Category: pyridine-derivatives

Electric Literature of 234108-73-7 , The common heterocyclic compound, 234108-73-7, name is tert-Butyl 2-chloropyridine-4-carbamate, molecular formula is C10H13ClN2O2, 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.

A solution of 4-amino-2-chloropyridine (1.28 gm, 10 mmol) and di-tert-butyl dicarbonate (2.21 gm, 10.1 mmol) in THF (20 mL) was cooled to 00C and a solution of IM lithium bis(trimethylsilyl)amide in THF ( 20 mL, 20 mmol) was added slowly maintaining the temperature below 00C. The reaction was allowed to warm to room temperature over one hour and then quenched by the addition of 1.5 N aqueous ammonium chloride (15 mL). After stirring for several hours the reaction was extracted into ethyl acetate, washed with brine, the organic layer dried (Na2SO4), filtered and evaporated. The residue was triturated with diethyl ether give pure tert-butyl (2-chloropyridin-4- yl)carbamate. The mother liquors were chromatographed on silica gel eluting with 25 – 45% ethyl acetate/ hexane to afford more product. EPO A solution of tert-butyl (2-chloropyridin-4-yl)carbamate (1.14 gm, 5 mmol) in dry THF (20 mL) was cooled to -700C under an inert atmosphere and 1.7 M t-butyl lithium/pentane (8 mL, 13.5 mmol) was slowly added. The reaction was stirred for two hours and then dry DMF (1.2 mL, 15.5 mmol) was added. The reaction was allowed to slowly warm to room temperature over a three hour period. The reaction mixture was quenched with 3 N HCl (12 mL) and diluted with diethyl ether. The ether layer was washed with aqueous NaHCtheta3, dried (over Na2SO4), filtered and evaporated. The residue was triturated with cold diethyl ether to give pure t-butyl (2-chloro-3-formylrhoyridin-4- yl)carbamate. The mother liquors were chromatographed on silica gel eluting with 15-20% ethyl acetate/hexane to give additional product. 1H-NMR(5OO MHz, CDCI3): deltall.O (IH, br s), 10.52 (IH, s), 8.38 (IH, d, J= 6 Hz), 8.31 (IH, d, J= 6 Hz), 1.54 (9H, s); m/e (m+1): 257.2.

The synthetic route of 234108-73-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK & CO., INC.; WO2006/135627; (2006); A2;,
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.1211541-93-3, name is 5-Fluoro-2-methoxypyridin-3-amine, molecular formula is C6H7FN2O, molecular weight is 142.13, as common compound, the synthetic route is as follows.name: 5-Fluoro-2-methoxypyridin-3-amine

To a solution of XII-1 (0.50 g, 1 .97 mmol) in pyridine (10 mL) was added X-1 (0.18 g, 1 .25 mmol) and DMAP (0.012 g, 0.09 mmol). The reaction mixture was heated at 80 C for 16h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction mixture was concentrated under vacuum. The residue was diluted with H20 (100 mL), 1 N HCI (50 mL) and extracted with EtOAc (100 mL). The organic layer was separated, dried over anhydrous Na2S04 and concentrated under vacuum. The crude obtained was purified by column chromatography (silica, 100-200 mesh, 40% EtOAc in hexane) to afford 6-chloro-N-(2,5-difluoropyridin-3-yl)-1H-indole-3-sulfonamide 1-1 (0.05 g) as an off-white solid. (1207) Yield: 7%. (1208) Basic LCMS Method 1 (ES ): 342 (M-H)-, 97% purity. (1209) 1H NMR (400 MHz, DMSO-cfe) d 7.25 (dd, J=8.31 , 1.47 Hz, 1 H), 7.54 (s, 1 H), 7.71-7.81 (m, 2H), 7.89 (s, 1 H), 8.16 (d, J=2.93 Hz, 1 H), 10.73 (brs, 1 H), 12.22 (brs, 1 H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1211541-93-3, 5-Fluoro-2-methoxypyridin-3-amine, and friends who are interested can also refer to it.

Reference:
Patent; UCB PHARMA GMBH; PEGURIER, Cecile; PROVINS, Laurent; CARDENAS, Alvaro; LEDECQ, Marie; MUELLER, Christa E.; HOCKEMEYER, Joerg; EL-TAYEB, Ali; BOSHTA, Nader; RASHED, Mahmoud; (165 pag.)WO2019/243303; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 122306-01-8, 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. 122306-01-8, name is (6-Bromopyridin-3-yl)methanol. A new synthetic method of this compound is introduced below.

Step 1A solution of (beta-bromopyridin-3-yl) methanol (2.39 g) described in a reference (Ellingboe, J. W. et al. J. Med. Cheralpha. 1994, 37, 542-550.) in THF (65 mL) was ice-cooled, thionyl chloride (4.64 mL) was added, and the mixture was stirred at 0C for 6 hr. The reaction mixture was concentrated under reduced pressure. Toluene was added and the mixture was concentrated again, and dried under reduced pressure to give 2-bromo-5- (chloromethyl) pyridine hydrochloride (2.54 g) as a brown solid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,122306-01-8, (6-Bromopyridin-3-yl)methanol, and friends who are interested can also refer to it.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; WO2009/119880; (2009); 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.55052-27-2, name is 6-Chloro-1H-pyrrolo[2,3-b]pyridine, molecular formula is C7H5ClN2, molecular weight is 152.581, as common compound, the synthetic route is as follows.Computed Properties of C7H5ClN2

4 g (0.03 mol) of aluminum trichloride, 3 ml of dichloromethane and 3.6 g (0.02 mol), i.e. 2.23 ml, of trichloroacetyl chloride are placed in a round-bottomed flask with a condenser, a magnetic stirrer and a calcium chloride guard tube, and the mixture is stirred at room temperature for 30 minutes. 1.52 g (0.01 mol) of 6-chloro-1H-pyrrolo[2,3-b]pyridine are added portionwise and the mixture is refluxed for 3 hours. While cooling in an ice bath, 50 ml of ice are added to the flask and the mixture is stirred vigorously for 30 minutes. A pasty mass is obtained, which is separated from the aqueous phase by decantation. The product is used directly in the next step.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,55052-27-2, 6-Chloro-1H-pyrrolo[2,3-b]pyridine, and friends who are interested can also refer to it.

Reference:
Patent; SANOFI-AVENTIS; US2005/182062; (2005); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 934279-60-4, Adding some certain compound to certain chemical reactions, such as: 934279-60-4, name is 2-Chloro-5-(trifluoromethyl)nicotinaldehyde,molecular formula is C7H3ClF3NO, 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 934279-60-4.

A mixture of 2-chloro-5-(trifluoromethyl)nicotinaldehyde (33.0 mg, 0.158 mmol), Example 26B (60 mg, 0.143 mmol) and zinc(II) chloride in a sodium acetate/acetic acid buffer in methanol (pH=4, 2 mL) was stirred at ambient temperature for 10 minutes. Sodium cyanoborohydride (23.53 mg, 0.374 mmol) was added and the mixture was stirred for 1 hour until complete as monitored by LC/MS. The solvent was removed and residue was dissolved in dichloromethane (10 mL) and washed with brine, dried over MgSO4, filtered, and concentrated. Purification via chromatography, eluting with ethyl acetate/methanol (10:1) in 377 heptane at a 0-40% gradient provided the intermediate 1184 (2S,3S,4S,5S)-ethyl 3-(tert-butyl)-1-(cyclohexanecarbonyl)-5-(4-fluorophenyl)-4-(((2-methoxy-5-(trifluoromethyl)pyridin-3-yl)methyl)amino)pyrrolidine-2-carboxylate, which was dissolved in methanol (1.5 mL) and 4 M aqueous LiOH (0.5 mL). The mixture was stirred at 50 C. for 3 hours and the pH was adjusted to 4-5 by adding 4 M HCl in dioxane. The resulting mixture was purified via HTP with the trifluoroacetic acid method to provide the title compound (2S,3S,4S,5S)-3-(tert-butyl)-1-(cyclohexanecarbonyl)-5-(4-fluorophenyl)-4-(((2-methoxy-5-(trifluoromethyl)pyridin-3-yl)methyl)amino)pyrrolidine-2-carboxylic acid as trifluoroacetic acid salt. (44 mg, 44.3% yield). 1H NMR (400 MHz, dimethyl sulfoxide-d6) delta ppm 8.32 (s, 1H), 7.62 (s, 2H), 7.56 (d, J=2.4 Hz, 1H), 7.08 (t, J=8.7 Hz, 2H), 5.23 (d, J=7.0 Hz, 1H), 4.47 (d, J=2.5 Hz, 1H), 3.83 (s, 3H), 3.58-3.47 (m, 4H), 2.34 (s, 1H), 2.22 (s, 1H), 1.70-1.04 (m, 10H), 0.97 (s, 9H); MS (ESI+) m/z 580.2 (M+H)+.

According to the analysis of related databases, 934279-60-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AbbVie S.a.r.l.; Galapagos NV; Altenbach, Robert J.; Bogdan, Andrew; Couty, Sylvain; De Lemos, Elsa; Desroy, Nicolas; Duthion, Beranger; Gfesser, Gregory A.; Greszler, Stephen N.; Housseman, Christopher Gaetan; Koenig, John R.; Kym, Philip R.; Liu, Bo; Scanio, Marc J.; Searle, Xenia; Wang, Xueqing; Yeung, Ming C.; Zhao, Gang; (263 pag.)US2018/99931; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 676339-81-4, 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. 676339-81-4, name is 6-(4-Carboxyphenyl)nicotinic acid, molecular formula is C13H9NO4, 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.

(1) Add equimolar amounts of Co (NO3) 2.6H2O (0.145g, 0.5mmol) and H2cpn (0.12g, 0.5mmol) to 12mL dmf solvent, and then stir for 20 minutes;(2) Add the material in step 1 to a 23mL polytetrafluoroethylene reactor, maintain a constant temperature of 130 C for 72 hours under autogenous pressure, and then drop to room temperature at a rate of 5 C / h;(3) The mixture in step 2 is filtered, the crystals are collected, washed with dmf solvent and dried,Purple crystals are obtained.(4) Filter the product, collect the crystals, and dry to obtain purple crystals.According to the calculation of H2cpn, the yield was 48%

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 676339-81-4, 6-(4-Carboxyphenyl)nicotinic acid.

Reference:
Patent; Zhaoqing University; Ma Deyun; Liang Fenglan; Tan Liang; Huang Yewei; Qin Jiayan; Shen Yijun; (7 pag.)CN111057113; (2020); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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. 880870-13-3, name is 5-Bromo-2-chloro-4-methoxypyridine, molecular formula is C6H5BrClNO, 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. Application In Synthesis of 5-Bromo-2-chloro-4-methoxypyridine

A solution of 5-bromo-2-chloro-4-methoxypyridine (5.0 g, 22.48 mmol) in DMF (80 mL) was purged with nitrogen for 15 min. Al this point, Zn(CN)2 (3.96 g, 33.7 mmol) and Pd(Ph3P)4 (2.60 g, 2.25 mmol) were added, successively. The resulting suspension was stirred at 95 0C for 12 h under nitrogen atm. The reaction mixture was cooled to ambient temperature, filtered to remove inorganic solid. The solvent (DMF) was evaporated to provide the crude residue as an oil, which was purified on silica gel and eluted with 0-30% ethyl acetate / hexanes to afford the product. 1H NMR (500 MHz, DMSO-^), delta 8.69 (s, IH), 7.50 (s, IH), 4.04 (s, 3H); LC/MS (M+l)+ – 168.96; tR – 2.05 min

With the rapid development of chemical substances, we look forward to future research findings about 880870-13-3.

Reference:
Patent; MERCK SHARP &; DOHME CORP.; PASTERNAK, Alexander; SHAHRIPOUR, Aurash; TANG, Haifeng; TEUMELSAN, Nardos, H.; YANG, Lihu; ZHU, Yuping; WALSH, Shawn, P.; WO2010/129379; (2010); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 13296-04-3, 4-(Pyridin-4-yl)aniline, 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, 13296-04-3, blongs to pyridine-derivatives compound. COA of Formula: C11H10N2

EXAMPLE 163BA mixture of EXAMPLE 163A (298.8 mg), 4-pyridin-4-yl-phenylamine (124.9 mg), palladium(II) acetate (7 7 mg), 4,5-bis(diphenylphosphino)~9,9-dimethylxanthene (25 6 mg), cesium carbonate (0.46 g), and dioxane (5 mL) were heated in a microwave at 16O0C for 40 minutes The solvent was removed and the residue purified by flash chioniatography on silica gel using 15% methanol/dichloromethane to provide the title compound (141 6 mg, 36%) as a tan powder

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,13296-04-3, its application will become more common.

Reference:
Patent; ABBOTT LABORATORIES; WO2007/140233; (2007); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 1073159-75-7, 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. 1073159-75-7, name is N-(3-(Aminomethyl)pyridin-2-yl)-N-methylmethanesulfonamide acetate. A new synthetic method of this compound is introduced below.

Step 4. Compound C3 (100 mg, 0.24 mmol), B5 (88.5 mg, 0.264 mmol), and diethylamine (DIEA) (0.127 ml, 0.960 mmol) were dissolved in 1,2-dichloroethane (DCE):t-BuOH (1:1 vol:vol) (1.2 mL). The resultant solution was heated at 80 C. for about 20 hours, cooled to 25 C., treated with EtOAc, and washed with water. The organic phase was collected, and the aqueous phase was washed with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated to provide 1 as a sticky residue. MS+ 596.8. 1H NMR (500 MHz, d6-DMSO) delta: 9.50 (s, 1H), 8.41 (m, 1H), 8.22 (s, 1H), 7.61 (m, 2H), 7.35 (m, 3H), 6.99 (d, 2H), 4.76 (d, 2H), 4.47 (m, 1H), 3.14 (s, 3H), 3.11 (s, 3H), 1.33 (s, 9H), 1.21 (d, 3H). The product was used in the preparation of compound 2 in Example 2 below without further purification.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1073159-75-7, N-(3-(Aminomethyl)pyridin-2-yl)-N-methylmethanesulfonamide acetate, and friends who are interested can also refer to it.

Reference:
Patent; Pfizer Inc.; US2009/54395; (2009); 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.936342-91-5, name is 5-Bromo-2-(chloromethyl)pyridine hydrochloride, molecular formula is C6H6BrCl2N, molecular weight is 242.9285, as common compound, the synthetic route is as follows.Formula: C6H6BrCl2N

5-bromo-2-chloromethyl-pyridine (486mg, 2mmol) and thiomorpholine 1,1-dioxide (406mg, 3mmol) was dissolved in N, N- dimethylformamide (10ml) and then potassium carbonate (986mg, 7mmol), the reaction was stirred for 12 hours at room temperature, 100ml of water was added to the reaction mixture was cooled, (100ml * 3) and extracted with ethyl acetate, then with saturated sodium chloride solution (100ml * 2), dried the organic phase was dried over anhydrous magnesium sulfate filtered, and concentrated under reduced pressure to give 1- (5-bromo – pyridin-2-ylmethyl) – (1,1-dioxo – thiomorpholine) – piperazine (499 mg of the , white solid), yield: 81.8percent.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,936342-91-5, 5-Bromo-2-(chloromethyl)pyridine hydrochloride, and friends who are interested can also refer to it.

Reference:
Patent; SHANGHAI CDYMAX PHARMACEUTICALS CO., LTD; An, Xiaoxia; Bie, Pingyan; Liu, Jun; Yang, Wuli; (42 pag.)CN103360407; (2016); B;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem