Category: 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.109345-94-0, name is 5-Methoxypyridin-3-ol, molecular formula is C6H7NO2, molecular weight is 125.13, as common compound, the synthetic route is as follows.COA of Formula: C6H7NO2

Step 1 3-(2-((3R,4aR,6aS,7R,10bR)-3-cyclopentyl-6a,10b-dimethyl-8-dihydromethylene decahydro-1H-naphtho[2,1-d][1,3]dioxin-7-yl)ethoxy)-5-methoxypyridine (3R,4aR,6aS,7R,10bR)-7-(2-bromoethyl)-3-cyclopentyl-6a,10b-dimeth yl-8-dihydromethylene decahydro-1H-naphtho[2,1-d][1,3]dioxin (1.00 g, 2.43 mmol) was dissolved in N,N-dimethylformamide (10.00 mL), followed by successive addition of potassium carbonate (671.70 mg, 4.86 mmol) and 5-methoxypyridin-3-ol (334.47 mg, 2.67 mmol), then stirred at 80 C. for 12 hours. The reaction was quenched by adding 10 mL water and then extracted with ethyl acetate (20.00 mL*3). The organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by column chromatography (silica, petroleum ether/ethyl acetate=10/1 to 2/1) to give 3-(2-((3R,4aR,6aS,7R,10 bR)-3-cyclopentyl-6a,10b-dimethyl-8-dihydromethylene decahydro-1H-naphtho[2,1-d][1,3]dioxin-7-yl)ethoxy)-5-methoxypyridine 442 (700 mg, yield: 63.37%). MS m/z (ESI): 456.6[M+1] 1H NMR (400 MHz, CDCl3) 7.91 (d, J=8 Hz, 2H), 6.69 (t, J=4.4 Hz, 1H), 4.89 (s, 1H), 4.59 (t, J=6 Hz, 2H), 4.08-4.02 (m, 2H), 3.84 (s, 4H), 3.51-3.43 (m, 2H), 2.44-2.40 (m, 2H), 2.05-2.01 (m, 3H), 1.88-1.83 (m, 4H), 1.60 (s, 3H), 1.55-1.35 (m, 6H), 1.45-1.27 (m, 3H) 1.26-1.21 (m, 3H), 0.79 (s, 3H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,109345-94-0, 5-Methoxypyridin-3-ol, and friends who are interested can also refer to it.

Reference:
Patent; Heilongjiang Zhenbaodao Pharmaceutical Co., Ltd.; MEDSHINE DISCOVERY INC.; HE, Haiying; JIANG, Zhigan; XIA, Jianhua; WANG, Jing; HAN, Lixia; LAN, Lihong; ZHOU, Hui; LAI, Kunmin; CHEN, Shuhui; US2018/346438; (2018); 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. 80194-68-9, name is 3-Chloro-5-(trifluoromethyl)picolinic acid, the common compound, a new synthetic route is introduced below. Quality Control of 3-Chloro-5-(trifluoromethyl)picolinic acid

(1) Add 2 mmol) to a 25 ml three-necked flask3,5-Difluoro-5-(trifluoromethyl)picolinic acid8.0 mmol) pyridine and 5 ml acetonitrile, and the ice bath was cooled down to -5C. Then, 0.51 g (4.43 mmol) of methanesulfonyl chloride was slowly added dropwise to the system using a constant pressure dropping funnel. The mixture was stirred for 10 min after the addition was completed, and the mixture was once injected into the system. 3 mmol) 2-amino-3,5-difluorobenzoic acid was added, and after stirring for 10 min, 9 mmol) of pyridine was slowly added dropwise using a constant pressure dropping funnel. The dropping process should keep the temperature below 0C. Continue stirring after the addition was complete. 15min, then continue to slowly add 4.5mmol of methanesulfonyl chloride with a constant pressure dropping funnel, stir for 1h after dropping is completed, remove the ice salt bath, the reaction temperature slowly rises to room temperature, after 12h reaction, add water and dichloromethane extraction The organic layer was passed through a column (petroleum ether: ethyl acetate = 10: 1) to give the intermediate 6,8-difluoro-2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl) -4H-benzo[d][1,3]oxazin-4-one.

The synthetic route of 80194-68-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Guizhou University; Wu Jian; Xu Fangzhou; Wang Yanyan; Yu Gang; Xue Wei; Shi Jun; (24 pag.)CN107759518; (2018); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 109-04-6, 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 109-04-6, name is 2-Bromopyridine. This compound has unique chemical properties. The synthetic route is as follows.

General procedure: To a flame-dried Schlenk tube equipped with a magnetic stir bar was loaded alkyl bromide (0.15 mmol, 100 mol%, solid), halogenated pyridine (0.30 mmol, 300 mol%, solid), ligand (0.015 mmol, 10 mol%), zinc powder (0.45 mmol, 300 mol%). The tube was capped with a rubber septum and moved to a dry glove box, at which NiBr2 (0.015 mmol, 10 mol%), MgCl2 (0.15 mmol, 100 mol%) and Bu4NBr (0.075 mmol, 50 mol%) were added. Then the tube was moved out of the glove box. Alkyl bromide (0.15 mmol, 100 mol%, liquid), halogenated pyridine (0.30 mmol, 300 mol%, liquid), pyridine (0.15 mmol, 100 mol%) and DMA(1.0 mL) were added via syringe. After the reaction mixture was allowed to stir overnight under N2 atmosphere at 30 C, it was directly loaded onto a silica column without work-up. The residue in the reaction vessel was rinsed with small amount of DCM or eluent. Flash column chromatography provided the product as solid or oil.

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 109-04-6, 2-Bromopyridine.

Reference:
Article; Liu, Huiyan; Liang, Zhuye; Qian, Qun; Lin, Kunhua; Synthetic Communications; vol. 44; 20; (2014); p. 2999 – 3007;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 118650-08-1, Adding some certain compound to certain chemical reactions, such as: 118650-08-1, name is Methyl 2-(5-bromopyridin-3-yl)acetate,molecular formula is C8H8BrNO2, 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 118650-08-1.

(5-Bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 58 mg, 0.25 mmol), palladium acetate (3.8 mg, 0.017 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (14 mg, 0.034 mmol), potassium phosphate (108 mg, 0.51 mmol) and water (0.4 mL) were added to a solution of 2-(4-{1-ethyl-1-[3-methyl-4-(4-trimethylsilanyloxy-tetrahydro-thiopyran-4-ylethynyl)-phenyl]-propyl}-2-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Example 136-(4); 100 mg, 0.17 mmol) in toluene (4 mL). The mixture was stirred in a nitrogen stream at 110C for two hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 1:3) to give the title compound (82 mg, 79%). 1H-NMR (chloroform-d): 0.23 (s, 9H), 0.65 (t, 6H, J=7.3Hz), 1.96-2.06 (m, 2H), 2.12 (q, 4H, J=7.3Hz) 2.16-2.24 (m, 2H), 2.24 (s, 3H), 2.41 (s, 3H), 2.7-2.8 (m, 2H), 2.8-2.9 (m, 2H), 3.67 (s, 2H), 3.72 (s, 3H), 6.96-7.12 (m, 5H), 7.30 (d, 1H, J=8.0Hz), 7.60-7.64 (m, 1H), 8.47 (d, 1H, J=1.8Hz), 8.52 (d, 1H, J=1.8Hz).

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. 118650-08-1, Methyl 2-(5-bromopyridin-3-yl)acetate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; CHUGAI SEIYAKU KABUSHIKI KAISHA; EP1894911; (2008); A1;,
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.

To a mixture of tert-butyl 8-bromo-5-methyl-3,4-dihydro-lH-pyrido[4,3-delta]indole- 2(5H)-carboxylate (0.48 g, 1.3 mmol), 4-(benzyloxy)pyridin-2(lH)-one (264 mg, 1.31 mmol), 8-hydroxyquinoline (29 mg, 0.20 mmol), K2CO3 (217 mg, 1.57 mmol) and CuI (38 Attorney’s Docket 2882.023B mg, 0.20 mmol) was added DMSO (5 mL). The reaction mixture was degassed and backfilled with N2. The reaction mixture was heated to 130 0C and stirred at 130 0C overnight. After it was cooled, the mixture was filtered through a layer of Celite. The filtrate was diluted with CH2Cl2, washed with H2O and 5% LiCl, dried with Na2SO4, filtered, and concentrated. Purification by flash column chromatography (silica gel, 5% CH3OH in CH2Cl2) gave the title compound (0.28 g, 44%) as a yellow solid: 1H NMR (500 MHz, CDCl3) delta 7.36-7.29 (m, 8H), 7.13 (d, J= 8.0 Hz, IH), 6.09 (d, J= 2.0 Hz, IH), 6.03 (dd, J = 7.5, 2.0 Hz, IH), 5.05 (s, 2H), 4.61 (s, 2H), 3.84 (m, 2H), 3.66 (s, 3H), 2.82 (m, 2H), 1.49 (s, 9H); ESI MS m/z 486 [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.; WO2009/89482; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 58530-53-3, 2,4-Dibromopyridine, 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, HPLC of Formula: C5H3Br2N, blongs to pyridine-derivatives compound. HPLC of Formula: C5H3Br2N

Step 1: ethyl 2-[(4-bromopyridin-2-yl)amino]-1,3-oxazole-5-carboxylate To a mixture of 2-amino-oxazole-5-carboxylic acid ethyl ester (0.483 g, 3.09 mmol), tris(dba)dipalladium (O) (0.070 g, 0.077 mmol), xantphos (0.120 g, 0.208 mmol) and cesium carbonate (1.95 g, 5.98 mmol) in 1,4-dioxane (15.0 mL, 192 mmol) was added 2,4-dibromopyridine (1.078 g, 4.55 mmol). The reaction was heated in the microwave at 115 C. for 1 h. The reaction was diluted with DCM (30 mL), silica gel was added to the mixture (11 g) and the solvents were removed to absorb material onto the silica. Purification of sample by column chromatography to afford ethyl 2-[(4-bromopyridin-2-yl)amino]-1,3-oxazole-5-carboxylate (0.561 g, 58%). 1H NMR (400 MHz, DMSO-d6) delta 11.64 (s, 1H), 8.34 (s, 1H), 8.21 (d, J=5.3 Hz, 1H), 7.90 (s, 1H), 7.32 (dd, J=5.3, 1.6 Hz, 1H), 4.29 (q, J=7.1 Hz, 2H), 1.29 (t, J=7.1 Hz, 3H) and ethyl 2-[(2-bromopyridin-4-yl)amino]-1,3-oxazole-5-carboxylate (0.13 g, 14%). 1H NMR (400 MHz, DMSO-d6) delta 11.63 (s, 1H), 8.23 (d, J=5.7 Hz, 1H), 8.01-7.84 (m, 2H), 7.47 (dd, J=5.7, 2.0 Hz, 1H), 4.29 (q, J=7.1 Hz, 2H), 1.29 (t, J=7.1 Hz, 3H).

The synthetic route of 58530-53-3 has been constantly updated, and we look forward to future research findings.

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.; Wong, Tzu-Tshin; Xu, He; Xu, Tianlin; Ye, Yingchun; US2015/225422; (2015); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 6443-85-2, 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.6443-85-2, name is 2-(Pyridin-3-yl)acetonitrile, molecular formula is C7H6N2, molecular weight is 118.14, as common compound, the synthetic route is as follows.

Example 1A trans-2-(3-Pyridyl)-3-(3,5-dichlorophenyl)-2-propenenitrile To a stirred solution of 400 g (2.3 mole) 3,5-dichlorobenzaldehyde in 11.4 liters absolute ethanol were added 283.5 g (2.4 mole) 3-pyridylacetonitrile and 720.9 g of K2 CO3. Within 2 minutes of the K2 CO3 addition, a solid precipitate formed. The reaction mixture was stirred about 2.5 hours. Water (22.9 liters) was added to the stirred reaction mixture. After stirring for 1 hour, the mixture was filtered and the filter cake was washed with water (10 liters), dried and recrystallized from isopropanol. Five hundred thirty four g (85% yield) of trans-2-(3-pyridyl)-3-(3,5-dichlorophenyl)-2-propenenitrile were obtained, m.p. 150-151 C.

The chemical industry reduces the impact on the environment during synthesis 6443-85-2, I believe this compound will play a more active role in future production and life.

Reference:
Patent; Rhone-Poulenc Rorer International (Holdings) Inc.; US5418245; (1995); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 5470-70-2, 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 5470-70-2 as follows.

NBS (13.0 g, 0.0728 mol) and BPO (1.6 g, 0.0066 mol) were added to a solution of methyl 6-methylnicotinate (10 g, 0.0662 moles) in CCl4 (100 ml) at room temperature TheThe reaction mixture was heated to 75 & lt; 0 & gt; C and stirred for 12 hours. After cooling, water (80 ml) was added,And extracted with ethyl acetate (200 ml x 2). The organic layer was sequentially saturated with sodium thiosulfate (80 ml)Aqueous solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column (eluent: petroleum ether / ethyl acetate = 20/1) to give methyl 6- (bromomethyl) nicotinate (5.2 g, yield 34%) as a brown solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,5470-70-2, its application will become more common.

Reference:
Patent; CHIA TAI TIANQING PHARMACEUTICAL GROUP CO., LTD.; DING, ZHAO ZHONG; WU, HAO; SUN, FEI; WU, LI FANG; YANG, LING; (97 pag.)TWI558709; (2016); B;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 24484-93-3, 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. 24484-93-3, name is Methyl 4-chloropicolinate. A new synthetic method of this compound is introduced below.

[0136] Into a three-necked bottom flask with tetrahydrofuran (250 mL), methyl 4-chloro-2-picolinate (50 g, 291 mmol, 1 eq) was added. N-(methyl-d3)amine hydrochloride (31 g, 437 mmol, 1.5 eq), anhydrous potassium carbonate (80 g, 583 mmol, 2 eq) were added with stirring. After the mixture was stirred at room temperature for 20 h, water (250 mL) and methyl tert-butyl ether (150 mL) were added. The mixture was stirred and separated to obtain the organic phase. The aqueous layer was extracted with methyl tert-butyl ether (100 mL). The organic phases were combined, dried over anhydrous sodium sulfate and filtered. The solvent in the filtrate was removed under reduced pressure to give the title compound (48 g, purity 99%, yield 96%) as a light yellow oily liquid. [0137] 1H NMR (DMSO-d6, 400 MHz): delta7.64 (dd, J=2 Hz, 5.2 Hz, 1H), 7.97 (d, J=1.6 Hz, 1H), 8.54 (d, J=5.2 Hz, 1H), 8.74 (br, 1H). [0138] MS (ESI, m/z) calcd. for C7H4D3ClN2O: 173, found: 174 [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,24484-93-3, its application will become more common.

Reference:
Patent; SUZHOU ZELGEN BIOPHARMACEUTICAL CO., LTD; Feng, Weidong; Gao, Xiaoyong; Dai, Xiaojun; US2013/60043; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 74115-13-2, 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. 74115-13-2, name is 5-Bromo-3-pyridinol, molecular formula is C5H4BrNO, 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.

Preparation of intermediate 3-(benzyloxy)-5-bromopyridine (LV) is depicted below in Scheme 11. Step 1 (0839) To a solution of 5-bromopyridin-3-ol (L) (174 mg, 1.0 mmol) in DMF (3 mL) was added potassium carbonate (415 mg, 3.0 mmol). The slurry was heated at 90 C. for 1 hour and then cooled to 25 C. The (bromomethyl)benzene (LIV) (171 mg, 1.0 mmol) was added and the mixture was stirred at 25 C. overnight. The reaction was worked-up using a saturated sodium bicarbonate and ethyl acetate extraction. The product was purified by ISCO column eluted with 40-100% EtOAc-Hexanes. The 3-(benzyloxy)-5-bromopyridine (LV) (105 mg, 0.398 mmol, 39.8% yield) was obtained as yellow oil. MS: 266.1. ESIMS found for C12H10BrNO m/z 266.1 (M+H).

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 74115-13-2, 5-Bromo-3-pyridinol.

Reference:
Patent; Samumed, LLC; KC, Sunil Kumar; Wallace, David Mark; Cao, Jianguo; Chiruta, Chandramouli; Hood, John; (264 pag.)US2016/68551; (2016); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem