Day: March 22, 2022

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

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

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

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

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

Adding a certain compound to certain chemical reactions, such as: 700811-29-6, 2-Chloro-4-hydrazinopyridine, 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, Safety of 2-Chloro-4-hydrazinopyridine, blongs to pyridine-derivatives compound. Safety of 2-Chloro-4-hydrazinopyridine

A microwave reaction vessel was charged with 500 mg of (2-chloro- pyridin-4-yl) -hydrazine (3.48 mmol, 1. 3 equiv) and 848 mg g of N-cyano-N’-(2-phenyl- ISOUREIDO)-BENZENESULFONAMIDE (2.68 mmol, 1 equiv) in a mixture of NMP (5 mL) and diisopropylethylamine (1.4 mL). The sealed vessel was warmed to 220 C for 6 min via microwave irradiation. Upon cooling, the resulting solution was poured onto saturated aqueous sodium hydrogen carbonate (40 mL) and a yellow solid precipitated. The precipitate was collected by vacuum filtration and washed with water (3 X 10 ML). AFTER azeotropic drying (3 x 50 mL of acetonitrile) the dark yellow solid was used without further purification (723.1 mg, 74%); 1H NMR (400 MHz, (CD3) 2SO) 8 9.67 (1H, s), 8. 45 (1H, d, J= 6.3). 7.69 (6H, m), 7.12 (4H, br s); MS (ES) mle 366. 38, (ES) mle 364.49

At the same time, in my other blogs, there are other synthetic methods of this type of compound,700811-29-6, 2-Chloro-4-hydrazinopyridine, and friends who are interested can also refer to it.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; LEDEBOER, Mark W.; DAVIES, Robert J.; WO2005/13982; (2005); 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. 851386-40-8, name is 4-Chloro-2,5-difluoropyridine. This compound has unique chemical properties. The synthetic route is as follows. Safety of 4-Chloro-2,5-difluoropyridine

Diisopropylamine (30 g, 0.29 mol) was dissolved in anhydrous tetrahydrofuran (200 ml) and the nitrogen was removed.Cooling to -65 – 40 ,A solution of n-butyllithium / n-hexane (2.5 M, 105 ml)Stir the mixture for 30 minutes.4-chloro-2,5-difluoropyridine (50 g, 0.33 mol) obtained in the above step was slowly added dropwise at -65 C,After the dropwise addition, the mixture was stirred for 1 hour.A solution of methyl iodide (42 g, 0.29 mol)Dripping finished slowly rose to -50 ,And stirred for 1 hour,TLC reaction is complete.The reaction was quenched with saturated ammonium chloride solution,Methyl tert-butyl ether extraction reaction solution,The organic phase was washed with 2N hydrochloric acid,Then washed with water,Saturated sodium bicarbonate wash,Saturated with salt water,The organic phase was separated and dried over anhydrous sodium sulfate,filter,The filtrate was distilled off at 80 C to 120 C under atmospheric pressure,The remaining crude product at 0.09MPa at 70 ~ ~ 100 vacuum distillation of the product,A fraction of 65-80 C was collected to give the product 4-chloro-2,5-difluoro-3-methylpyridine (34.8 g, yield 64%).

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, 851386-40-8, 4-Chloro-2,5-difluoropyridine.

Reference:
Patent; Danuo Pharmaceutical (Suzhou) Co., Ltd.; Ding, Jun; He, Shijie; Zhuang, Zhijun; Ma, Zhenkun; (13 pag.)CN106432222; (2017); A;,
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. 15862-50-7, name is 3-Bromo-2-methoxy-5-nitropyridine, the common compound, a new synthetic route is introduced below. Recommanded Product: 3-Bromo-2-methoxy-5-nitropyridine

Step 1: tert-Butyl (1-(4-((2-methoxy-5-nitropyridin-3-yl)ethynyl)phenyl)cyclobutyl) carbamate: 3-Bromo-2-methoxy-5-nitropyridine (161 mg, 0.691 mmol) was stirred in 1 : 1 , Et3N/1 ,4-dioxane (1.5 mL) at RT and the reaction mixture degassed under an atmosphere of N2. The temperature was reduced to 0 C and Pd(‘Bu3P)2 (14.1 mg, 0.0276 mmol) was added. After 10 minutes, Cu(l)l (1.3 mg, 0.0092 mmol), followed by dropwise addition of tert-butyl (1-(4-ethynylphenyl)cyclobutyl)carbamate (125 mg, 0.461 mmol) in Et3N (0.75 mL). After 4 hours, the solvents were removed in vacuo, coevaporating to remove residual Et3N. The residue was dissolved in DCM, filtered through Celite, washing with DCM. The solvents were removed in vacuo and the remaining residue was purified by flash chromatography (Si02, 0?25%, EtOAc in n- hexane) to give the title compound (127 mg, 65%) as a pale yellow solid. 1H NMR (500 MHz, CDCI3): delta 9.00 (d, 1 H), 8.50 (d, 1 H), 7.55 (d, 2H), 7.44 (d, 2H), 5.13 (s, 1 H), 4.15 (s, 3H), 2.62-2.43 (m, 4H), 2.18-2.08 (m, 1 H), 1.94-1.83 (m, 1 H). 1.49-1.05 (m, 9H).

The synthetic route of 15862-50-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ALMAC DISCOVERY LIMITED; BELL, Mark, Peter; O’DOWD, Colin, Roderick; ROUNTREE, James, Samuel, Shane; TREVITT, Graham, Peter; HARRISON, Timothy; MCFARLAND, Mary, Melissa; WO2011/55115; (2011); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 1346148-32-0, 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. 1346148-32-0, name is Methyl 5-fluoro-3-methylpicolinate. A new synthetic method of this compound is introduced below.

To a solution of 5-fluoro-3-methyl-pyridine-2-carboxylic acid methyl ester (1.28 g) inMeOH (6 ml) was added at 22C a solution of lithium hydroxide mono hydrate (636 mg) in water (3 ml) and stiring was continued for 16 h. The mixture was diluted with water, the MeOH was evaporated at reduced pressure and the pH was adjusted to 1 using 1 N aqueous HC1. The aqueous layer was extracted with AcOEt, the organic layer was dried, evaporated and the residue was crystallized from AcOEt/n-heptane to give the title compound (1.02 g) as a pale yellow solid. MS: m/z = 153.7 [M-H]

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1346148-32-0, Methyl 5-fluoro-3-methylpicolinate, and friends who are interested can also refer to it.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; SIENA BIOTECH S.P.A.; BANNER, David; GUBA, Wolfgang; HILPERT, Hans; HUMM, Roland; MAUSER, Harald; MAYWEG, Alexander, V.; NARQUIZIAN, Robert; POWER, Eoin; ROGERS-EVANS, Mark; ROMBACH, Didier; WOLTERING, Thomas; WOSTL, Wolfgang; WO2011/138293; (2011); 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. 71670-70-7, name is 2-(Chloromethyl)-5-methylpyridine hydrochloride, the common compound, a new synthetic route is introduced below. Application In Synthesis of 2-(Chloromethyl)-5-methylpyridine hydrochloride

Example 100 l -(3-hydroxybutyl)-3-methyl-7-((5-methylpyridin-2-yl)methyl)-8-(3- (trifl To a solution of l -(3-hydroxybutyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-lH-pur ne- 2,6(3H,7H)- dione (50 mg, 0.121 mmol, intermediate 57) in DMF (3 mL) was added 2- (chloromethyl)-5-methylpyridine hydrochloride (30 mg, 0.182 mmol, intermediate 50), followed by potassium carbonate (50 mg, 0.363 mmol) and TBAI (10mg,0.027mmol). The reaction was stirred at 65 C overnight. The reaction was cooled and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude product, which was purified by preparative HPLC to give l -(3- hydroxybutyl)-3-methyl-7-((5-methyl^ purine-2,6(3H,7H)-dione (20 mg, 31.9% yield) as white solid. ‘H-NMR (CD3OD) delta 8.319(s,l H), 7.663-7.640(d,l H),7.553-7.510(t,l H), 7.348-7.316(m,3H), 7.233-7.208(m, lH), 5.609(s,2H), 4.1 12-4.004(m,2H), 3.763-3.731(m, l H), 3.457(s,3H), 2.339(s,3H), 1.758- 1 .698(m,2H), 1.197-1.182(d,2H). LCMS retention time 2.714 min; LCMS MH+ 520.

The synthetic route of 71670-70-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; HYDRA BIOSCIENCES, INC.; CHENARD, Bertrand; GALLASCHUN, Randall; WO2014/143799; (2014); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem