Month: April 2022

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.298709-29-2, name is 3,5-Difluoropicolinonitrile, molecular formula is C6H2F2N2, molecular weight is 140.0903, as common compound, the synthetic route is as follows.SDS of cas: 298709-29-2

Intermediate 45 l-(3,5-Difluoropyridin-2-yr)ethanoneA solution of methylmagnesium bromide (36.8 ml, 117.78 mmol) in THF (50ml) was stirred under N2 and cooled to -78C. 3,5-difluoropicolinonitrile (15.0 g, 107.07 mmol) in THF (50 ml) was added drop wise with an addition funnel at such a rate that the internal temp, was kept below -4C. After the addition was complete, the reaction was poured into a IM HCl (100 ml, chilled in an ice bath). The reaction was stirred at 00C for 30 minutes and r.t. for 30 minutes. To this solution 150 ml of EtOAc was added to extract product. The aqueous phase was neutralized to pH9 with NaHCO3 and extracted with EtOAc (2 X 20 ml). The organic phase were combined and the volatiles were removed under reduced pressure. Purification by ISCO (0-10% EtOAc- hexanes) gave the title compound as light yellow oil. LC-MS: 158 [M+H].

At the same time, in my other blogs, there are other synthetic methods of this type of compound,298709-29-2, 3,5-Difluoropicolinonitrile, and friends who are interested can also refer to it.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2008/132502; (2008); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 132521-70-1, 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 132521-70-1 as follows.

A mixture of 6-(4-methylpiperazin- 1 -yl)nicotinicacid (50 mg, 0.226 mmol), tert-butyl 2-amino-4-(thran-3- yl)phenylcarbamate (62 mg, 0.226 mmol) and EDCI (95 mg, 0.5 mmol) in pyridine (5 mE) was stirred at room temperature for overnight. The mixture was poured into water (20 mE) and extracted with EA to afford crude (170 mg, crude).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,132521-70-1, its application will become more common.

Reference:
Patent; Regenacy Pharmaceuticals, LLC; van Duzer, John H.; Mazitschek, Ralph; (123 pag.)US2018/141923; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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. 1186608-73-0, name is 3-Methyl-1H-pyrazolo[3,4-b]pyridin-5-amine. A new synthetic method of this compound is introduced below., HPLC of Formula: C7H8N4

EXAMPLE 4: 5-Bromo-3-methyl-lH-pyrazolo-r3,4-&1pyridineA stirred solution 3-Methyl-lH-pyrazole[3,4-b]pyridin-5-amine (200mg, 1.35mmol) in 48% hydrobromic acid (1.46ml, 27.02mmol) and water (1.5ml) was cooled to -5 C. A solution of sodium nitrite (lOOmg, 1.47mmol) in water (0.5ml) was added to this reaction mixture at 0 C. Then this reaction mixture was added to a suspension of copper (I) bromide (300mg, 2.02mmol) in 48% hydrobromic acid (0.4ml) maintained at 0C. Reaction mixture was stirred for 4h at RT. Reaction mixture was extracted with ethyl acetate. The extract was washed with water (3x 20ml) and sodium carbonate solution (2x 15ml). The combined organic layer was dried over anhydrous sodium sulphate, filtered and concentrated. Purification was done by flash column over 230-400 mesh silica gel eluting with 25% ethyl acetate/ petroleum ether to get the desired product 6, lOOmg (Yield -35%) as white solid. The product was confirmed by 1HNMR and MS spectrum analysis. 1H NMR (400 MHz, CDC13) delta: 10.92 (bs, 1H), 8.59 (s, 1H), 8.21 (s, 1H), 2.59 (s, 1H); MS: 212 (M+l).

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, 1186608-73-0, 3-Methyl-1H-pyrazolo[3,4-b]pyridin-5-amine.

Reference:
Patent; ARRIEN PHARMAEUTICALS LLC; VANKAYALAPATI, Hariprasad; APPALANENI, Rajendra, P.; REDDY, Y., Venkata Krishna; WO2012/135631; (2012); 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. 915006-52-9, name is 6-Bromo-2-iodopyridin-3-amine, the common compound, a new synthetic route is introduced below. Application In Synthesis of 6-Bromo-2-iodopyridin-3-amine

To a mixture of 6-bromo-2-iodopyridin-3-amine (100 mg, 0.34 mmol), 1,2-dimethoxy-4-(prop-1-yn-1-yl)benzene (74 mg, 0.42 mmol), lithium chloride (18 mg, 0.42 mmol), sodium carbonate (180 mg, 1.68 mmol) and Pd(dppf)Cl2 (12.5 mg, 0.017 mmol) in a screw cap vial was added DMF (2 mL). The vial was fitted with a Teflon-lined septum cap. The system was evacuated under vacuum (via a needle from a nitrogen/vacuum manifold line) and backfilled with nitrogen gas. The procedure was repeated three times. The needle was removed and the vial was heated at 100 C. for 16 h. LCMS analysis shows formation of two isomers, in approximately 3:1 ratio. 1H NMR analysis suggested the major product to be 5-bromo-2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridine (5A-1). The reaction mixture was diluted with EtOAc (50 mL), poured into a separatory funnel and washed with 10% aqueous LiCl solution (2*10 mL) and saturated aqueous NaCl solution (10 mL), dried (Na2SO4), filtered and the filtrate was concentrated. The crude product was dissolved in a small amount of DCM and purified on a silica gel column chromatography with a 15 min gradient from 0%-100% DCM/EtOAc to afford 5-bromo-2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridine (Intermediate 5A-1) that was contaminated with Intermediate 5A-2, 5-bromo-3-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridine, m/z (303, M+1), 80 mg (67%). To a mixture containing 5-bromo-2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridine (Intermediate 5A-1) and Intermediate 5A-2 (100 mg, 0.29 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)-carboxylate (111 mg, 0.36 mmol), and Pd(dppf)C12 (10.5 mg, 0.014 mmol) in a screw cap vial was added THF (2.5 mL) followed by 3M aqueous solution of tripotassium phosphate (0.10 mL, 0.3 mmol). The vial was fitted with a Teflon lined septum cap. The system was evacuated under vacuum (via a needle from a nitrogen/vacuum manifold line) and backfilled with nitrogen gas. The procedure was repeated three times. The needle was removed and the vial was heated at 75 C. for 3 h. The reaction mixture was cooled to room temperature and treated with saturated aqueous NaCl solution (5 mL) and extracted with ethyl acetate (3*10 mL). The extracts were combined, dried (Na2SO4), filtered and concentrated. The crude product was dissolved in a small amount of DCM and purified on silica gel column chromatography eluting with a 10 min gradient from 5%-100% DCM/EtOAc. No separation was observed. A mixture of tert-butyl 4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 5B) and the regioisomer tert-butyl 4-(3-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1 (2H)-carboxylate was isolated (100 mg, 77% yield), m/z (550, M+1) and was used as such in subsequent step. A mixture of tert-butyl 4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 5B) and regioisomer tert-butyl 4-(3-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (95 mg, 0.21 mmol) was dissolved in MeOH (5 mL) and transferred to a Parr bottle. The mixture was purged with nitrogen. Pearlman’s Catalyst (25 mg, 0.036 mmol) was added and the bottle was pressurized with hydrogen gas (50 psi) and shaken for 22 h. The reaction mixture was filtered through a pad of Celite and the filtrate was concentrated. The resulting residue was dissolved in a small amount of DCM and charged to a silica gel column, which was eluted over a 10 min gradient with 1%-5% MeOH/DCM to afford a mixture of tert-butyl 4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 5C) and the regioisomer tert-butyl 4-(3-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1 (2H)-carboxylate (82 mg, 80%), m/z (452, M+H).

The synthetic route of 915006-52-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; Dyckman, Alaric J.; Dodd, Dharmpal S.; Mussari, Christopher P.; Sherwood, Trevor C.; Whiteley, Brian K.; Gilmore, John L.; Kumar, Sreekantha Ratna; Pasunoori, Laxman; Srinivas, Pitani Veera Venkata; Duraisamy, Srinivasan Kunchithapatham; Hegde, Subramanya; Anumula, Rushith Kumar; US2019/185469; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 26163-03-1, 3-Bromo-5-chloropyridin-2-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, 26163-03-1, blongs to pyridine-derivatives compound. Application In Synthesis of 3-Bromo-5-chloropyridin-2-amine

a sobthDn of 2-amiao-Thlznio-&cIueolopydin? (10.0 g, 4S.2 mmol7 Ark Phmm iii Nfl dim?thyl.fcamumide (2] niL) was ailed DMF-DMA (17.2 g, 145 nutol) anl the nthrthre was sbned13] C fca abc?at 18 K The mixbare was cooled aat evapcnted to thyness. To an ice cooled Hn sob fioiiofthebrcwiisolid iiiMeOH (JO mL) ardpyridim (7.8QniL, %nutiol)was added hthor,r1anthie-o-sulforth td (73g, 675 nmnol). TIE rac&iwas allowed to wanr to thciat 25anl stind fbr about 13 K The nuethr? was evapra±ed and the solid iesithie was dissohd in DCM (150 mL) aid washel with ;aturated o1±uaubicaabointe (10 niL), water (20] niL) ard biine (10 nL). The oigai& nuethre was filtered though a Eiote phase sepantc to renrn iesi&ial wateraiid evapcnted to thyrs to give ?-Ch1 [LZ4]1rio1o[L5-a]pth2e as an cnie soli4 whck was used iii th n?xttep witlout fint1r purificaiiou.. (.l g, 64% nude): ?H NMR (CDC1.)i5 2155(d, 1 1.3Hz, 1H), 239 (s, 1H), 7SJ (, 1 1.7Hz, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,26163-03-1, its application will become more common.

Reference:
Patent; ABBVIE INC.; ABBVIE PHARMACEUTICAL TRADING (SHANGHAI) CO., LTD.; FRIEDMAN, Michael M.; COX, Philip; FRANK, Kristine E.; HOEMANN, Michael Z.; OSUMA, Augustine; WILSON, Noel S.; XU, Xiangdong; WO2015/157955; (2015); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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. 3430-26-0, name is 2,5-Dibromo-4-methylpyridine. A new synthetic method of this compound is introduced below., Product Details of 3430-26-0

Intermediate 43. Step 1; 5-bromo-4-methylpicolinic acid To a solution of 2,5-dibromo-4-methylpyridine (3 g, 11.96 mmol) in anhydrous toluene (40 ml)) was added BuLi (5.74 ml, 14.35 mmol) at -78 °C dropwise. The reaction mixture was stirred at – 78 °C for 1 h. Then the reaction mixture was poured into a 100 mL beaker with dry carbon dioxide (4 g, 91 mmol). The reaction mixture was stirred at 20 °C for another 10 minutes. Then the mixture was poured into saturated citric acid and a yellow precipitate was formed. The suspension was filtered and the solid was collected, dried in vacuo to give 5-bromo-4- methylpicolinic acid. 1HNMR (400 MHz, DMSO-i): delta = 8.71 (s, 1 H), 7.99 (s, 1 H), 2.40 (s, 3 H). MS: 215.9 (M+l) ppm.

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, 3430-26-0, 2,5-Dibromo-4-methylpyridine.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIU, Jian; KOZLOWSKI, Joseph, A.; ALHASSAN, Abdul-Basit; BOGA, Sobhana Babu; GAO, Xiaolei; GUIADEEN, Deodialsingh; WANG, Jyhshing; XU, Jiayi; YU, Wensheng; YU, Younong; CAI, Jiaqiang; LIU, Shilan; WANG, Dahai; WU, Hao; YANG, Chundao; (211 pag.)WO2016/109221; (2016); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 76015-11-7, 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. 76015-11-7, name is 3-Methoxy-2-methylpyridin-4(1H)-one. A new synthetic method of this compound is introduced below.

3-Methoxy-2-methyl-4(1H)-pyridone (27.8g, 0.2 mol) was added to phosphorus oxychloride (200 mL) and the resulting mixture was heated under nitrogen at 90 oC for 18 h. The homogeneousmixture was cooled to 20 oC and concentrated under reduced pressure.The residue was dissolved in ice-water. Adjustment of the solution to pH 12with 40% sodium hydroxideresulted in a turbid suspension which was extracted with dichloromethane (3 x100 mL). The combined organic extracts were combined, washed with water. After drying the extract with MgSO4,the DCM was removed by rotary evaporation to give the title product (30.2 g,96%). 1H NMR (CDCl3) d 8.14(d, 1H, J = 5.32 Hz), 7.17 (d, 1H, J = 5.10 Hz), 3.85 (s, 3H), 2.54 (s, 3H). m/z (ESI) 157.91 (M+ +1).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,76015-11-7, its application will become more common.

Reference:
Article; Maharvi, Ghulam M.; Bharucha, Adil E.; Fauq, Abdul H.; Bioorganic and Medicinal Chemistry Letters; vol. 23; 9; (2013); p. 2808 – 2811;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 717843-56-6, 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 717843-56-6 as follows.

To 3-bromo-2-methoxy-5-methylpyridine [CAS 717843-56-6] (1.0 g, 4.95 mmol) in 20 mL of dry tetrahydrofuran was added Q-Phos (1,2,3,4,5-pentaphenyl-1?-(di-tert-butylphosphino)ferrocene) (0.077 g, 0.109 mmol) and bis(dibenzylideneacetone)palladium (0.091 g, 0.099 mmol). A solution of freshly-prepared (1-(methoxycarbonyl)cyclopropyl)zinc(II) bromide (2.419 g, 9.90 mmol) in tetrahydrofuran (0.45 mmol/mL, 17 mL) was added via a stainless steel cannula under nitrogen pressure. The mixture was stirred at ambient temperature for 40 minutes. Dichloromethane and saturated aqueous NH4Cl were added. The organic layer was washed with brine and concentrated. The residue was purified via chromatography on a 40 g silica gel cartridge, eluting with ethyl acetate in 48 heptane at 0-50% gradient to yield 136 methyl 1-(2-methoxy-5-methylpyridin-3-yl)cyclopropanecarboxylate which was dissolved in 28 methanol (10 mL) and 6M 137 aqueous lithium hydroxide (3 mL) and stirred at 50 C. for 15 hours. The solvent was removed, and 25 water (10 mL) was added. The aqueous layer was extracted with ethyl acetate (10 mL×2). The aqueous layer was adjusted pH 1-2 and extracted with dichloromethane (30 mL×3), and the extracts washed with brine, dried over MgSO4 and concentrated to provide the 138 title compound which used in next step without further purification. MS (APCI+) m/z 208 (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,717843-56-6, its application will become more common.

Reference:
Patent; AbbVie S.a.r.l.; Galapagos NV; Altenbach, Robert J.; Bogdan, Andrew; Couty, Sylvain; Desroy, Nicolas; Gfesser, Gregory A.; Housseman, Christopher Gaetan; Kym, Philip R.; Liu, Bo; Mai, Thi Thu Trang; Malagu, Karine Fabienne; Merayo Merayo, Nuria; Picolet, Olivier Laurent; Pizzonero, Mathieu Rafael; Searle, Xenia B.; Van der Plas, Steven Emiel; Wang, Xueqing; Yeung, Ming C.; (189 pag.)US2019/77784; (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.6945-67-1, name is 2-Bromo-4-nitropyridine, molecular formula is C5H3BrN2O2, molecular weight is 202.99, as common compound, the synthetic route is as follows.Product Details of 6945-67-1

The 2-[1-hydroxy-1-[4-(naphth-2-ylmethoxy)pyrid-2-yl]propyl]thiazole used as a starting material was obtained as follows: 2-Naphthylmethanol was reacted with 2-bromo-4-nitropyridine (Chem. Abstracts, 1951, 45, 9536) using the conditions described in the first paragraph of the portion of Example 4 which is concerned with the preparation of starting materials except that the reaction mixture was stirred at ambient temperature for 2 hours. There was thus obtained 2-bromo-4-(naphth-2-ylmethoxy)pyridine in 80% yield, m.p. 99-100 C.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,6945-67-1, 2-Bromo-4-nitropyridine, and friends who are interested can also refer to it.

Reference:
Patent; ICI Pharma; Imperial Chemical Industries PLC; US5089513; (1992); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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. 1221171-70-5, name is 2-Chloro-6-(trifluoromethoxy)pyridine. A new synthetic method of this compound is introduced below., SDS of cas: 1221171-70-5

c) 6-chloro-2-(trifluoromethoxy)-3-(trimethylsilyl)pyridine (1-6); A LDA solution was prepared from n-BuLi 2.5M in hexane (22 mL; 56.80 mmol; 1.1 eq) and diisopropylamine (8 mL; 56.80 mmol; 1.1 eq) in THF (40 mL) at 0C. To the LDA solution at -78 C, a solution of 2-chloro-6-(trifluoromethoxy)pyridine (10.2 g; 51.64 mmol; 1 eq) in THF (40 mL) was added dropwise over 30 minutes. The solution was stirred at -78 C for 2 hours, after what TMSCI (7.20 mL; 56.80 mmol; 1.1 eq) was added dropwise. The reaction mixture was allowed to warm up to room temperature and stirred 1 hour. Water (120 mL) was then added. The aqueous layer was extracted with diethylether (3 x 120 mL), and the combined organic layers were dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude was purified on silica gel using petroleum ether (100 %) as an eluent to afford 6-chloro-2- (trifluoromethoxy)-3-(trimethylsilyl)pyridine in 94 % yield as a colorless oil.1H- MR (CDC13): delta (ppm) 0.33 (s, 9H); 7.21 (d, 1H); 7.77 (d, 1H).

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, 1221171-70-5, 2-Chloro-6-(trifluoromethoxy)pyridine.

Reference:
Patent; VIVALIS; CIAPETTI, Paola; TROUCHE, Nathalie; VENKATA PITHANI, Subhash; GUEDAT, Philippe; BERECIBAR, Amaya; WO2012/93174; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem