Category: pyridine-derivatives

Reference of 902837-39-2, 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.902837-39-2, name is 3-Bromo-5-iodopyridin-4-amine, molecular formula is C5H4BrIN2, molecular weight is 298.91, as common compound, the synthetic route is as follows.

8-Bromo-4-methyl-1,6-naphthyridin-2(1H)-one To a solution of 3-Bromo-5-iodopyridin-4-amine (1.5 g, 5.02 mmol) in DMF (12 mL) was added methyl crotonate (1.064 mL, 10.04 mmol), triethylamine (0.974 mL, 7.03 mmol), tri-o-tolylphosphine (0.12 g, 0.401 mmol) and palladium(II)acetate (0.045 g, 0.201 mmol) under nitrogen and the mixture was stirred at 120 C. for 48 h. The DMF was evaporated (V10 biotage system) and the resulting residue was purified by chromatography on silica gel (biotage, CH2Cl2/MeOH, 100:0 to 92:8) to give the product (0.82 g, 69%) as a red solid. This solid was further purified by recrystallization from hot EtOAc to give the pure product (503 mg, 42%) as a beige solid.

Statistics shows that 902837-39-2 is playing an increasingly important role. we look forward to future research findings about 3-Bromo-5-iodopyridin-4-amine.

Reference:
Patent; Merck Patent GmbH; Cancer Research Technology, Ltd.; SCHIEMANN, Kai; BLAGG, Julian; MALLINGER, Aurelie; RINK, Christian; SEJBERG, Jimmy; HONEY, Mark; (139 pag.)US2016/16951; (2016); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 1227594-89-9 ,Some common heterocyclic compound, 1227594-89-9, molecular formula is C6H3F4NO, 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.

[00542] Step C: tert-butyl ethyl(1-((1r,4r)-4-hydroxycyclohexyl)-3-(oxazol-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)carbamate (30 mg, 0.07 mmol) was dissolved in THF (0.5 mL). 6-hydroxy-2-methylpyridazin-3(2H)-one (26 mg, 0.21 mmol) and PPh3 (55 mg, 0.21 mmol) were added, followed by DIAD (0.041 mL, 0.21 mmol). The reaction mixture was stirred overnight and then concentrated. The residue was dissolved in DCM (1 mL) and 4N HCl in dioxane (1 mL) was added and stirred for 2 h. The reaction mixture was concentrated and the residue purified on C-18 silica column (5 to 95% ACN in water with 0.1% TFA) to afford N-ethyl-1-((1s,4s)-4-((3-fluoro-4-(trifluoromethyl)pyridin-2-yl)oxy)cyclohexyl)-3-(oxazol-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-amine bis(2,2,2-trifluoroacetate) (17.2 mg, 20% yield). Mass spectrum (apci) m/z = 436.2 (M+H).1H NMR (CD3OD) delta 9.05 (s, 1H), 8.15 (s, 1H), 7.47 (s, 1H), 7.28 (d, J = 9.6 Hz, 1H), 7.00 (d, J = 9.6 Hz, 1H), 6.97 (s, 1H), 5.16 (m, 1H), 4.75 (m, 1H), 3.65 (s, 3H), 3.45 (q, J = 7.2 Hz, 2H), 2.50-2.31 (m, 4H), 1.99-1.86 (m, 4H), 1.38 (t, J = 7.2 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,1227594-89-9, its application will become more common.

Reference:
Patent; ARRAY BIOPHARMA INC.; ALLEN, Shelley; BOYS, Mark Laurence; COOK, Adam; GAUDINO, John; HINKLIN, Ronald Jay; LAIRD, Ellen; MCNULTY, Oren T.; METCALF, Andrew T.; NEWHOUSE, Brad; ROBINSON, John E.; (545 pag.)WO2019/113190; (2019); 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.17282-01-8, name is 3-Bromo-2-fluoro-5-picoline, molecular formula is C6H5BrFN, molecular weight is 190.01, as common compound, the synthetic route is as follows.Safety of 3-Bromo-2-fluoro-5-picoline

Synthesis of Example 9: Intermediate 9a): [Show Image] A flame dried Schlenk flask was charged with 3-bromo-2-fluoro-5-picoline (1.00 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (129 mg), copper(I) iodide (60 mg), and dry N,N-dimethylacetamide (7 ml). The resulting mixture was degassed with atternating vacuum/argon purges. Then 1-tert-butoxycarbonylpiperidin-4-yl)(iodo)zinc (7.37 mmol, prepared as described in above) was added. The mixture was degassed once again and then heated to 80 C overnight. The mainpart of N,N-dimethylacetamide was then evaporated and the remainder was taken up in a mixture of EtOAc and water (100 ml each). The mixture was then filtered through Celite and transferred into a separatory funnel. The phases were separated and the water layer was extracted with EtOAc (3 x 50 ml). The combined organic layer was washed with water and brine (100 ml each), dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by column chromatography to furnish the desired compound in form of a white solid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,17282-01-8, 3-Bromo-2-fluoro-5-picoline, and friends who are interested can also refer to it.

Reference:
Patent; Santhera Pharmaceuticals (Schweiz) AG; EP2019100; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 886365-47-5, 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 886365-47-5, name is 1-(5-Bromo-2-chloropyridin-3-yl)ethanone. This compound has unique chemical properties. The synthetic route is as follows.

A mixture of 1-(5-bromo-2-chloropyridin-3- yl)ethanone (980 mg, 3.97 mmol) and N,N-dimethylformamide dimethyl acetal (4.0 mL, 30 mmol) was stirred at 90C for 90 minutes in an oil bath. The mixture was cooled to room temperature, and concentrated under reduce pressure. The residue was diluted by addition of ethanol (13 mL) and water (6.5 mL), acetic acid (1.6 mL, 28 mmol) and methyl (2S)-2-hydrazinylpropanoate hydrochloride (0.859 g, 5.56 mmol) obtained in Example (16a) was added thereto at room temperature, and the mixture was stirred at 90C for 4 hours in an oil bath. The mixture was cooled to room temperature, and neutralized by addition of a 2.0 mol/L aqueous solution of sodium hydroxide, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. After filtration, the solvent was distilled off under reduced pressure to obtain a crude product of (2S)-2-[5-(5-bromo-2- chloropyridin-3-yl) -1H-pyrazol-1-yl]propanoic acid (1.39 g) as a mixture containing a positional isomer. To a solution of the crude product of (2S)-2-[5-(5-bromo-2- chloropyridin-3-yl) -1H-pyrazol-1-yl]propanoic acid (1.31 g) obtained in the above step in tetrahydrofuran (10 mL), a 0.92 mol/L solution of boran-tetrahydrofuran complex in tetrahydrofuran (6.5 mL, 6.0 mmol) was added under ice cooling, the mixture was stirred at the same temperature as above for 10 minutes and subsequently stirred at room temperature for 20 hours. The mixture was cooled in an ice water bath, a 1.0 mol/L aqueous solution of sodium hydroxide was added thereto, followed by extraction with a mixed solvent of ethyl acetate/nhexane = 4/1. The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. After filtration, the solvent was distilled off under reduced pressure to obtain a crude product of (2S)-2-[5-(5-bromo-2- chloropyridin-3-yl) -1H-pyrazol-1-yl]propan-1-ol (760 mg) as a mixture containing a positional isomer. To a solution of the crude product of (2S)-2-[5-(5-bromo-2- chloropyridin-3-yl) -1H-pyrazol-1-yl]propan-1-ol (760 mg) as a mixture containing positional isomers obtained in the above step in N,N-dimethylformamide (50 mL) was added potassium carbonate (829 mg, 6.00 mmol) at room temperature, and the mixture was stirred at 120C for 2 hours in an oil bath. The reaction mixture was cooled, and diluted by addition of a saturated aqueous solution of ammonium chloride, followed by extraction with a mixed solvent of ethyl acetate/n-hexane = 4/1. The organic layer was washed with a saturated aqueous solution of ammonium chloride and a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. After filtration, the solvent was distilled off under reduced pressure, the residue was purified in an automatic chromatography apparatus (Yamazen Co. Ltd., High-flashTM column Amino, n-hexane/ethyl acetate = 96/4- 66/34) to obtain the title compound (597 mg, yield for 3 steps: 54%)?H NNR spectrum (CDC13, 400MHz) oe: 8.26 (1H, d, J =2.4 Hz), 8.19 (1H, d, J= 2.4 Hz), 7.55 (1H, d, J=1.8 Hz), 6.66 (1H, d, J = 1.8 Hz), 4.95-4.89 (1H, m),4.59 (1H, dd, J = 13.1, 4.6 Hz), 4.44-4.43 (1H, m), 1.64 (3H, d, J= 7.3 Hz).

According to the analysis of related databases, 886365-47-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; DAIICHI SANKYO COMPANY, LIMITED; SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE; MIYAZAKI, Shojiro; INUI, Masaharu; KUROSAKI, Yasunobu; YAMAMOTO, Yuko; IZUMI, Masanori; SOMA, Kaori; PINKERTON, Anthony; KISHIDA, Masamichi; (309 pag.)WO2018/119444; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 59942-87-9, 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 59942-87-9 as follows.

A stirred solution of pyrazolo[l,5-a]pyridin-2-ol (27-1; 0.9 g, 0.0067 mol) in POCl3 (10 mL) was heated in a sealed tube at 145 C for 6 h. The reaction mixture was cooled to room temperature, poured into ice cold water (20 mL) and extracted with dichloromethane (3 x 20 mL). The combined organic layers were washed with saturated sodium chloride, dried over sodium sulphate and concentrated under vacuum to afford the crude compound, which was purified by column chromatography to obtain the title compound. 1H NMR (400 MHz, DMSO-d6) 6 8.36 – 8.34 (d, J =1.2 Hz, 1 H), 7.44-7.42 (d, J= 9.2 Hz, 1 H), 7.17-7.13 (m, 1 H), 6.78-6.74 (m, 1 H), 6.43 (s, 1 H). MS (M+l): 152.8.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,59942-87-9, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; BENNETT, D. Jonathan; CAI, Jaiqiang; CARSWELL, Emma; COOKE, Andrew; HOYT, Scott, B.; LONDON, Clare; MACLEAN, John; PARK, Min, K.; RATCLIFFE, Paul; XIONG, Yusheng; SAMANTA, Swapan Kumar; KULKARNI, Bheemashankar, A.; WO2013/43521; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 89466-17-1, Adding some certain compound to certain chemical reactions, such as: 89466-17-1, name is 6-Bromo-5-methylpyridin-2-amine,molecular formula is C6H7BrN2, 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 89466-17-1.

To a solution of 6-bromo-5-methylpyridin-2-amine (2.50 g, 13.4 mmol) in i-PrOH (25 mL) was added dimethylformamid-dimethylacetal (2.23 g, 18.7 mmol). The solution was stirred at 85C for 3 h under Ar, cooled to rt and used directly in the next step without further purification.

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. 89466-17-1, 6-Bromo-5-methylpyridin-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; PHENEX-FXR GMBH; GEGE, Christian; BIRKEL, Manfred; HAMBRUCH, Eva; DEUSCHLE, Ulrich; KREMOSER, Claus; (203 pag.)WO2019/16269; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 727356-19-6, Adding some certain compound to certain chemical reactions, such as: 727356-19-6, name is 2-Bromo-6-(chloromethyl)pyridine,molecular formula is C6H5BrClN, 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 727356-19-6.

Compound 7 (0.15 g, 0.57 mmol) was dissolvedin N,N-dimethylacetamide (2 mL) and sodium hydride (0.017 g, 0.7 mmol) added. The mixture was stirred at room temperature for 20 minutes. Then compound 15(0.2 g, 0.77 mmol) was added and the mixture was heated at ~ 60C in a sand-bath for 2 h. The mixture was diluted with ethyl acetate (40 mL) and brine (15 mL).The organic phase was separated, dried over Na2SO4, filtered and the solvents removed. The residue was purified by chromatography on silica using dichloromethane to elute excess benzyl chloride, followed by dichloromethane/acetone (95/5) to afford 18 as yellow oil (0.2 g, 82 %). 1H-NMR (400 MHz, CDCl3): delta= 1.40 (s, 9H), 2.86 (t, 2H), 4.48 (t, 2H), 5.25 (s, 2H), 6.88 (d, 1H), 7.17 (d, 1H), 7.32 (d, 1H), 7.45 (t, 1H), 7.58 (t, 1H), 7.74 (d, 1H).

According to the analysis of related databases, 727356-19-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Kroth, Heiko; Sreenivasachary, Nampally; Hamel, Anne; Benderitter, Pascal; Varisco, Yvan; Giriens, Valerie; Paganetti, Paolo; Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas; Bioorganic and Medicinal Chemistry Letters; vol. 26; 14; (2016); p. 3330 – 3335;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 1026796-81-5, 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 1026796-81-5 as follows.

Step 2: N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide To a mixture of N-(4-bromopyridin-2-yl)acetamide (17.2 g, 80 mmol, 1.0 equiv.), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (26.4 g, 104 mmol), Pd(dppf)Cl2 (11.7 g, 16 mmol) and KOAc (23.6 g, 240 mmol) under an atmosphere of nitrogen was added anhydrous DMF (1500 mL). The mixture was allowed to stir at 80 C. for 3.5 h. The solvent was removed and the residue was diluted with EtOAc (1000 mL). Activated carbon (100 g) was added. The slurry was heated at reflux for 5 min and then filtered. The organic solution was concentrated and the residue was re-crystallized from EtOAc to give N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (6.1 g, 29%) as a white solid. 1H NMR (400 MHz, DMSO-d6): delta 1.29 (s, 12H), 2.09 (s, 3H), 7.24 (dd, J=6.0, 1.2 Hz, 1H), 8.30-8.33 (m, 2H), 10.47 (br 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,1026796-81-5, its application will become more common.

Reference:
Patent; MILLENNIUM PHARMACEUTICALS, INC.; Chau, Ryan W.; Cullis, Courtney A.; Duffey, Matthew O.; Gipson, Krista E.; Hu, Yongbo; Li, Gang; Sintchak, Michael D.; Vos, Tricia J.; US2013/165464; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 79055-63-3, 2-Chloro-6-methylpyridin-4-amine, 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, 79055-63-3, blongs to pyridine-derivatives compound. SDS of cas: 79055-63-3

Lithium bis(trimethylsilyl)amide in THF (4.23 mL, 1 M, 4.23 mmol) was added to a solution of ethyl 4-[(3,3-difluoro-l-methyl-cyclobutyl)sulfamoyl]-3-fluoro-l -methyl-pyrrole -2-carboxylate (500 mg, 1.41 mmol) and 2-chloro-6-methyl-pyridin-4-amine (316 mg, 1.76 mmol) in THF (7.6 mL) and the mixture was stirred for 2 hours at room temperature. The mixture was quenched with NH4C1 solution, diluted with brine and extracted with EtOAc (25mL). The combined extracts were dried on Na2S04, filtered and concentrated in vacuo. The residue was purified by column chromatography using a gradient from 10 till 100% EtOAc in heptane. The product fractions were concentrated. The residue was crystallised out of isopropanol, the crystals were collected on a filter and dried overnight in vacuo at 50C, resulting in compound (0650) 130 (378 mg) as a white powder. Method B: Rt: 1.08 min. m/z: 449.1 (M-H)~ Exact mass: 450.1. DSC: From 30 to 300 C at 10C/min, peak 217.7 C. 1H NMR (400 MHz, DMSO-d6) delta ppm 1.42 (s, 3 H), 2.42 (s, 3 H), 2.52 – 2.63 (m, 2 H), 2.79 – 2.99 (m, 2 H), 3.81 (s, 3 H), 7.47 – 7.51 (m, 1 H), 7.56 (d, J=4.6 Hz, 1 H), 7.60 – 7.64 (m, 1 H), 8.24 (s, 1 H), 10.45 (s, 1 H)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,79055-63-3, its application will become more common.

Reference:
Patent; JANSSEN SCIENCES IRELAND UC; VANDYCK, Koen; HACHE, Geerwin Yvonne Paul; LAST, Stefaan Julien; ROMBOUTS, Geert; VERSCHUEREN, Wim Gaston; RABOISSON, Pierre Jean-Marie Bernard; WO2015/118057; (2015); 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. 1160791-13-8, name is 2-Amino-6-bromothiazolo[5,4-b]pyridine. This compound has unique chemical properties. The synthetic route is as follows. Application In Synthesis of 2-Amino-6-bromothiazolo[5,4-b]pyridine

6-Bromo-[1 ,3]thiazolo[5,4-b]pyridin-2-amine (0.1 g, 0.43 mmol) was dissolved in N-methyl-2-pyrrolidone (1.5 mE) and ethyl 3-bromo-2-oxopropanoate (64 pi, 0.43 mmol) added dropwise. The reaction was stirred at room temperature for 1 hour then heated to 60 C. overnight. The reaction was cooled then water/ice added. The resulting precipitate was isolated by vacuum filtration. The red solid was further dried in a vacuum oven to give the title compound. ?H NMR(500 MHz, DMSO) 9.05 (s, 1H), 8.95 (d, J=2.1 Hz, 1H), 8.74 (d, J=2.1 Hz, 1H), 4.32 (q, J=7.1 Hz, 2H), 1.33 (t, J=7.1 Hz, 3H). Tr(MS10)=1.55 mi mlz (ES(M+H)328, 329

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, 1160791-13-8, 2-Amino-6-bromothiazolo[5,4-b]pyridine.

Reference:
Patent; CHDI Foundation, Inc.; Dominguez, Celia; Wityak, John; Bard, Jonathan; Brown, Christopher John; Prime, Michael Edward; Johnson, Peter David; Krulle, Thomas Martin; Clark-Frew, Daniel; Higgins, Duane; Mills, Matthew Robert; Marston, Richard Waldron; Coe, Samuel; Jones Green, Samantha Louise; Hayes, Sarah; (71 pag.)US2017/56535; (2017); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem