Month: April 2022

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. 327056-62-2, name is 2-Cyano-5-fluoropyridine, the common compound, a new synthetic route is introduced below. HPLC of Formula: C6H3FN2

Example 32.2-(6-Fluoro-imidazo[l ,5-a]pyridin-l -yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3- cyano-azetidin- 1 -yl)- 1 -methyl-2- xo-ethyl]-amideStep 1(5 -Fluoro-pyridin-2-yl)-meth lamineIn a Parr pressure bottle, 2-cyano-5-fluoropyridine (2.0 g, 16.4 mmol) was dissolved in ethanol (60 ml). Palladium on carbon, 10% Pd (wet) (574 mg, 5.39 mmol) was added followed by cone. HC1 (4.6 ml, 56.0 mmol). The bottle was placed on a Parr hydrogenator and shaken for 3.5 h under a 45 psi hydrogen atmosphere. The reaction mixture was filtered over Celite and rinsed with methanol. The filtrate was concentrated to a light yellow solid. The solid was taken up in dichloromethane, cooled to 0C, and basified with saturated aqueous NaHC03. The aqueous layer was extracted with dichloromethane (3x) and the combined organics were dried over sodium sulfate, filtered and concentrated to give 558 mg (27%) of (5-fluoro-pyridin-2-yl)- methylamine as a yellow oil which was used without further purification.

The synthetic route of 327056-62-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; CHEN, Shaoqing; DE VICENTE FIDALGO, Javier; HAMILTON, Matthew Michael; HERMANN, Johannes Cornelius; KENNEDY-SMITH, Joshua; LI, Hongju; LOVEY, Allen John; LUCAS, Matthew C.; LUK, Kin-Chun Thomas; LYNCH, Stephen M.; O’YANG, Counde; PADILLA, Fernando; SCHOENFELD, Ryan Craig; SIDDURI, Achyutharao; SOTH, Michael; WANG, Ce; WOVKULICH, Peter Michael; ZHANG, Xiaohu; WO2013/30138; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 33252-28-7, 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. 33252-28-7, name is 6-Chloronicotinonitrile, molecular formula is C6H3ClN2, 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.

N-[4-(5-Cyano-2-methoxy-pyridin-3-yl)-benzyl]-2-trifluoromethoxy-benzenesulfonamide To a solution of 4-aminomethylphenylboronic acid hydrochloride (2.0 g, 13.2 mmol) in methanol (20 ml) was added di-tert-butyl dicarbonate (3.16 g, 15.5 mmol) and sodium bicarbonate (3.32 g, 19.8 mmol). The mixture was sonicated for 4 h then concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over anhydrous magnesium sulfate and the solvent evaporated to give (4-bromo-benzyl)-carbamic acid tert-butyl ester (1.8 g, 13.2 mmol, 100%) as a white solid. To 6-chloro-nicotinonitrile (15 g, 0.11 mol) under argon atmosphere was added 25% sodium methoxide in methanol (11.7 g, 0.22 mol) and the mixture heated under reflux for 20 h. The methanol was evaporated and the residue partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried over anhydrous magnesium sulfate and the solvent evaporated to give 6-methoxy-nicotinonitrile (17.0 g, 0.13 mol, 117%) as a white solid. To 6-methoxy-nicotinonitrile (13.2 g, 99 mmol) in acetic acid (32 ml) was added sodium acetate (8.1 g, 99 mmol). The mixture was stirred and a solution of bromine (31.5 g, 197 mmol) in acetic acid (32 ml) added. The mixture was heated to 80 C. for 48 h. The reaction mixture was poured into water and extracted with diethyl ether. The organic phase was washed with 4M aqueous sodium hydroxide solution, 5% sodium thiosulfate solution, dried over anhydrous potassium carbonate and the solvent was evaporated to give 5-bromo-6-methoxy-nicotinonitrile (11.9 g, 56 mmol, 57%). To a solution of 2-methoxy-5-cyanopyridine-3-boronic acid (1.0 g, 4.0 mmol) in 1,2-dimethoxyethane (10 ml) was added (4-bromo-benzyl)-carbamic acid tert-butyl ester (0.42 g, 2.0 mmol), tetrakis(triphenylphosphine)palladium (0) (114 mg, 0.1 mmol) and 2M aqueous sodium carbonate (1 ml, 2.0 mmol). The reaction was heated to 150 C. for 10 min in a microwave over. The mixture was concentrated under reduced pressure and partitioned between ethyl acetate and water. The organic phase was washed with water, then brine, dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified on silica gel eluting with 5:1 heptane/ethyl acetate to give [4-(5-cyano-2-methoxy-pyridin-3-yl)-benzyl]-carbamic acid tert-butyl ester as a white solid (0.5 g, 1.47 mmol, 37%). To a solution of [4-(5-cyano-2-methoxy-pyridin-3-yl)-benzyl]-carbamic acid tert-butyl ester (0.5 g, 1.5 mmol) in dichloromethane (5 ml) at 0 C. was added trifluoroacetic acid (5 ml, 28 mmol). The reaction mixture was stirred for 30 min at 0 C. before the solvent was evaporated and the residue purified on a SCX column (eluted with 2M ammonia in methanol) to give 5-(4-aminomethyl-phenyl)-6-methoxy-nicotinonitrile as a clear glass (0.39 g, 1.6 mmol, 107%). To a solution of 5-(4-aminomethyl-phenyl)-6-methoxy-nicotinonitrile (57.3 mg, 0.24 mmol) in dichloromethane (2 ml) was added triethylamine (73.0 mg, 0.72 mmol) and 2-(trifluoromethoxy)benzenesulfonyl chloride. The reaction mixture was agitated for 20 hours and the solvent evaporated under reduced pressure. The crude product was taken up in dimethyl sulfoxide (1 ml) and purified by preparatory LCMS. The solvent was evaporated under reduced pressure to give the title compound (19.1 mg, 0.04 mmol, 17%). 1H NMR (400 MHz, DMSO-d6): delta 8.68 (d, 1H), 8.47 (t, 1H), 8.15 (d, 1H), 7.90 (m, 1H), 7.73 (m, 1H), 7.45-7.55 (m, 4H), 7.31 (d, 2H), 4.19 (d, 2H), 3.96 (s, 3H) ppm; MS (ESI) m/z: 464.3 [M+H]+.

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 33252-28-7, 6-Chloronicotinonitrile.

Reference:
Patent; N.V. Organon; Pharmacopeia Drug Discovery Inc.; US2007/149577; (2007); A1;,
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. 17570-98-8, name is 2-(Bromoacetyl)pyridine hydrobromide, molecular formula is C7H7Br2NO, 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. category: pyridine-derivatives

Example 8; (S)-(4-Fluoro-phenyl)(3-(4-(pyridin-2-yl)-oxazol-2-yl)-piperidin-l-yl)-methanone; A solution of (S)-I -(4-fluoro-benzoyl)-piperidine-3-carboxylic acid amide (0.2 g, 0.8 mmol), prepared as described in Example l(C), and 2-(bromoacetyl)-pyridine hydrobromide (90 mg, 0.32 mmol) in dry N-methyl-2-pyrrolidinone (2.5 mL) was heated at 1000C for 5 h. The reaction mixture was cooled to room temperature, ethyl acetate was added and the organic layer was washed sequentially with water (twice) and with brine (twice). The organics were dried over sodium sulphate and evaporated under reduced pressure to afford a crude oil that was purified by flash chromatography: after 3 successive column chromatography purifications (silica gel, eluent: DCM/MeOH/NH4OH 98:2:0.2), 18 mg of (S)-(4-Fluoro-phenyl)(3-(4- (pyridin-2-yl)-oxazol-2-yl)-piperidin-l-yl)-methanone were obtained as a brown oil. Yield: 16%; LCMS (RT): 1.99 min (Method H); MS (ES+) gave m/z: 352.2 (MH+). 1H-NMR (DMSO-d6 353K), delta (ppm): 8.57 (ddd, IH) 8.43 (s, IH) 7.77-7.88 (m, 2H) 7.43-7.50 (m, 2H) 7.28-7.33 (m, IH) 7.19-7.27 (m, 2H) 4.21 (dd, IH) 3.78 (dd, IH) 3.46 (dd, IH) 3.13-3.35 (m, 2H) 2.15-2.28 (m, IH) 1.78-2.01 (m, 2H) 1.52-1.70 (m, IH).

With the rapid development of chemical substances, we look forward to future research findings about 17570-98-8.

Reference:
Patent; ADDEX PHARMA S.A.; WO2008/56259; (2008); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 63237-88-7, 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 63237-88-7, name is Pyrazolo[1,5-a]pyridine-2-carboxylic acid. This compound has unique chemical properties. The synthetic route is as follows.

Example 97N-((ls,4s)-4-(2-(4′-(((3S,5R)-3,5-dimethylpiperazin-l-yl)methyl)-3′-hydroxybiphenyl-3- yloxyJ-S-fluoronicotinamidoJcyclohexylJpyrazolo [ 1 ,5-a] pyridine-2-carboxamide To a solution of pyrazolo[l,5-a]pyridine-2-carboxylic acid (30.8 mg, 0.19 mmol) in acetonitrile (3 mL) was added DIPEA (0.066 mL, 0.38 mmol). To this mixture was then added HATU (72.3 mg, 0.19 mmol). The mixture was stirred at RT for 10 min before it was added to a solution of N-((ls,4s)-4-aminocyclohexyl)-2-(4′-(((3S,5R)-3,5-dimethylpiperazin- l-yl)methyl)-3′-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamide, hydrochloride (125 mg, 0.19 mmol) and DIPEA (0.066 mL, 0.38 mmol) in acetonitrile (3 mL). The mixture was stirred at RT overnight. 1 mL water and 1 mL acetic acid was then added to the mixture before being purified using reverse phase preparative HPLC (eluent = TFA(aq)/MeCN). The appropriate fractions were combined and evaporated to give a residue. This was triturated with ether to give the title compound as a solid which was isolated by filtration and dried overnight under vacuum at 400C. Yield: 96 mg 1H NMR (400 MHz, CD3OD) delta 8.48 (d, J = 7.4 Hz, IH), 8.43 (d, J = 7.2 Hz, IH), 8.12 (d, J = 3.1 Hz, IH), 8.06 (dd, J = 7.9, 3.1 Hz, IH), 7.66 (d, J = 9.0 Hz, IH), 7.51 – 7.43 (m, 2H), 7.40 – 7.37 (m, IH), 7.25 – 7.17 (m, 3H), 7.10 – 7.07 (m, 2H), 6.97 – 6.93 (m, 2H), 4.17 – 4.11 (m, IH), 4.07 (s, IH), 4.04 – 3.99 (m, IH), 3.58 – 3.51 (m, 2H), 3.45 – 3.40 (m, 2H), 2.64 (t, J = 12.6 Hz, 2H), 1.92 – 1.70 (m, 8H), 1.31 (d, J = 6.4 Hz, 6H). MS: [M+H]+=692.2 (calc=692.336) (MultiMode+)

According to the analysis of related databases, 63237-88-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2009/144494; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 1083197-78-7, 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. 1083197-78-7, name is 4-(Trifluoromethyl)nicotinaldehyde, molecular formula is C7H4F3NO, 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.

A 50-mL round-bottom flask was charged with 5-cyanopyridin-3-yl (R)-2-methylpiperazine-1-carboxylate (179 mg, 0.727 mmol, 1.20 equiv), 4-(trifluoromethyl)pyridine-3-carbaldehyde (106 mg, 0.606 mmol, 1.00 equiv), triethylamine (184 mg, 1.82 mmol, 3.00 equiv), and 1,2-dichloroethane (10 mL). The mixture was stirred for 1 hour at room temperature prior to addition of sodium triacetoxyborohydride (386 mg, 1.82 mmol, 3.00 equiv). The reaction was stirred overnight at room temperature and quenched with water (30 mL). The resulting solution was extracted with dichloromethane (2*50 mL) and the organic layers were combined, washed with brine (2*30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product (300 mg) was purified by preparative HPLC to afford 94.9 mg (39% yield) of 5-cyanopyridin-3-yl (R)-2-methyl-4-((4-(trifluoromethyl)pyridin-3-yl)methyl)piperazine-1-carboxylate as a yellow oil. 1H NMR (300 MHz, Chloroform-d) delta 9.02 (s, 1H), 8.71-8.73 (m, 2H), 8.64 (s, 1H), 7.84 (s, 1H), 7.54 (d, J=5.1 Hz, 1H), 4.41 (br, 1H), 3.99-4.03 (m, 1H), 3.73 (s, 2H), 3.48 (br, 1H), 2.84-2.87 (m, 1H), 2.69-2.73 (m, 1H), 2.42-2.47 (m, 1H), 2.01-2.31 (m, 1H), 1.41-1.42 (m, 3H). LCMS (ESI, m/z): 406 [M+H]+.

According to the analysis of related databases, 1083197-78-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ABIDE THERAPEUTICS, INC.; GRICE, Cheryl A.; CISAR, Justin S.; DUNCAN, Katharine K.; FENG, Yu; WIENER, John J.M.; WEBER, Olivia D.; (79 pag.)US2018/256566; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 52334-51-7, 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. 52334-51-7, name is 3-Amino-5-methylpyridin-2(1H)-one. A new synthetic method of this compound is introduced below.

Step 1. 6-methyl[1,3]oxazolo[5,4-b]pyridine-2(1H)-thione3-Amino-5-methylpyridin-2-ol (0.21 g, 1.7 mmol) was dissolved in THF (5 mL), and 1,1′-thiocarbonyldiimidazole (0.48 g, 2.7 mmol) was added. The mixture was stirred at RT for 20 min. The reaction was diluted with water, treated with 1N HCl to adjust the pH to the range of 4-5. The product was then extracted with ethyl acetate, the extracts were washed with brine, and dried over sodium sulfate, filtered and concentrated to afford the product, used without further purification in the following step. LCMS (M+H)+: m/z=167.0.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,52334-51-7, 3-Amino-5-methylpyridin-2(1H)-one, and friends who are interested can also refer to it.

Reference:
Patent; Rodgers, James D.; Shepard, Stacey; Arvanitis, Argyrios G.; Wang, Haisheng; Storace, Louis; Folmer, Beverly; Shao, Lixin; Zhu, Wenyu; Glenn, Joseph; US2010/298334; (2010); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 20970-75-6, 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. 20970-75-6, name is 2-Cyano-3-methylpyridine. A new synthetic method of this compound is introduced below.

A mixture of 3-methylpicolinonitrile (2 g, 16.9 mmol, 1.0 eq), NBS (3 g, 16.9 mmol, 1.0 eq) and BPO (41 1 mg, 1.7 mmol, 0.1 eq) in CCU (30 mL) was refluxed and stirred overnight. Then the mixture was cooled to rt and concentrated. The residue was diluted with water (50 mL), extracted with DCM (50 mLx3). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na2S04 and concentrated. The residue was purified on silica gel column (PE/EtOAc = 5/1) to afford 3-(bromomethyl)picolinonitrile as a brown solid (2.1 g, 63%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,20970-75-6, its application will become more common.

Reference:
Patent; LIFESCI PHARMACEUTICALS, INC.; MCDONALD, Andrew; WO2015/103317; (2015); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 799293-73-5, 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 799293-73-5, name is 3-Bromofuro[3,2-c]pyridin-4-amine. This compound has unique chemical properties. The synthetic route is as follows.

General procedure: 4-iodo-1H-indazol-3-amine was replaced by 3-bromofuro[3,2-c]pyridin-4-amine and other raw materials, reagentsand preparation method were identical with those in step 6 of example 1. I-2 as yellow solid was obtained.1H NMR (300 MHz, DMSO-d6) delta (ppm): 5.68 (s, 2H), 7.02 (d, J = 6.0 Hz, 1H), 7.11-7.16 (m, 1H), 7.36-7.42 (m, 2H),7.66-7.71 (m, 1H), 7.76 (dd, J = 9.0, 1.8 Hz, 1H), 7.82-7.85 (m, 3H), 7.92 (d, J = 6.0 Hz, 1H), 8.13-8.19 (m, 3H), 8.34(d, J = 8.4 Hz, 1H), 10.62 (s, 1H).

According to the analysis of related databases, 799293-73-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Shanghai Institute Of Materia Medica Chinese Academy of Sciences; DUAN, Wenhu; DING, Jian; LV, Yongcong; XIE, Hua; (54 pag.)EP3112351; (2017); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 109613-97-0 ,Some common heterocyclic compound, 109613-97-0, molecular formula is C6H7BrN2O, 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.

To an ice-cold solution of 2-bromo-4-methoxypyridin-3-amine (Intermediate 38), (2.74 g) in pyridine (102 mL) was added ethyl chloroformate (1.91 mL) dropwise and then stirred at rt for 45 min. The reaction mixture was cooled in an ice-bath and more ethyl chloroformate (9 mL) added and the mixture left to stir overnight at rt. The reaction mixture was diluted with EtOAc and washed with sat. aq. NaHCO3. The aqueous layer was extracted with EtOAc and the combined organic layers washed with brine, dried over MgSO4, filtered and evaporated under vacuum to give a solid. Product was observed in the aqueous layer by LC-MS, so this was re-extracted with EtOAc (3*) and evaporated under vacuum to give a solid which was combined with the previous solid, dissolved in DCM and purified by column chromatography (normal phase, 50 g, Biotage SNAP cartridge KP-Sil, 50 mL/min, gradient 10-70% EtOAc in n-hexane) to give the desired product (2.35 g). LCMS: m/z 275.43 [M+H]+. 1H NMR (400 MHz, CDCl3) ppm 1.32 (t, J=7.1 Hz, 3H) 3.93 (s, 3H) 4.24 (q, J=7.1 Hz, 2H) 6.06 (br. s., 1H) 6.86 (d, J=5.6 Hz, 1H) 8.19 (d, J=5.6 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. 109613-97-0, 2-Bromo-4-methoxypyridin-3-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; EISAI R&D MANAGEMENT CO., LTD.; PAYNE, Andrew; CASTRO PINEIRO, Jose Luis; BIRCH, Louise Michelle; KHAN, Afzal; BRAUNTON, Alan James; KITULAGODA, James Edward; SOEJIMA, Motohiro; WO2015/49574; (2015); 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.52311-50-9, name is 2-Chloro-4-ethoxypyridine, molecular formula is C7H8ClNO, molecular weight is 157.6, as common compound, the synthetic route is as follows.Safety of 2-Chloro-4-ethoxypyridine

A mixture of 2-chloro-4-ethoxypyridine (200 mg, 1.3 mmol), cyclohexanamine (152 mg, 1.47 mmol), Pd2(dba)3 (12 mg, 0.013 mmol), BINAP (40 mg, 0.064 mmol), NaOt-Bu (244 mg, 2.53 mmol) and toluene (5 mL) in a 50 mL round bottom flask fitted with a reflux condenser was heated at 100 C. for 4 h under a N2 atmosphere. The crude reaction mixture was concentrated to dryness to give the title compound as a red oil that was used in subsequent reactions without further purification.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,52311-50-9, 2-Chloro-4-ethoxypyridine, and friends who are interested can also refer to it.

Reference:
Patent; Janssen Pharmaceutica NV; Goldberg, Steven; McClure, Kelly; Tanis, Virginia M.; Fennema, Elizabeth G.; Lebsack, Alec D.; Martin, Connor L.; Venkatesan, Hariharan; Xue, Xiaohua; Woods, Craig R.; (531 pag.)US2017/313691; (2017); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem