Day: June 7, 2021

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.1597-33-7, name is 2-Fluoropyridin-3-amine, molecular formula is C5H5FN2, molecular weight is 112.11, as common compound, the synthetic route is as follows.SDS of cas: 1597-33-7

To a solution of the corresponding amines (1 equiv.) in dichloromethane was added pyridine (1 equiv.) and phenyl chloroformate (1 equiv.) at 0 C. Stirring was continued for 2 h followed by the addition of the scaffold amine (1 equiv.) and DMAP (0.2 equiv.). The reaction mixture was refluxed overnight. After cooling, water was added and extracted with dichloromethane. The pooled organic fractions were brine washed, dried, concentrated and purified by Reverse Phase Prep-HPLC to provide compounds A6.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1597-33-7, 2-Fluoropyridin-3-amine, and friends who are interested can also refer to it.

Reference:
Patent; AGIOS PHARMACEUTICALS, INC.; POPOVICI-MULLER, Janeta; SALITURO, Francesco Gerald; SAUNDERS, Jeffrey Owen; TRAVINS, Jeremy; YAN, Shunqi; WO2014/62511; (2014); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 14150-94-8, Adding some certain compound to certain chemical reactions, such as: 14150-94-8, name is 1-Methyl-3,5-dinitro-1H-pyridin-2-one,molecular formula is C6H5N3O5, 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 14150-94-8.

A mixture ofbenzyl (3-oxocyclohexyl)carbamate (247 mg, 0.999 mmol) and 1-methyl- 3,5-dinitropyridin-2(1H)-one (300 mg, 1.507 mmol) in ammonia/MeOH (1M, 6 mL) was microwaved at 90 C for 30 mm to provide a blackish-red solution. Eleven more samples of the same composition were run under the same conditions. The twelve samples were combined and evaporated under reduced pressure. The residue was partitioned between DCM (300 mL) and saturated aqueous NaHCO3 (100 mL). The organic layer was washed with brine (100 mL), dried (MgSO4), filtered, treated with silica gel, and evaporated under reduced pressure. Purification by silica gel chromatography (0 to 50% EtOAc in hexanes) provided a mixture of benzyl (3-nitro- 5,6,7, 8-tetrahydroquinolin-7-yl)carbamate and undesired regioi somer benzyl (3 -nitro-5 ,6,7, 8-tetrahydroquinolin-5-yl)carbamate as a pale yellow gum. The mixture was used without further purification. MS (ESI, m/z): 213 [M+H]t; j00424J A solution of benzyl (3 -nitro-5 ,6,7, 8-tetrahydroquinolin-7-yl)carbamate and regioisomer (2.64 g, 8.07 mmol) in ethanol (110 mL) was treated with tin(II) chloride dihydrate (9.10 g, 40.3 mmol) and conc. HC1 (1 mL), then stirred at 80 C for 75 mm. The solution was allowed to cool, then was concentrated under reduced pressure to about 15 mL. The sample was made basic (pH 9) by addition of saturated aqueous NaHCO3; about midway through, the sample was diluted with DCM (100 mL). The mixture was triturated, then filtered, and the filter cake was washed with DCM (50 mL). The filter cake was triturated and sonicated in MeOH (200 mL), then the mixture was filtered. The slightly cloudy filtrate was filtered through Celite 545, then concentrated to provide a yellow solid. Purification by silica gel chromatography (0 to 15% MeOH in DCM) provided a mixture of benzyl (3-amino-5,6,7,8-tetrahydroquinolin-7-yl)carbamate and regioisomer as a yellow solid. The mixture was used without further purification. MS (ESI, m/z):298 [M+H]t; 1004251 A sample of benzyl (3-amino-S ,6, 7, 8-tetrahydroquinolin-7-yl)carbamate and regioisomer (1.25 g, 4.22 mmol) was treated with ACN (17 mL). The material was cooled on a dry ice / ethylene glycol bath (approximately -10 to -15 C) and PTSA monohydrate (1.61 g, 8.45 mmol) was added. After stirring 10 mm, a solution of potassium iodide (1.05 g, 6.33 mmol) and sodium nitrite (0.436 g, 6.32 mmol) in water (3.4 mL) was added dropwise over 20 mm. The dry ice bath was replaced with an ice bath, and the reddish-brown mixture was stirred at 0 C for 3 h 40 mm. The solution was diluted with EtOAc (50 mL), cooled on an ice bath and treated with saturated aqueous NaHCO3 until basic (pH 8-9). The organic layer was removed and the aqueous layer was extracted once more with EtOAc (50 mL). The combined organics were washed sequentially with water and brine (50 mL each), dried (Na2504), filtered, treated with silica gel, and evaporated under reduced pressure. Purification by silica gel chromatography (0 to 23% EtOAc in hexanes) provided a mixture of benzyl (3-iodo-S,6,7,8-tetrahydroquinolin-7- yl)carbamate and regioisomer as a yellow solid. The mixture was used without further purification.MS (ESI, m/z): 409 [M+H]; 1004261 A mixture of t-BuXPhos Pd G4 (76.3 mg, 94.4 tmole), benzyl (3-iodo-5,6,7,8- tetrahydroquinolin-7-yl)carbamate and regioisomer (605.0 mg, 1.482 mmol), tert-butyl piperazine-1-carboxylate (553.5 mg, 2.97 mmol), and sodium tert-butoxide (257.1 mg, 2.68 mmol) was sealed in a 40-mL vial. The atmosphere was evacuated and replaced with nitrogen, three times. Dioxane (15 mL) was added and the solution was stirred at ambient temperature for three days. Material at the same stage from a previous run (from 40.7 mg, 0.100 mmol iodo starting material) was added. The mixture was diluted with EtOAc (100 mL), treated with silica gel, and evaporated under reduced pressure. Purification by silica gel chromatography (0 to 87% EtOAc in hexanes) provided a mixture of tert-butyl 4-(7-(((benzyloxy)carbonyl)amino)-5 ,6,7, 8-tetrahydroquinolin-3 – yl)piperazine-1-carboxylate and regioisomer as a yellow foam. The mixture was used without further purification. MS (ESI, m/z): 467 [M+H].

According to the analysis of related databases, 14150-94-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; FORMA THERAPEUTICS, INC.; ZABLOCKI, Mary-Margaret; GUERIN, David J.; NG, Pui Yee; WANG, Zhongguo; SHELEKHIN, Tatiana; CARAVELLA, Justin; LI, Hongbin; IOANNIDIS, Stephanos; (518 pag.)WO2019/32863; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 82671-06-5, 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 82671-06-5 as follows.

Example 16A (^-Sjdelta-Difluoro^-hydroxy^^i^Kfl.SloxathioIoS^-clpyridin-theta- ylmethyl)amino]-l-piperidinyl}methyI)-4,5-dihydro-7H-pyrrolo[3,2,l-^]-l?5- naphthyridin-7-one dihydrochloride(a) 2-Chloro-5-fluoro-6-(methyloxy)-3-pyridinecarboxylic acidA solution of 2,6-dichloro-5-fluoro-3-pyridinecarboxylic acid (51.12g, 243 mmol) in methanol (400 ml) was treated with sodium methoxide in methanol (25% w/v, 100 ml, 535 mmol) and the mixture heated to reflux for 4 hours. The cooled mixture was treated with water (400 ml) and acidified to pH2 with aqueous hydrochloric acid (2M) then concentrated to ca 400 ml. Filtration, washing with water and drying in vacuo over P2O5 for 18h afforded the product as a white solid (32.65g, 65%). MS (+ve ion electrospray) m/z 208 (MH+).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,82671-06-5, its application will become more common.

Reference:
Patent; GLAXO GROUP LIMITED; WO2007/71936; (2007); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 18653-75-3, 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 18653-75-3, name is 2-(1H-Imidazol-2-yl)pyridine. This compound has unique chemical properties. The synthetic route is as follows.

Na2MoO4·2H2O (0.847g, 3.5mmol), 2-pyim (0.0065g, 0.040mmol), Mo powder (0.06g, 0.60mmol), ZnCl2 (0.136g, 1mmol), H3PO3 (0.02g, 0.25mmol), tetrabutylammonium hydroxide (TBAOH, 0.2mL, 0.3mmol) and distilled water (9.0mL) were stirred for 1h under the room temperature. An aqueous solution of 2molL-1 HCl was added into the mixture and the pH value was adjusted to 3.8. After that, the mixture continues to stir for an another 2h. Finally, the product was transferred to 25 Teflon-lined antoclave and was heated to 180C for 3days before cooled down to the room temperature. In the end, dark-red crystals 2 were collected and dried in air (yield: 62.45%). Elemental analysis: calculated: C, 14.11; H, 1.36; N, 6.17; found: C, 14.01; H, 1.28; N, 6.58.

According to the analysis of related databases, 18653-75-3, the application of this compound in the production field has become more and more popular.

Reference:
Article; Han, Ye-Min; Cheng, Wei-Wei; Cao, Jia-Peng; Yang, Mu-Xiu; Hong, Ya-Lin; Kang, Run-Kun; Xu, Yan; Inorganica Chimica Acta; vol. 498; (2019);,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 850349-02-9, 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.850349-02-9, name is 8-Bromoimidazo[1,2-a]pyridine, molecular formula is C7H5BrN2, molecular weight is 197.03, as common compound, the synthetic route is as follows.

l-Iodo-2,5-pyrrolidinedione (2.28 g, 10.15 mmol) was added to a solution of 8-bromo- imidazo[l,2-a]pyridine (2 g, 10.15 mmol) in CH3CN (8 ml). The r.m. was stirred at r.t. for 30 min. The mixture was concentrated in vacuo and the residue was purified by flash chromatography over silicagel (eluent: DCM/MeOH(NH3) from 100/0 to 99/1). The product fractions were collected and the solvent was evaporated in vacuo. Yield: 2.89 g of intermediate 5 (84.6 %).

Statistics shows that 850349-02-9 is playing an increasingly important role. we look forward to future research findings about 8-Bromoimidazo[1,2-a]pyridine.

Reference:
Patent; ORTHO-MCNEIL-JANSSEN PHARMACEUTICALS, INC; GIJSEN, Henricus, Jacobus, Maria; MACDONALD, Gregor, James; BISCHOFF, Francois, Paul; TRESADERN, Gary, John; TRABANCO-SUAREZ, Andres, Avelino; VAN BRANDT, Sven, Franciscus, Anna; BERTHELOT, Didier, Jean-Claude; WO2010/70008; (2010); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 286947-03-3, 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.286947-03-3, name is 5-Bromo-2-chloro-3-methoxypyridine, molecular formula is C6H5BrClNO, molecular weight is 222.47, as common compound, the synthetic route is as follows.

c. Preparation of Compound To a 25 mL flask containing (63.8 mg, 1.2 mmol) of sodium ethoxide was added 3 mL dry ethanol. The mixture was stirred for 30 minutes. 2-Chloro-3-methoxy-5-bromopyridine (230 mg, 1.04 mmol) was added to the mixture and heated to 60 C for 16 hours. The reaction was allowed to cool and the solvent was removed. Ethyl acetate was added (50 ml) was added to the residue. The ethyl acetate solution was washed with water and then brine. The organic solvent was dried and concentrated, purified by ISCO flash chromatography using 10% ethyl acetate in hexane to give 220 mg (97% yield) of the desired product. NMR (300 MHz, CDC13) delta: 7.71 (s, IH), 7.09 (s, IH), 4.37 (qt, 2H), 3.82 (s, 3H), 1.38 (t, 3H).

The chemical industry reduces the impact on the environment during synthesis 286947-03-3, I believe this compound will play a more active role in future production and life.

Reference:
Patent; RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY; LAVOIE, Edmond J.; BAUMAN, Joseph David; PARHI, Ajit; SAGONG, Hye Yeon; PATEL, Disha; ARNOLD, Eddy; DAS, Kalyan; VIJAYAN, Suyambu Kesava; WO2014/43252; (2014); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 1072-97-5, 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 1072-97-5 as follows.

Step-1: Synthesis of ethyl 6-bromoimidazo[1,2-a]pyridine-2-carboxylate To a stirred solution of 5-bromopyridin-2-amine (10.0 g, 56.0 mmol, 1.0 eq.) and ethyl 3-bromo-2-oxopropanoate (12.6 g, 64.0 mmol, 1.1 eq.) in Dioxane (200 mL) was added MgSO4 (20.0 g, 150.0 mmol, 3.0 eq.) at RT. The resulting mixture heated to 80 C. for 16 h. Following this, reaction mixture cooled to RT filtered the solid and under vacuum and filtrate concentrated to get crude. The crude purified by normal phase silica-gel column to get title compound (12 g, 79%). LCMS: 269.9 [M+1]+; 1H NMR (400 MHz, DMSO-d6) delta ppm 8.91 (d, J=1.32 Hz, 1H) 8.47 (s, 1H) 7.62 (d, J=9.65 Hz, 1H) 7.47 (dd, J=9.65, 1.75 Hz, 1H) 4.31 (q, J=7.16 Hz, 2H) 1.31 (t, J=7.02 Hz, 3H)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1072-97-5, its application will become more common.

Reference:
Patent; INTEGRAL BIOSCIENCES PRIVATE LIMITED; CHAKRAVARTY, Sarvajit; PENDHARKAR, Dhananjay; RAMACHANDRAN, Sreekanth A.; BATHULA, Chandramohan; SONI, Sanjeev; KUMAR, Vivek; SAEED, Uzma; DANODIA, Abhinandan Kumar; SHARMA, Ankesh; JADHAVAR, Pradeep S.; US2020/206233; (2020); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 1603-40-3, 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 1603-40-3, name is 3-Methylpyridin-2-amine. This compound has unique chemical properties. The synthetic route is as follows.

Example 1; Synthesis of 3-amino-1-hydroxy-3,4-dihydro-1,8-naphthyridin-2(1H)-one, trifluoroacetate salt (8); 3-Methyl-2-nitropyridine (2); To a solution of H2O2 (120 g, 1.1 mol) in fuming sulfuric acid (250 mL) was added a solution of 3-methylpyridin-2-amine (1) (16 g, 0.15 mol) in concentrated sulfuric acid (50 mL) drop-wise, while keeping the reaction temperature at 0 C. After stirring for 3 h at 10-25 C., the reaction mixture was brought to pH=11-12 by adding an aqueous 40% NaOH solution at 0-5 C. The resulting mixture was extracted with ethyl acetate (3×500 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over Na2SO4 and filtered. The solvent was removed in vacuo to give the desired compound (18.2 g, 89%) as a yellow oil.

According to the analysis of related databases, 1603-40-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Pfizer Inc; US2010/324043; (2010); 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. 136117-74-3, name is Imidazo[1,2-a]pyridine-8-carbaldehyde, the common compound, a new synthetic route is introduced below. COA of Formula: C8H6N2O

Preparation of ethyl imidazopyridine propenoate (According to the Literature Method: Chezal, J. M. and al. J. Org. Chem. 2001, 66, 6576-6584).Ethyl azidoacetate (1.81 g, 14.0 mmol) was added dropwise at -30 C. to a stirred solution containing sodium (0.20 g, 8.70 mmol) in dry ethanol (10 mL). To this solution was added dropwise a solution of aldehyde 4 (1.00 mmol) in dry ethanol (8 mL). The reaction mixture was returned back room temperature and stirred for 3 h (CAUTION: an exothermic reaction can take place, with gas expansion). The solution was poured into aqueous saturated ammonium chloride solution (30 mL) and then extracted with CH2Cl2. The organic layers were dried (Na2SO4), filtered and evaporated in vacuo. The crude product was purified by chromatography using CH2Cl2 as eluent to afford the azide derivative 6; Example 35 Ethyl alpha-azido-beta-(imidazo[1,2-a]pyridin-8-yl)propenoate (6a) From 4a (yield: 10%); mp: 150-152 C.; IR (KBr) 2100, 1700, 1600, 1280 cm-1; 1H NMR (400 MHz, CDCl3) delta 1.41 (t, 3H, J=7 Hz), 4.39 (q, 2H, J=7 Hz), 6.83 (t, 1H, J=7 Hz), 7.57 (d, 1H, J=1 Hz), 7.61 (d, 1H, J=1 Hz), 7.76 (s, 1H), 8.06 (dd, 1H, J=7, 1 Hz), 8.17 (dd, 1H, J=7, 1 Hz). MS m/z 257 (M+, 1), 229 (61), 183 (100), 155 (31), 129 (23), 104 (14). Further elution gave 8-methylimidazo[1,2-a]pyridine (yield: 10%-Kaiser, C. and al. J. Med. Chem. 1992, 35, 4415-4424).

The synthetic route of 136117-74-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Universite D’Auvergne Clermont 1; Universite Francois Rabelais Tours; Katholieke Universiteit Leuven; US2010/93781; (2010); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 59281-14-0, 5-(Benzyloxy)-2-(hydroxymethyl)pyridin-4(1H)-one, 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, Computed Properties of C13H13NO3, blongs to pyridine-derivatives compound. Computed Properties of C13H13NO3

To a stirred solution of compound 9b (2.7g) in NaOH solution (0.567g in 55 mL of water) was added 10%Pd-C(l .4g) portion wise under nitrogen atmosphere. The nitrogen was replaced with hydrogen and stirred at RT for 16h. The reaction mass was filtered under celite and concentrated under reduced pressure to give 2.2 g of the required compound as a mixture. Proceeded with crude to the next step.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,59281-14-0, 5-(Benzyloxy)-2-(hydroxymethyl)pyridin-4(1H)-one, and friends who are interested can also refer to it.

Reference:
Patent; VITAS PHARMA RESEARCH PVT LTD; ALAPATI, Chandrasekhar; BANERJEE, Ankita; RANGARAJAN, Radha; KUMAR, Rajinder; WO2014/57415; (2014); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem