Day: March 22, 2022

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

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 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.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

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

Electric Literature of 1030626-87-9, 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 1030626-87-9 as follows.

A.6 (5-Chloro-fl, 2, 4]triazolo[l, 5-a]pyridin-8-yl)-[4-(4-methyl-piperazin-l-yl)-phenyl] -amine[0333] A solution of 8-bromo-5-chloro-[l,2,4]triazolo[l,5-a]pyridine (100 mg, 0.43 mmol), A-(4-methyl-piperazin- 1 -yl)-phenylamine (91 mg, 0.47 mmol), sodium-tert-butoxide (58 mg, 0.6 mmol), tris(dibenzylideneacetone)dipalladium (0) (39 mg, 40 mumol) and Xantphos (50 mg, 90 mumol) in dioxane is degassed for one minute by nitrogen bubbling and irradiated in a sealed tube in a microwave (CEM Explorer) under a nitrogen atmosphere for 45 minutes at 110 0C. After addition of dichloromethane the suspension is filtered through a plug of silica and the filtrate evaporated and stripped twice with dichloromethane. The residue is purified by flash chromatography (silica gel, dichloromethane/7N NH3 in methanol 95:5) affording the title compound (95 mg) as a foam.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1030626-87-9, its application will become more common.

Reference:
Patent; GALAPAGOS N.V.; BURRITT, Andrew; WO2008/65198; (2008); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 22282-70-8 ,Some common heterocyclic compound, 22282-70-8, molecular formula is C5H3FIN, 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.

Example 216A 2-Fluoro-4-vinylpyridine A mixture of 2-fluoro-4-iodopyridine (2.23 g, 10.0 mmol), tributyl vinyl tin (3.8 g, 12 mmol), and Pd2Cl2 (PPh3)2 (703 mg, 1.0 mmol) in dioxane (20 mL) was heated under nitrogen at 80 C. overnight. After cooled, ethyl acetate (40 ml) and saturated KF aqueous solution were added to the reaction mixture. The mixture was stirred for 30 min. The organic layer was separated and washed with water, dried (MgSO4), and concentrated. The resulting residue was purified by flash column chromatography eluding with hexane/ethyl acetate (20:1) to provide the title compound (463 mg, 38%). 1H-NMR (500 MHz, CDCl3) delta ppm 5.55 (d, J=10.92 Hz, 1H) 5.99 (d, J=17.47 Hz, 1H) 6.67 (dd, J=17.47, 10.61 Hz, 1H) 6.88 (m, 1H) 7.17 (dt, J=5.30, 1.56 Hz, 1H) 8.16 (d, J=5.30 Hz, 1H).

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. 22282-70-8, 2-Fluoro-4-iodopyridine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Li, Qun; Woods, Keith W.; Zhu, Gui-Dong; Fischer, John P.; Gong, Jianchun; Li, Tongmei; Gandhi, Virajkumar; Thomas, Sheela A.; Packard, Garrick K.; Song, Xiaohong; Abrams, Jason N.; Diebold, Robert B.; Dinges, Jurgen; Hutchins, Charles W.; Stoll, Vincent S.; Rosenberg, Saul H.; Giranda, Vincent L.; US2003/199511; (2003); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 628691-93-0, 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 628691-93-0, name is 2-Chloro-3-fluoroisonicotinic acid. This compound has unique chemical properties. The synthetic route is as follows.

Step 1. 3-fluoro-2-vinylisonicotinic acidA solution of 2-chloro-3-fluoroisonicotinic acid (1.50 g, 8.55 mmol, Matrix), dibutyl vinylboronate (2.82 mL, 12.8 mmol, Aldrich), and potassium carbonate (1.42 g, 10.25 mmol) in N,N-dimethylacetamide (9 mL) and water (3 mL) was degassed by bubbling a stream of nitrogen through the solution for 20 minutes.Tetrakis(triphenylphosphine)palladium(0) (0.59 g, 0.51 mmol) was added and the mixture was similarly degassed for a further 10 minutes. The reaction vessel was sealed and heated in the microwave for 25 minutes at 135 C. The reaction mixture was filtered and purified using preparative HPLC (UV-detection) eluting with a gradient ofH20/MeCN containing 0.1% TFA. This reaction was run again on the same scale and the product of both runs were pooled. Solvent was removed from the eluent containing desired product in vacuo (1.3 g, 46%). 1H NMR (300 MHz, CD3OD): delta 8.45 (d, 1H), 7.69 (dd, 1H), 7.07 (ddd, 1H), 6.44 (dd, 1H), 5.65 (dd, 1H); 19F NMR (282 MHz, CD3OD): delta -129.64 (d, IF); LCMS (M+H)+: 167.9.

According to the analysis of related databases, 628691-93-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; INCYTE CORPORATION; RODGERS, James D.; SHEPARD, Stacey; ZHU, Wenyu; SHAO, Lixin; GLENN, Joseph; WO2012/68450; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 96630-88-5, Adding some certain compound to certain chemical reactions, such as: 96630-88-5, name is 4-Chloro-3-hydroxypyridine,molecular formula is C5H4ClNO, 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 96630-88-5.

Step A: Preparation of 4-Chloro-3-methoxypyridine. To a cold solution of 4-chloropyridin-3-ol (200 mg, 1.544 mmol), triphenylphosphine (0.810 g, 3.088 mmol), and MeOH (0.125 mL, 3.088 mmol) in THF (5 mL) was slowly added diisopropyl azodicarboxylate (0.610 mL, 3.088 mmol). The reaction was stirred at room temperature for 1 h. The mixture was concentrated under reduced pressure and the residue was triturated with EtOAc to precipitate triphenylphosphine oxide. The solid was removed by filtration and the filtrate was concentrated under reduced pressure and purified by column chromatography to give the title compound (89.4 mg, 0.623 mmol, 40.3%) (purity was about 58 wt%) as a brown oil. LCMS m/z = 144.2 [M+H]+; lU NMR (500 MHz, CDC13) delta ppm 4.00 (s, 3H), 7.32 (d, J = 5.04 Hz, 1H), 8.17 (d, J = 4.41 Hz, 1H), 8.30 (s, 1H).

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. 96630-88-5, 4-Chloro-3-hydroxypyridine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ARENA PHARMACEUTICALS, INC.; JONES, Robert, M.; BUZARD, Daniel, J.; HAN, Sangdon; KIM, Sun, Hee; LEHMANN, Juerg; WO2012/170702; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 147071-00-9, 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 147071-00-9 as follows.

To a stirred solution of methyl 1 AY-pyrrolo[2,3-c]pyridine-5-carboxylate (15.Og, 85.1 mmol) in DMF (120 mL) at 1O0C under a nitrogen atmosphere was added sodium hydride (3.75 g, 60% in mineral oil, 93.7 mmol) in three portions over 5 min. The slurry became a homogeneous solution. After 130 min at 10 0C, 4- fluorobenzyl bromide (0.6Og, 2.89 mmol) was added at such a rate that the temperature did not exceed 15 0C. The resulting mixture was stirred for 2.5 hours at ambient temperature, quenched with water (12OmL), and extracted with ethyl acetate (3 x 30 mL). The combined organic extracts were washed with water (2 x 30 mL), dried over sodium sulfate, filtered, concentrated under reduced pressure and purified by flash chromatography. Elution with hexane:ethyl acetate (2:1) provided the title compound as a white solid (21.3 g, 88% yield). 1H NMR (300 MHz, DMSO-D6) delta, ppm: 3.84 (s, 3H), 5.59 (s, 2H), 6.73 (d, J=2.Q Hz, 1H), 7.15 (t, J=8.9 Hz, 2H), 7.34 (dd, J=8.3, 5.7 Hz, 2H), 7.87 (d, J=2.8 Hz, 1 H), 8.3 (s, 1 H), 8.97 (s, 1 H). LCMS (APCi, M+H+): 285.3.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,147071-00-9, its application will become more common.

Reference:
Patent; PFIZER INC.; WO2006/27694; (2006); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem