Day: August 13, 2021

Electric Literature of 524955-09-7, 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. 524955-09-7, name is 3-Chloro-4-(pyridin-2-ylmethoxy)aniline, molecular formula is C12H11ClN2O, 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.

Following hydrogenation to form the first aniline intermediate, acid catalyzed coupling was performed to prepare 4-[3-chloro-4-(2-pyridylmethoxy)anilino]-3-cyano-7-ethoxy-6-N-acetylaminoquinoline, as shown below: To perform the coupling reaction, the two reactants were heated together in alcohol at 65-78 C. over 4-6 hours, yielding the product. The reaction begins as an amber slurry and thickens to a lighter beige slurry as it approaches completion. Upon scaling up from 75 g to 350 g, it proved necessary to add a catalytic amount (0.025 eq.) of methanesulfonic acid to initiate the reaction. As a specific example, 4-chloro-3-cyano-7-ethoxy-6-N-acetylaminoquinoline (0.141 kg, 0.49 mole) was added to the mixture of Example 2, followed by ethanol (0.037 L) to give a suspension. A catalytic amount of methanesulfonic acid (1.17 g) was added at 20-25 C. The resulting slurry was heated to 70-75 C. and held for a minimum of 4 hours. Thickening of the slurry was evident after 1.5 hours. Following reaction completion, the mixture was cooled to room temperature and may be used ?as is? in the telescoped reaction of Example 4 below.; As solvents EtOH, DMF or other suitable solvent may be used. Experimental results obtained using different solvents and reaction conditions are shown in Table 3. Difficulty filtering the product of this step (noted in several entries on Table 3) was circumvented by not isolating the solid at this point, but telescoping the reaction with the next step. It has been found that on the order of 20 volumes of EtOH were necessary to achieve reasonable stirring, but that the reaction can proceed in only 10 volumes of DMF, without significant loss in purity. In Table 3, where the entry is labelled NI, the intermediate product was not isolated, but carried into the next reaction step. TABLE 3 Coupling Reaction Coupling Temp Time Yield Solvent Solvent ( C.) (h) (%) Comments IPA EtOH 78 4 85.4 contains impurity THF EtOH 78 4 90.5 v. slow filtration THF THF 68 4 NA Only 16% product formed THF EtOH 78 4 94.2 v. slow filtration EtOH IPA 82 5 NA No reaction EtOH MeOH 65 5 60.0 v. slow filtration THF EtOH 78 1.5 80.3 v. slow filtration (MeSO3H) THF EtOH 78 4 86.0 v. slow filtration THF EtOH 78 3 85.7 4 h filtration – hard, green (MeSO3H) coated solid on drying THF Dimethoxy 85 2 74.2 Faster filtration (<1 hr) ethane Nice yellow solid THF Diethoxy 85 5 - - Methane THF Dimethoxy 70 6 - - Ethane THF EtOH 78 6 96.6 Slow filtration THF DMF 78 0.5 65.6 Some product lost in filtrate (MeSO3H) THF DMF 70 8 NI See Note 1 (MeSO3H) THF EtOH 78 6 ND See Note 2 (MeSO3H) THF EtOH 78 4 NI Yield to the free base is (MeSO3H) 80.4%3/ THF EtOH 75 4 NI Yield to the free base is (MeSO3H) 83%3/ THF EtOH 75 4 NI Yield to the free base is (MeSO3H) 86%3/ NR = no reaction, NI = not isolated; ND = not determined; NA = not available 1. Carried through to the deprotection and generation of free base to give 69.5% overall yield. 2. The overall yield after the deprotection and generation of the free base is 76.1% 3This reaction was not filtered at all but taken as slurry to the next step. 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 524955-09-7, 3-Chloro-4-(pyridin-2-ylmethoxy)aniline. Reference:
Patent; WYETH; US2006/270668; (2006); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 65753-47-1, Adding some certain compound to certain chemical reactions, such as: 65753-47-1, name is 2-Chloro-3-(trifluoromethyl)pyridine,molecular formula is C6H3ClF3N, 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 65753-47-1.

2-Chloro-3-trifluoromethyl-pyridine (3 g, 16.53 mmol) was dissolved in 30ml of a solution of sodium methoxide (5.4M) in methanol. The mixture was stirred at ambient temperature for 2 days. After this period of time, the reaction was taken into ice and extracted with DCM three times. The combined extract was washed with brine, dried over magnesium sulfate and concentrated in vacuo to give 2-methoxy-3-trifluoromethyl-pyridine as a light liquid (2.7 g, 89% yield). 1 H-NMR (400 MHz, DMSO-d6, 298 K): ? ppm 3.98 (s, 3H) 7.2 (dd, 1 H) 8.1 1 (d, 1 1-1) 8.45 (d, 1 H). MS: 178.1 [M+1 ]+, Rt(1) =1 .29 min.

According to the analysis of related databases, 65753-47-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NOVARTIS AG; FURET, Pascal; HEBACH, Christina; HOeGENAUER, Klemens; HOLLINGWORTH, Gregory; LEWIS, Ian; SMITH, Alexander, Baxter; SOLDERMANN, Nicolas; STAUFFER, Frederic; WOLF, Romain; ZECRI, Frederic; WO2013/57711; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 1211533-83-3, 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. 1211533-83-3, name is 5-Bromo-6-methoxypyridin-2-amine, molecular formula is C6H7BrN2O, 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.

To a solution of 5-bromo-6-methoxypyridin-2-amine (1.0 g, 4.9 mmol) in DCM (20.0 mL) was added 2-methylbenzenesulfonyl chloride (1.1 g, 5.9 mmol, 853.6 uL) and pyridine (1.2 g, 14.8 mmol, 1.2 mL). The mixture was stirred at 45C for 12 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography (S1O2, Petroleum ether / Ethyl acetate = 100/1 to 50/1) to afford N-(5-bromo-6-methoxypyridin- 2-yl)-2-methylbenzenesulfonamide (1.0 g, 2.5 mmol, 52.2% yield). M+H+ = 357.0 (LCMS).

According to the analysis of related databases, 1211533-83-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; QUENTIS THERAPEUTICS, INC.; VACCA, Joseph P.; LI, Dansu; BETTIGOLE, Sarah; (214 pag.)WO2019/94641; (2019); 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. 76093-33-9, name is (R)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid. This compound has unique chemical properties. The synthetic route is as follows. name: (R)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid

EXAMPLE 11 Production of 3-(1-methyl-2-pyridinium)methyl (4S)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-pyridine-3-carboxylate iodide STR21 To a solution of 1 g (3.01 mmol) of (4R)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-pyridine-3-carboxylic acid in 4 ml of THF were added 1.23 g (7.50 mmol) of 2-(chloromethyl)pyridine and 460 mg (3.35 mmol) of potassium carbonate and the mixture was stirred at room temperature for 5 hours. The mixture was diluted with 50 ml of ethyl acetate, washed with water, and hydrated and dried over salt cake. Thereafter, the solvent was distilled off under reduced pressure to obtain 1.13 g of the residue. The residue was passed through a silica gel column for purification to obtain 673 mg of 3-(2-pyridyl)methyl (4S)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-pyridine-3-carboxylate.

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, 76093-33-9, (R)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid.

Reference:
Patent; Mercian Corporation; US6133443; (2000); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 791644-48-9 ,Some common heterocyclic compound, 791644-48-9, molecular formula is C6H2ClFN2, 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.

To a solution of compound 4 (50 g, 321.7 mmol) in 1- butanol (1 L) was added hydrazine monohydrate (150 mL, 3.2 mol) , and the mixture was refluxed for 4 h. The mixture was cooled to room temperature and concentrated. The precipitate was successively washed on filter with water (2x) and Et2<0 (2x) and dried in vacuo overnight to give compound 5 (44 g, 88%) as a yellow solid. 1H NMR (DMSO-d6, 300 MHz): delta 5.53 (s, 2H); 7.94 (dd, IH); 8.35 (dd, IH); 12.02 (s, IH). These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,791644-48-9, its application will become more common. Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2009/18415; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 10386-27-3, 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. 10386-27-3, name is 2-Bromoisonicotinonitrile, molecular formula is C6H3BrN2, 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.

StepD: (4S)-tert-Butyl 4-((l-(2-chlorophenyl)-2-(3,3-difluorocyclobutylamino) -2-oxoethyl){3- fluorophenyl)carbamoyl)-3-(4-cyanopyridin-2-yl)-2-oxoimidazolidine-l-carboxylate. To a 25 mL flask charged with 1,4-dioxane (4.5 mL) were added(4S)-tert-butyl4-((l-(2-chlorophenyI)- 2-(33-difluoro cyclo butylamino)-2-oxoethyl)(3-fiuoro -phenyl)carbamoyl)-2-oxoimidazolidine- 1- carboxylate (250 mg, 0.43 mmol), 2-bromoisonicotinonitrile (122 mg 0.65 mmol), CS2CO3 (281 mg, 0.862 mmol), Xant-Phos (25 mg 0.043 mmol) and Pd2(dba)3 (40 mg, 0.043 mmol). The mixture was degassed and refilled with nitrogen, and then heated to 100 °C for 3 hr. The resulting mixture was cooled and filtered. The filtrate was concentrated in vacuo and the residue was purified by a standard method to give both epimers. The epimers were further separated by a standard method to give the desired product. ‘HNMR (400 MHz, CDC13): delta 8.58 (s, 1H), 8.48 (t, J= 5.9 Hz, 1H), 7.71 (d, J= 8.4 Hz, 1H),7.37 – 7.16 (m, 4H), 7.15 – 6.76 (m, 4H), 6.56 – 6.31 (m, 2H), 4.95 – 4.75 (m, 1H), 4.31 (s, 1H), 3.86 (dd,J= 10.8, 5.1 Hz, 1H), 3.66 (m, 1H), 2.99 (m, 2H),2.61 -2.27 (m, 2H), 1.56 (s,9H).MS : 683(M + 1)+.

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 10386-27-3, 2-Bromoisonicotinonitrile.

Reference:
Patent; AGIOS PHARMACEUTICALS, INC.; LEMIEUX, Rene M.; POPOVICI-MULLER, Janeta; TRAVINS, Jeremy M.; CAI, Zhenwei; CUI, Dawei; ZHOU, Ding; WO2015/10297; (2015); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 63071-10-3, 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. 63071-10-3, name is (4-Chloropyridin-2-yl)methanol, molecular formula is C6H6ClNO, 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.

Example 61 1-(4-(4-(2-(hydroxymethyl)pyridin-4-yl)benzyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide A microwave vial was charged with Intermediate III (60 mg, 0.144 mmol), (4-chloro-2-pyridinyl)methanol (24.77 mg, 0.173 mmol), K3PO4 (92 mg, 0.431 mmol), second generation Xphos Precatalyst (11.31 mg, 0.014 mmol), water (0.5 mL), THF (2 mL), and was evacuated and degassed with N2 for 5 min. The mixture was heated in the microwave at 100 C. for 2 hr, cooled to RT, and concentrated in vacuo. The resulting crude product was purified by FCC (gradient 2%-10% MeOH in DCM) then by preparative HPLC to afford 1-(4-(4-(2-(hydroxymethyl)pyridin-4-yl)benzyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (2 mg, 3%): LCMS Rt=1.23 min (condition A), MS (M+1)=399.4. 1H NMR (400 MHz, Methanol-d4) delta 8.48 (dd, J=5.3, 0.8 Hz, 1H), 7.82 (dd, J=1.8, 0.9 Hz, 1H), 7.78-7.66 (m, 2H), 7.57 (dd, J=5.3, 1.9 Hz, 1H), 7.51-7.30 (m, 6H), 6.68 (d, J=0.9 Hz, 1H), 4.75 (s, 2H), 4.14 (s, 2H), 2.33 (d, J=0.7 Hz, 3H).

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 63071-10-3, (4-Chloropyridin-2-yl)methanol.

Reference:
Patent; NOVARTIS AG; DALES, Natalie; GORMISKY, Paul; KERRIGAN, John Ryan; SHU, Lei; (159 pag.)US2019/77773; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 80194-69-0, 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 80194-69-0, name is 5-(Trifluoromethyl)picolinic acid. This compound has unique chemical properties. The synthetic route is as follows.

A mixture of (1S, 4S)-2-{(15)-1-[4-(allyloxy)-2,3-dimethylphenyl]ethyl}-2,5-diazabicyclo-[2.2.1]heptane (7.3 g, 25.5 mmol), 5-(trifluoromethyl)pyridine-2-carboxylic acid (4.97 g, 26.0 mmol), BOP (16.9 g, 38.3 mmol) and NEt3 (8.89 mL, 63.8 mmol) in N,N-dimethylacetamide (50 mL) is heated at 40 C. under N2 overnight. The reaction mixture is cooled to room temperature, diluted with 1N NaOH (100 mL), and extracted with EtOAc. The organic layer is isolated, washed with 1N NaOH, water and brine, dried over Na2SO4, and concentrated under reduced pressure. The residue is purified by silica gel chromatography with EtOAc as the eluent to afford the title compound as a brown oil. 1HNMR (400 MHz, CDCl3) delta: 8.86 (s, 0.67H), 8.83 (s, 0.33H), 8.02-8.13 (m, 2H), 7.28 (m, 1H), 6.72 (m, 1H), 6.07 (m, 1H), 5.43 (m, 1H), 5.26 (m, 1H), 4.97 (s, 1H), 4.49-4.53 (m, 2H), 3.72-4.00 (m, 2H), 3.52 (m, 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.83 (d, 0.67H), 2.78 (d, 0.33H), 2.33 (s, 2H), 2.25 (s, 1H), 2.21 (s, 2H), 2.19 (s, 1H), 1.95 (m, 1H), 1.72 (m, 1H), 1.25-1.31 (m, 31). LC-MS m/z (M+H): 460.

According to the analysis of related databases, 80194-69-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Hutchinson, Alan J.; Chenard, Bertrand L.; Li, Guiying; Ghosh, Manuka; Tarrant, James G.; Yoon, Taeyoung; Luke, George P.; Lee, Kyungae; O’Donnell, Mary-Margaret E.; Pringle, Wallace C.; Peterson, John M.; Hodgetts, Kevin J.; Steenstra, Cheryl K.; Doller, Dario; US2006/9456; (2006); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 63897-12-1, 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. 63897-12-1, name is 2,4-Dichloro-6-methyl-3-nitropyridine. A new synthetic method of this compound is introduced below.

EXAMPLE 3 3-Amino-2,4-bis(methylthio)-6-methylpyridine To a solution of 15.5 g (0.22 mol) sodium methanethiolate in 200 ml methanol was added slowly with stirring under nitrogen a solution of 20.8 g (0.1 mol) 3-nitro-2,4-dichloro-6-methylpyridine in 150 ml methanol. A precipitate formed and the mixture was stirred overnight at room temperature. The mixture was then filtered and the solid was washed first with methanol and then with water. 3-Nitro-2,4-bis(methylthio)-6-methylpyridine (18.9 g, 82% yield) was obtained as a yellow solid, mp 172-176C. 1 H NMR (CDCl3): delta2.45 (s, 3H); 2.51 (s, 3H); 2.55 (s, 3H); 6.77 (s, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,63897-12-1, its application will become more common.

Reference:
Patent; Pfizer Inc.; US5596001; (1997); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 10366-35-5, 2-Chloronicotinamide, 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: C6H5ClN2O, blongs to pyridine-derivatives compound. HPLC of Formula: C6H5ClN2O

General procedure: To a solution of the corresponding amide (2 mmol) in THF (10 mL) was added chlorocarbonylsulfenyl chloride (350 muL, 4 mmol). The mixture was stirred at ambient temperature for 16 h. The solvent was removed in vacuo and the crude products were puried by silica-gel column chromatography using ethyl acetate/hexane as eluent solvent system.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,10366-35-5, 2-Chloronicotinamide, and friends who are interested can also refer to it.

Reference:
Article; Yang, Jianzhong; Pi, Weiyi; Xiong, Li; Ang, Wei; Yang, Tao; He, Jun; Liu, Yuanyuan; Chang, Ying; Ye, Weiwei; Wang, Zhenling; Luo, Youfu; Wei, Yuquan; Bioorganic and Medicinal Chemistry Letters; vol. 23; 5; (2013); p. 1424 – 1427;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem