up to r.t. After stirred at r.t. for 3 h, the reaction quenched with aq NaHCO3 solution. 200 ml EA were added. Org. phase was washed with brine, dried over sodium sulfate, concentrated. The light yellow solid residue was triturated with DCM (ca. 15 ml), filtered and dried to give 530 mg N-(6-amino-5-bromo(2-pyridyl))(2-fluorophenyl)carboxamide (61) as white solid. (purity>95%, yield: 57%).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,54903-86-5, 3-Bromopyridine-2,6-diamine, and friends who are interested can also refer to it.

Reference:
Patent; CalciMedica, Inc.; US2011/263612; (2011); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 851386-40-8, Adding some certain compound to certain chemical reactions, such as: 851386-40-8, name is 4-Chloro-2,5-difluoropyridine,molecular formula is C5H2ClF2N, 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 851386-40-8.

4-chloro-2,5-difluoropyridine E2 (1 .00 equivalents), 4-cyano-phenylboronic acid (1 .20 equivalents), Pd2(dba)3 (0.02 equivalent), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (SPhos) (0.08 equivalents) and tribasic potassium phosphate (2.50 equivalents) are stirred under nitrogen atmosphere in a dioxane/water mixture (ratio of 10:1 ) at 1 10 C for 20 h. To the reaction mixture Celite and active carbon are added and stirred at 1 10C for 15 min. Subsequently the reaction mixture is hot filtered and the residue washed with dioxane. The reaction mixture is poured into 200 mL of a saturated sodium chloride solution and extracted with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over MgSC>4 and the solvent is evaporated under reduced pressure. The crude product obtained is purified by recrystallization in cyclohexane and the product obtained as solid. (0422) Instead of a boronic acid a corresponding boronic acid ester may be used.The synthesis of Z3 is carried out according to AAV1-1, wherein 4-chloro-2,5-difluoropyridine E2 reacts with 3-cyano-phenylboronic acid ester. eneral procedure for synthesis AAV2-1:

According to the analysis of related databases, 851386-40-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CYNORA GMBH; ESTEBAN, Alhama Arjona; (133 pag.)WO2018/189356; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 709652-82-4, 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.709652-82-4, name is 2-Amino-5-bromonicotinonitrile, molecular formula is C6H4BrN3, molecular weight is 198.0201, as common compound, the synthetic route is as follows.

To a microwave reaction vessel were added 4-(tert- butoxycarbonylamino)phenylboronic acid (180 mg, 0.759 mmol), 5-bromo-3-cyano- 2-aminopyridine (170.0 mg, 0.858 mmol), 1,4-dioxane (3.5 mL) and 2M aqueous sodium carbonate (0.94 mL, 1.88 mmol). Argon gas was bubbled through the solution for 5 min, then tetrakis(triphenylphosphine) palladium(O) (40.0 mg, 0.035 mmol) was added and the vial was sealed and heated in a microwave reactor for 20 min at 170 C. The mixture was partitioned between EtOAc (10 mL) and saturated sodium bicarbonate (10 mL) The aqueous layer was separated and extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried over MgS04, filtered and concentrated under reduced pressure to give an oil which was purified by silica gel flash chromatography, eluting with 25-100% EtOAc in hexanes. The purified material was dissolved in DCM (4 mL), excess TFA (2 mL) added and the mixture was stirred at rt for 4 h. The mixture was concentrated to dryness, then EtOAc (8 mL), saturated NaHC03 (8 mL) and 1 M aqueous NaOH (1 mL) were added. After confirming basic pH, the layers were shaken and separated and the aqueous layer was extracted with EtOAc (2 x 5 mL). The combined extracts were dried over MgS04, filtered and concentrated under reduced pressure to give 2- amino-5-(4-aminophenyl)nicotinonitrile (113.9 mg, 71%) as a solid, which was sufficiently pure for the next step. LC-MS (ESI) m/z 2 (M +H)+.

Statistics shows that 709652-82-4 is playing an increasingly important role. we look forward to future research findings about 2-Amino-5-bromonicotinonitrile.

Reference:
Patent; AMBIT BIOSCIENCES CORPORATION; ABRAHAM, Sunny; HOLLADAY, Mark, W.; LIU, Gang; XU, Shimin; WO2011/22473; (2011); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 79055-63-3, 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. 79055-63-3, name is 2-Chloro-6-methylpyridin-4-amine. A new synthetic method of this compound is introduced below.

To a flask was added 2-chloro-4-(trifluoromethyl)-pyrimidine (1.50 g, 8.22 mmol), 2-chloro-6-methylpyridin-4-amine (1.17 g, 8.22 mmol), palladium acetate (0.18 g, 0.82 mmol), Xantphos (0.95 g, 1.64 mmol), and cesium carbonate (5.36 g, 16.44 mmol) followed by 1,4-dioxane (16.44 mL). The mixture was stirred at 100 C for 2 hours. The reaction was cooled to room temperature and was diluted with ethyl acetate and aqueous sodium bicarbonate solution and extracted with ethyl acetate. The combined organic fractions were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0-50% ethyl acetate/hexanes) to afford N- (2-chloro-6-methylpyridin-4-yl)-4-(trifluoromethyl)pyrimidin-2-amine as a pale yellow solid. MS ESI calcd. for C11H9CIF3N4 [M + H]+ 289, found 289. XH NMR (500 MHz, DMSO-d6) delta 10.82 (s, 1H), 8.96 (d, J= 5.0 Hz, 1H), 7.78 (d, J= 1.5 Hz, 1H), 7.50 (d, J= 1.5 Hz, 1H), 7.48 (d, J= 5.0 Hz, 1H), 2.37 (s, 3H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,79055-63-3, 2-Chloro-6-methylpyridin-4-amine, and friends who are interested can also refer to it.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MERCK CANADA INC.; ANTHONY, Neville, J.; ANDRESEN, Brian, M.; NORTHRUP, Alan, B.; CHILDERS, Kaleen, K.; DONOFRIO, Anthony; MILLER, Thomas, A.; LIU, Yuan; MACHACEK, Michelle, R.; WOO, Hyun Chong; SPENCER, Kerrie, B.; ELLIS, John Michael; ALTMAN, Michael, D.; ROMEO, Eric, T.; GUAY, Daniel; GRIMM, Jonathan; LEBRUN, Marie-Eve; ROBICHAUD, Joel, S.; WANG, Liping; DUBOIS, Byron; DENG, Qiaolin; WO2014/176210; (2014); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 122306-01-8, 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.122306-01-8, name is (6-Bromopyridin-3-yl)methanol, molecular formula is C6H6BrNO, molecular weight is 188.02, as common compound, the synthetic route is as follows.

Reference Example 16; 2-bromo-5-(chloromethyl)pyridine hydrochloride 2-Bromo-5-(hydroxymethyl)pyridine (2.64 g) was dissolved in THF (70 mL) and, after ice-cooling, thionyl chloride (5.11 mL) was added dropwise. The reaction mixture was stirred at the same temperature for 30 min, and concentrated. The obtained residue was washed with diethyl ether to give the title compound (2.65 g) as yellow crystals.1H-NMR (CDCl3) delta: 4.55 (2H, s), 7.52 (1H, d), 7.63 (1H, dd), 8.40 (1H, d).

Statistics shows that 122306-01-8 is playing an increasingly important role. we look forward to future research findings about (6-Bromopyridin-3-yl)methanol.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; US2009/270359; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 913839-73-3, name is 2-(6-(Trifluoromethyl)pyridin-3-yl)acetic acid. This compound has unique chemical properties. The synthetic route is as follows. name: 2-(6-(Trifluoromethyl)pyridin-3-yl)acetic acid

56C. Preparation of N’-(5-bromo-4-(4-chlorophenyl)pyridin-2-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)acetohydrazide; To a suspension of 5-bromo-4-(4-chlorophenyl)-2-hydrazinylpyridine (37 mg, 0.12 mmol), 2-(6-(trifluoromethyl)pyridin-3-yl)acetic acid (26 mg, 0.12 mmol) and bromotripyrrolidinophosphonium hexafluorophosphate (PyBop, 70 mg, 0.13 mmol) in CH3CN (1.0 mL) was added (i-Pr)2EtN (32 mg, 0.25 mmol) at 20° C. The reaction mixture was stirred at 20° C. under argon for 15 h, then concentrated in vacuo. The residue was dissolved in EtOAc (15 mL). The organic solution was successively washed with saturated aqueous NaHCO3 (5 mL) and saturated aqueous NaCl (5 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified using reverse phase preparative HPLC (Conditions: Phemomenex Luna 5mu C18 30.x.75 mm; Eluted with 0percent to 100percent B, 10 min gradient, 100percent B hold for 2 min, (A=90percent H2O, 10percent CH3CN, 0.1percent trifluoroacetic acid and B=10percent H2O, 90percent CH3CN, 0.1percent trifluoroacetic acid); Flow rate at 40 mL/min, UV detection at 220 nm), followed by basification with 1N aqueous NaOH to pH 12 and extraction with EtOAc to afford 54 mg (92percent) of the title compound as a white solid. LC/MS (method B): retention time=1.91 min, [M+H]+=487.0.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it, 913839-73-3, 2-(6-(Trifluoromethyl)pyridin-3-yl)acetic acid.

Reference:
Patent; Sun, Chongqing; Huang, Yanting; Sitkoff, Doree F.; Lee, Taekyu; Ewing, William; US2006/287324; (2006); 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. 21190-87-4, name is 6-Bromo-2-pyridinecarboxylic acid, the common compound, a new synthetic route is introduced below. COA of Formula: C6H4BrNO2

A) 6-(4-Fluorophenyl)picolinic acid A solution of 6-bromopicolinic acid (Aldrich) (2.02 g, 10 mmol) in DME containing 4 mL of 10% aq Na2CO3 was purged with Ar gas. To this mixture was added Pd(PPh3)4 followed by 2-(4-fluorophenyl)-5,5-dimethyl-1,3,2-dioxaborinane (2.40 g, 11.5 mmol, Wako Pure Chemical Industries, Ltd) and EtOH (20 mL), and the mixture was purged with Ar gas. The reaction mixture was heated at 100 C. for 2.5 h in a sealed tube. Additional 2-bromopicolinic acid (900 mg) and Pd (OAc)2 was added, and after purging with Ar gas it was heated at 100 C. for 4.5 h. Trifluoroacteic acid (20 mL) was added to the reaction mixture, concentrated and MeOH (150 mL) was added to the residue. The insoluble material was filtered, and the filtrate solution was concentrated. Purification by flash column on silica gel eluding with EtOAc/MeOH//900:100 followed by EtOAc/MeOH/HOAc//700:1500:50 provided the desired product (1.0 g, 40% based on borinane starting material) as a white solid. 1H NMR (CD3OD) delta8.01 (d, 1H, J=7.7 Hz), 7.94-7.87 (m, 3H), 7.73 (d, IH, J=7.7 Hz), 7.13 (t, 2H, 8.8 Hz); MS(ESI+) m/z 234 (M+H)+.

The synthetic route of 21190-87-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Bristol-Myers Squibb Company; US2007/60613; (2007); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 1044872-40-3, Adding some certain compound to certain chemical reactions, such as: 1044872-40-3, name is Methyl 2-amino-4,6-dichloronicotinate,molecular formula is C7H6Cl2N2O2, 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 1044872-40-3.

A mixture of dimethyl acetone-1,3-dicarboxylate (200 g, 1.15 mol), cyanamide (48.3 g, 1.15 mol), and Ni(acac)2 (14.75 g, 0.0574 mol) in dioxane (200 mL) was heated to reflux for 16 h and then cooled to room temperature. The precipitate was filtered off, and the solid was mixed with methanol (200 mL) and stirred for 30 min and filtered again to give 93 g product (44% yield). In a 1 L flask with a reflux condenser was added the product from step one (93.0 g, 0.505 mol) and POCl3 (425 mL) and the reaction mixture was heated to reflux for 35 min. POCl3 (300 mL) was evaporated under vacuum. The residue was poured into ice and water (400 mL), which was neutralized with KOH to pH 6-7. The precipitate was filtered off and extracted with ethyl acetate (2×300 mL). The organic solution was concentrated and purified by column chromatography to give methyl 2-amino-4,6-dichloropyridine-3-carboxylate (22.5 g, 20.1%). In a 500 mL flask with reflux condenser was added methyl 2-amino-4,6-dichloropyridine-3-carboxylate (22.5 g, 0.101 mol) and 25 wt % sodium methoxide in methanol (88 mL, 0.407 mol), together with methanol (20 mL). The mixture was heated to reflux for 5 h then cooled to room temperature. Acetic acid (15 mL) was added to the mixture and the pH was adjusted to 7.0. Methanol was removed and the residue was poured into water (100 mL). The precipitated solid was filtered off and rinsed with water (3×200 mL) to give methyl 2-amino-4,6-dimethoxypyridine-3-carboxylate (18.5 g, 86.4%). In a 500 mL flask with a reflux condenser was added methyl 2-amino-4,6-dimethoxypyridine-3-carboxylate (18.5 g, 0.0872 mol), potassium hydroxide (19.5 g, 0.349 mol) in water (80 mL) and ethanol (100 mL). The mixture was heated to 80 C. for 16 h. The solvent was removed and aqueous HCl was used to adjust pH to 6.0. The water was removed by lyophilization. The obtained solid was extracted with methanol to yield 2-amino-4,6-dimethoxy-nicotinic acid in quantitative yield. 2-Amino-4,6-dimethoxy-nicotinic acid (17.2 g, 0.0872 mol) was added to THF (110 mL). 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (21.73 g, 0.113 mol), 1-hydroxybenzotriazole hydrate (12.96 g, 0.0959 mol) and 4-methyl morpholine (9.7 g, 0.0959 mol) were then added to the suspension. After stirring for 10 min at room temperature, 50% v/v ammonium hydroxide (18.3 g, 0.262 mol) was added. The reaction mixture was kept at room temperature for 16 h. THF was removed and the residue was poured into cold water (100 mL). The precipitate was filtered off and further washed with cold water to yield 5.3 g of the pure desired compound. The aqueous solution was further extracted with dichloromethane (3×150 mL) to yield 8.4 g crude product, which was further purified by column chromatography to give a total of 10.8 g (62.8%) of 2-amino-4,6-dimethoxy-nicotinamide.To a solution of 2-amino-4,6-dimethoxy-nicotinamide (1.40 g, 7.1 mmol) and 4-hydroxy-3,5-dimethylbenzaldehyde (1.07 g, 7.1 mmol) in N,N-dimethyl acetamide (20 mL), NaHSO3 (1.39 g, 7.81 mmol) and p-TSA (0.675 g, 3.55 mmol) were added and the reaction mixture was heated at 150 C. overnight. The solvent was removed under reduced pressure. The residue was diluted with water and the solid was collected and further washed with methanol. The crude product was purified by column chromatography (silica gel 230-400 mesh; 2% methanol in CH2Cl2 as eluent) to give 2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H)-one (0.92 g, 39.6%). Selected data: MS (ES) m/z: 328.07; MP 297-299 C.

According to the analysis of related databases, 1044872-40-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Wong, Norman C.W.; Tucker, Joseph E.L.; Hansen, Henrik C.; Chiacchia, Fabrizio S.; McCaffrey, David; US2008/188467; (2008); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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. 1254163-81-9, name is Methyl 6-chloro-5-cyanopicolinate. A new synthetic method of this compound is introduced below., HPLC of Formula: C8H5ClN2O2

Step 2: Preparation of 5-cyano-6-(1 ,3,5-trimethyl-1 H-pyrazol-4-yl)-pyridine-2- carboxylic acid methyl esterThe title compound may be prepared from 6-chloro-5-cyano-pyridine-2-carboxylic acid methyl ester by reaction with 1 ,3,5-trimethylpyrazol-4-yl boronic acid under Suzuki reaction conditions as described in the previous examples

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it, 1254163-81-9, Methyl 6-chloro-5-cyanopicolinate.

Reference:
Patent; NOVARTIS AG; ASTEX THERAPEUTICS LIMITED; HOWARD, Steven; MORTENSON, Paul Neil; HISCOCK, Steven Douglas; WOOLFORD, Alison Jo-Anne; WOODHEAD, Andrew James; CHESSARI, Gianni; O’REILLY, Marc; CONGREVE, Miles Stuart; DAGOSTIN, Claudio; CHO, Young Shin; YANG, Fan; CHEN, Christine Hiu-Tung; BRAIN, Christopher Thomas; LAGU, Bharat; WANG, Yaping; KIM, Sunkyu; GRIALDES, John; LUZZIO, Michael Joseph; PEREZ, Lawrence Blas; WO2010/125402; (2010); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem