Pyridine-derivatives

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.911434-05-4, name is 5-Bromo-2-methyl-3-nitropyridine, molecular formula is C6H5BrN2O2, molecular weight is 217.02, as common compound, the synthetic route is as follows.Recommanded Product: 911434-05-4

j00130j 5-Bromo-2-methyl-3-nitropyridine (2.00 g, 9.22 mmol) was dissolved in THF (92 mL) and the solution was cooled to -50 C under an atmosphere of argon. Vinylmagnesium bromide (1 M in THF, 27.6 mL, 27.6 mmol) was added in one portion and the reaction mixture turned orange. The reaction was allowed to stir at -40 C for 30 mm and then quenched the reaction with saturated ammonium chloride solution. The mixture was extracted with EtOAc, the combined organic layers dried with MgSO4 and concentrated by rotary evaporation. The crude material was purified by column chromatography to yield 4-bromo-7-methyl-1H-pyrrolo[2,3-c]pyridine (0.711 g, 36.6%). LCMS (FA): m/z = 211.0, 213.0 (M+H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,911434-05-4, 5-Bromo-2-methyl-3-nitropyridine, and friends who are interested can also refer to it.

Reference:
Patent; MILLENNIUM PHARMACEUTICALS, INC.; BHARATHAN, Indu T.; BLACKBURN, Chris; CIAVARRI, Jeffrey P.; CHOUITAR, Jouhara; CULLIS, Courtney A.; D’AMORE, Natalie; FLEMING, Paul E.; GIGSTAD, Kenneth M.; GIPSON, Krista E.; GIRARD, Mario; HU, Yongbo; LEE, Janice; LI, Gang; REZAEI, Mansoureh; SINTCHAK, Michael D.; SOUCY, Francois; STROUD, Stephen G.; VOS, Tricia J.; XU, He; YE, Yingchun; WO2015/108881; (2015); 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.15128-82-2, name is 2-Nitropyridin-3-ol, molecular formula is C5H4N2O3, molecular weight is 140.1, as common compound, the synthetic route is as follows.name: 2-Nitropyridin-3-ol

(Example 2 Synthesis of Compounds I-113 and 1-144) [Show Image]Step 1 A solution of 2-nitropyridin-3-ol (6) (16.0 g, 114 mmol) in dimethylformamide (120 mL) was cooled to 0C, and then N-bromosuccinimide (26.4 g, 1.48 mmol) was gradually added thereto. The solution was then stirred at 0 C for 1 hour, and at room temperature for another 2 hours. The reaction solution was concentrated in vacuo, and then the residue was washed with diethyl ether. The filtrate was poured to aqueous saturated sodium bicarbonate, followed by extraction with diethyl ether. The organic layer was washed sequentially with water and saturated brine, then dried with anhydrous magnesium sulfate, and concentrated in vacuo to yield the subject compound (7) (15.5 g, 62%) as a white powder.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,15128-82-2, 2-Nitropyridin-3-ol, and friends who are interested can also refer to it.

Reference:
Patent; Shionogi & Co., Ltd.; EP2341052; (2011); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 6345-27-3 , The common heterocyclic compound, 6345-27-3, name is Isonicotinimidamide hydrochloride, molecular formula is C6H8ClN3, 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.

Isonicotinamidine hydrochloride (5.0Og, 31.7mmol) and acetaldehyde dimethylacetal (8.44mL, 63.5mmol) were combined and heated to 1100C in anhydrous DMF (35mL) in the presence of DBU (14.2OmL, 95.2mmol) for 3h. The reaction mixture was cooled to 200C, then stirred for 16h, before being concentrated in vacuo. The residue was partitioned between H2O(10OmL) and EtOAc (10OmL). The aqueous layer was extracted with EtOAc (2x50mL), then the combined organics were washed with brine (5OmL), dried (MgSO4), filtered and concentrated under reduced pressure. Flash column chromatography (EtOAc) of the residue gave 4-methyl-2-pyridin-4-yl-pyrimidine: deltaH ((CDj)2SO): 2.57 (3H, s), 7.45 (IH, d), 8.21-8.26 (2H, m), 8.72-8.77 (2H, m), 8.82 (IH, d). To a solution of this compound (1.06g, 6.17mmol) in anhydrous dioxane (2OmL) was added SeO2 (2.05g, 18.51mol), then the mixture was heated to reflux for 9Oh. The reaction mixture was cooled to 200C then filtered, washing with EtOAc. The filtrate was evaporated to dryness, then the residue was suspended in CH2Cl2. The suspension was filtered, washing with CH2Cl2, then the filtrate was evaporated to dryness to furnish the title compound: deltaH (CDCl3): 7.80 (IH, d), 8.38 (2H, d), 8.83 (2H, d), 9.13 (IH, d),10.15 (IH, s).

The synthetic route of 6345-27-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PROSIDION LTD.; WO2006/70208; (2006); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 131803-48-0, Methyl 6-(bromomethyl)nicotinate, 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, 131803-48-0, blongs to pyridine-derivatives compound. COA of Formula: C8H8BrNO2

Example II (0492) 6-{[Bis(pyrazin-2-yl)amino]methyl}-N-hydroxypyridine-3-carboxamide (0493) (0494) II (0495) NaH (60%, 48.5mg, 1.21 mmol) was added to a solution of (3) (200mg, 1.15mmol) in DMF (7ml_) at 5C under N2(g). The reaction mixture was stirred for 20min then methyl 6-(bromomethyl)pyridine-3-carboxylate (345mg, 1.5mmol) was added as a solution in DMF (3ml_). The stirring was continued at 70C for 1 h. Reaction cooled to rt and poured onto water (100ml_). Brine (25ml_) was added and the aqueous was extracted with EtOAc (2 x 100ml_). Combined organics were dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by flash column chromatography with CH2CI2/EtOAc (1 :0-0:1) then EtOAc/MeOH (1 :0-4: 1) to give (4) (129mg, 35%). (0496) 1 H NMR (500 MHz, Chloroform-d), deltaEta ppm: 9.04-9.13 (m, 1 H), 8.70 (s, 2H), 8.19 (s, 2H), 8.13 (dd, J=5.6, 2.3 Hz, 3H), 7.32 (d, J=8.2 Hz, 1 H), 5.55 (s, 2H), 3.86 (s, 3H). LCMS (ES): Found 322.9 [M+H]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,131803-48-0, its application will become more common.

Reference:
Patent; KARUS THERAPEUTICS LTD; SHUTTLEWORTH, Stephen Joseph; WHALE, Andrew David; COLMAN, Lucy Mary; ROGERS, Helen Louise; (117 pag.)WO2017/208032; (2017); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 119830-47-6 ,Some common heterocyclic compound, 119830-47-6, molecular formula is C8H10N2O2, 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 Preparation of 5-(2-(2-chloro-4-fluorophenoxy)-6-(trifluoromethyl)benzamido)picolinic acid (74) [embedded image] To a solution of 2-chloro-4-fluoro-phenol (20.97 g, 143.10 mmol) and 2-fluoro-6-(trifluoromethyl)benzaldehyde (25 g, 130.1 mmol) in DMF (125.0 mL) was added Cs2CO3 (46.62 g, 143.1 mmol) and the reaction mixture was stirred at 100 C. for 1 hour. The reaction mixture was poured into water (500 ml) and extracted with ethyl acetate (3150 ml). The organics were combined, washed with water, brine (2), dried over Na2SO4, filtered and evaporated to give a red oil which solidified after standing over night. The material was then triturated with hot hexanes and cooled to 25 C. The slurry was filtered and washed with cold hexanes to give 2-(2-chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzaldehyde (32.7 g, 79%) as an off white solid. 1H NMR (400 MHz, DMSO) – 10.61 (s, 1H), 7.84-7.70 (m, 2H), 7.66 (d, J=7.9 Hz, 1H), 7.47 (dd, J=9.0, 5.3 Hz, 1H), 7.42-7.32 (m, 1H), 7.12 (d, J=8.3 Hz, 1H) ppm.To a solution of 2-(2-chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzaldehyde (31 g, 97.29 mmol) in tBuOH (155.0 mL), water (100.8 mL), CH3CN (155.0 mL) and 2-methyl-2-butene (51.45 mL, 486.4 mmol) was added sodium dihydrogen phosphate (35.02 g, 291.9 mmol) and the mixture was cooled to 0 C. Sodium chlorite (26.40 g, 291.9 mmol) was added in one portion and the mixture was stirred at 25 C. for 1 hour. The pH of the reaction was adjusted to 2-3 with 1N HCl and the layers were separated. The aqueous layer was extracted with EtOAc (3). All the organic layers were combined, and solid sodium sulfite (-5 g) was added followed by brine (50 ml) and 1N NaOH (10 ml) and the mixture was shaken until the yellow color disappeared. The layers were separated and the organic was washed with brine, dried over Na2SO4, filtered through a short plug of silica and evaporated to dryness to give 2-(2-chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzoic acid (40 g, 98%) as an oil that was used in the next step without further purification. ESI-MS m/z calc. 334.00. found 335.1 (M+1)+. Retention time: 1.58 minutes (3 minutes run).A solution of 2-(2-chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzoic acid (33.46 mg, 0.10 mmol), ethyl 5-aminopyridine-2-carboxylate (19.94 mg, 0.12 mmol), HATU (41.83 mg, 0.11 mmol) and N-methylmorpholine (21.99 -L, 0.20 mmol) was stirred at 100 C. for 8 hours. NaH (16.00 mg, 0.40 mmol) was added and the mixture was stirred at 100 C. for 10 min. The mixture was filtered and purified by reverse phase HPLC using a gradient of acetonitrile in Water (1-99%) and HCl as a modifier, to give 5-[[2-(2-chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzoyl]amino]pyridine-2-carboxylic acid (74) (2.52 mg, 5%) as a white solid. ESI-MS m/z calc. 454.03. found 455.3 (M+1)+. Retention time: 1.42 minutes (3 minutes run).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,119830-47-6, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; Hadida-Ruah, Sara Sabina; Anderson, Corey; Arumugam, Vijayalaksmi; Asgian, Iuliana Luci; Bear, Brian Richard; Termin, Andreas P.; Johnson, James Philip; US2014/221435; (2014); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 13362-26-0 ,Some common heterocyclic compound, 13362-26-0, molecular formula is C8H10N2O2, 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 13 Synthesis of ethyl 2-ethoxycarbonyl-imidazo[1,2-a]pyridine-8-carboxylate (Compound No. 1-123) A mixture of ethyl bromopyruvate (2.3 g, 10.2 m mol and ethyl 2-aminonicotinate (1.7 g, 10 m mol) in methyl ethyl ketone (17 ml) was refluxed for 5 hours. After completion of the reaction, the mixture was cooled to room temperature and distilled under reduced pressure to remove the solvent. The residue to which saturated sodium hydrogen carbonate aqueous solution (50 ml) was added was extracted with chloroform (100 ml*3). The extract was washed with water, dried over MgSO4 and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate) to give the object compound (0.7 g, yield 26.7%) as crystals. m.p. 97 C.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,13362-26-0, its application will become more common.

Reference:
Patent; Takeda Chemical Industries, Ltd.; US5498774; (1996); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 504-29-0, 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 504-29-0, name is Pyridin-2-amine. This compound has unique chemical properties. The synthetic route is as follows.

Manufacturing Example 1-2-1: 2,2-Dimethyl-N-pyridin-2-yl-propionamide To a methylene chloride (500 mL) solution of 2-aminopyridine (50 g) were added triethylamine (81 mL) and pivaloyl chloride (72 mL) at 0C, which was stirred for 4 hours and 30 minutes at room temperature. Water was added to the reaction solution, and then extraction was performed with methylene chloride. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate and filtered, and then the filtrate was concentrated under a reduced pressure. Potassium carbonate (73 g) was added at 0C to a methanol (300 mL) solution of the residue thus obtained, which was stirred for 90 minutes at room temperature. Water was added to the reaction solution, and then extraction was performed with ethyl acetate. The organic layer was washed with saturated brine, then dried over anhydrous magnesium sulfate, and filtered, after which the filtrate was concentrated under a reduced pressure. Heptane (300 mL) was added to the residue, and the precipitated solids were filtered off to obtain the titled compound (80 g). The filtrate was then further concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate = 2:1) to obtain the titled compound (12 g). 1H-NMR spectrum (DMSO-d6) delta (ppm): 1.22 (9H, s), 7.06-7.09 (1H, m), 7.72-7.77 (1 H, m), 8.01-8.03 (1 H, m), 8.29-8.31 (1 H, m), 9.71 (1 H, s).

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 504-29-0, Pyridin-2-amine.

Reference:
Patent; Eisai R&D Management Co., Ltd.; EP2065377; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 98027-84-0, 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.98027-84-0, name is 2,6-Dichloro-4-iodopyridine, molecular formula is C5H2Cl2IN, molecular weight is 273.8866, as common compound, the synthetic route is as follows.

2,6-Dichloro-4-iodo-pyridine (1 g, 3.65 mmol), N-[4-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)-2-pyridyl]acetamide (1 .2 g, 4.58 mmol), PdCI2(PPh3)2 (128 mg, 0.18 mmol) and K2CO3 (1 .51 g, 10.95 mmol) were taken up in 1 ,4- dioxane:H2O:EtOH (6:3:1 , 15 ml) and nitrogen was bubbled through the mixture for 5 min before being heated to 80 C for 2 h. When cooled to rt water (10 ml), brine (10 ml) and EtOAc (25 ml) were added, the mixture stirred vigorously for 5 min and the organic layer was separated. The aqueous layer was extracted with EtOAc (3 x 20 ml) and the combined organics were washed with brine, dried over Na2SO4, filtered andconcentrated. Recrystallization from MeCN gave the product as a solid (760 mg, 74%). MS ES+ m/z 282 [M+H]+.

Statistics shows that 98027-84-0 is playing an increasingly important role. we look forward to future research findings about 2,6-Dichloro-4-iodopyridine.

Reference:
Patent; SPRINT BIOSCIENCE AB; LINDSTROeM, Johan; FORSBLOM, Rickard; GINMAN, Tobias; RAHM, Fredrik; VIKLUND, Jenny; (89 pag.)WO2019/38387; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 147149-98-2, 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 147149-98-2, name is 4-Amino-2-(trifluoromethyl)pyridine. This compound has unique chemical properties. The synthetic route is as follows.

4) Methyl 2-methyl-2-[3-(2-trifluoromethylpyridin-4-yl)ureido]propionate 65.6 3.8 ml of a solution of phosgene in toluene (20%) were initially charged under argon. At 75 C., 0.58 g of compound 65.5 dissolved in 20 ml of dry acetonitrile was slowly added dropwise; the mixture was then stirred at 80 C. for 4 h. The mixture was repeatedly concentrated with toluene under reduced pressure. The residue was dissolved in 20 ml of dry tetrahydrofuran and admixed with 0.55 g of methyl amino-isobutyrate hydrochloride. 0.76 ml of triethylamine was slowly added dropwise to this mixture which was then stirred at room temperature for 4 h and then left to stand overnight. The reaction mixture was admixed with water and extracted with ethyl acetate. The organic phase was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel with 95/5 dichloromethane/methanol. The urea 65.6 was obtained in 59% yield. Molecular weight 305.09 (C12H14F3N3O3); retention time Rt=1.66 min. [B]; MS (ESI): 306.44 (MH+).

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 147149-98-2, 4-Amino-2-(trifluoromethyl)pyridine.

Reference:
Patent; SANOFI-AVENTIS; US2009/215728; (2009); 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. 15862-37-0, name is 2,5-Dibromo-3-nitropyridine. A new synthetic method of this compound is introduced below., Formula: C5H2Br2N2O2

tert-Butyl 4-[(5-bromo-3-nitropyridin-2-yl)amino]piperidine-1-carboxylate. 2,5-Dibromo-3-nitropyridine (0.200 g, 0.71 mmol) was dissolved in DMSO (3 mL) and treated with 4-amino-1-boc-piperidine (0.428 g, 2.14 mmol.) The mixture was heated at 80 C. overnight and then diluted with ethyl acetate (30 mL.) The organic solution was washed with water (3*25 mL), saturated sodium bicarbonate (25 mL) and brine (25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by automated flash silica gel chromatography (ISCO Redi-Sep column) eluding with 0-100% ethyl acetate/hexane to yield the title compound. 0.229 g (80%). HPLC (method A): Rt=11.2 min. MS: [M+H-t-butyl]+=344.8.

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, 15862-37-0, 2,5-Dibromo-3-nitropyridine.

Reference:
Patent; Wyeth; US2009/69319; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem