Category: imidazoles-derivatives

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. 2302-25-2 name is 4-Bromo-1H-imidazole, This 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. 2302-25-2

1 (300 mg, 2.05 mmol), DCM (10 mL), TEA (3.0 eq), (Boc)20 (1.2 eq), 0C for 10 min; gradually warmed to RT for 10 min and stirred. After 16 h, a non-polar product was observed by TLC. The reaction was quenched with water and extracted with EtOAc (2X20 mL). The combined organic layer was washed with water and dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to afford the crude which was purified by silica gel column chromatography [using 100-200 mesh, eluting with 20% EtOAc-hexane] to afford 320 mg of 2 as white solid. Repeat preparation with 1 (1 g, 6.83 mmol), DCM (20 mL), TEA (3.0 eq), (Boc)20 (1.2 eq), 0 oC-RT. After 16 h, one non-polar product was observed by TLC. The reaction mixture was quenched with water and extracted with EtOAc (2X30 mL). The combined organic layer was washed with water and dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to afford the crude which was purified by silica gel column chromatography [using 100-200 mesh, eluting with 20% EtOAc-hexane] to afford 1.2 g of 2 as white solid.

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

Reference:
Patent; UNITHER VIROLOGY, LLC; RAMSTEDT, Urban; WARFIELD, Kelly Lyn; TRESTON, Anthony; (147 pag.)WO2016/73652; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

71759-89-2, Name is 5-Iodo-1H-imidazole, 71759-89-2, belongs to imidazoles-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows.

Et3N (0.59 mL, 4.25 mmol) was added to a solution of 4-iodoimidazole [71759-89-2] (750 mg, 3.87 mmol) in DCM (30 mL). The reaction mixture was stirred at room temperature for 5 min and trytil chloride (1.19 g, 4.25 mmol) was added. The reaction mixture was stirred at 40 C for 16 h. The reaction mixture was diluted with NaHCCh (sat., aq.) and extracted with DCM. The organic layer was dried (MgS04), filtered and the solvent were evaporated in vacuo. The crude mixture was purified by flash column chromatography (silica, heptane/EtOAc, gradient from 100:0 to 60:40) to afford 1-169 (976 mg, 58%).

Statistics shows that 5-Iodo-1H-imidazole is playing an increasingly important role. we look forward to future research findings about 71759-89-2.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; BARTOLOME-NEBREDA, Jose Manuel; TRABANCO-SUAREZ, Andres, Avelino; TRESADERN, Gary John; MARTINEZ LAMENCA, Carolina; LEENAERTS, Joseph Elisabeth; OEHLRICH, Daniel; BUIJNSTERS, Peter Jacobus Johannes Antonius; VELTER, Adriana, Ingrid; VAN ROOSBROECK, Yves, Emiel, Maria; (171 pag.)WO2019/243535; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

A common compound: 26663-77-4, name is Methyl benzimidazole-5-carboxylate, belongs to imidazoles-derivatives compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 26663-77-4

tert-butyl-2-chloro-4-fluorobenzoate (200 mg, 0.867 mmol), methyl lH-benzimidazole-5- carboxylate (214 mg, 1.214 mmol) and potassium carbonate (359 mg, 2.60 mmol) in dry acetonitrile (12 mL) was stirred at 85C for 6 h. The reaction mixture was cooled to RT and the solid was filtered and washed with EtOAc. The filtrate was concentrated and purified by flash chromatography (ISCO CombiFlash system, 80g Silica gel column, 0-60% EtOAc in hexane as as eluting solvent) to afford the product as a mixture of two regioisomers. Further separation of this mixture of products by SFC technique on chiral AD-H column and using 55% MeOH/C02 as mobile phase yielded compound 18A-a, methyl l-(4-(tert-butoxycarbonyl)-3-chlorophenyl)- lH-benzo[d]imidazole-6-carboxylate, and compound 18A-b, methyl l-(4-(tert-butoxycarbonyl)- 3- chlorophenyl)-lH-benzo[d]imidazole-5-carboxylate. For compound 18A-a: methyl 1 -(4-(tert-butoxycarbonvD-3 -chlorophenvD- 1 H- benzo[dlimidazole-6-carboxylate (M+H) calc. = 387.10; found = 387.15. 1H NMR (500 MHz, CD3OD): delta 8.70 (s, br, 1 H); 8.30 (s, br, 1 H); 8.08 (dd, J = 1.5 Hz, J = 8.5 Hz, 1 H); 8.01 (d, J = 8.5 Hz,l H); 7.89 (d, J = 2.5 Hz,l H); 7.86 (d, J = 8.5 Hz, 1 H); 7.74 (dd, J = 2.0 Hz, J = 8.5 Hz, 1 H); 3.95 (s, 3H); 1.66 (s, 9H) For compound 18A-b: methyl 1 -(4-(tert-butoxycarbonyl)-3 -chlorophenyD- 1 H- benzo[dlimidazole-5-carboxylate (M+H) calc. = 387.10; found = 387.15. 1H NMR (500 MHz, CD3OD): delta 8.56 (s, br, 1 H); 8.47 (s, br, 1 H); 8.12 (dd, J = 1.5 Hz, J = 8.5 Hz, 1 H); 8.10 (d, J = 8.5 Hz,l H); 7.89 (d, J = 2.0 Hz,l H); 7.76 (d, J = 8.5 Hz, 1 H); 7.73 (dd, J = 2.0 Hz, J = 8.5 Hz, 1 H); 3.97 (s, 3H); 1.65 (s, 9H) Additional NMR studies (NOE) confirmed the structure assignments of the two products.

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, 26663-77-4, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MOCHIDA PHARMACEUTICAL CO., LTD.; ZHANG, Ting; CHEN, Yi-Heng; GUO, Liangqin; HRUZA, Alan; JIAN, Tianying; LI, Bing; MENG, Dongfang; PARKER, Dann, L., Jr.; SHERER, Edward, C.; WOOD, Harold, B.; SAKURADA, Isao; (130 pag.)WO2016/94260; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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 7098-07-9 as follows. 7098-07-9

General procedure: To a vigorously stirred solution of imidazole derivatives (23.39mmol) in dry toluene (10mL) at room temperature was added the solution of chloromethyl-salicylaldehydes 2a, b (19.50mmol) in dry toluene (10mL), drop-wise, under nitrogen atmosphere. The resulting solution was further stirred at 60¡ãC for 24h. The product separated out was washed twice with toluene (2¡Á5mL) and several times with ether (5¡Á10mL), to remove the unreacted materials, and dried under vacuum to give pale yellow solid which used for the following preparations without further purification. Samples of the products were nevertheless isolated and fully characterized, as described below.

According to the analysis of related databases, 7098-07-9, the application of this compound in the production field has become more and more popular.

Reference:
Article; Elshaarawy, Reda F.M.; Janiak, Christoph; European Journal of Medicinal Chemistry; vol. 75; (2014); p. 31 – 42;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

288-32-4, 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. 288-32-4 name is 1H-Imidazole, This 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.

To a solution of N-H heterocycle (1 mmol) and aryl halide (2 mmol) in toluene were added catalyst (0.07 g, 0.016 mmol) and K2CO3 (276 g, 2 mmol) and the mixture stirred at 110 C for the specified time. The progress of the reaction was monitored by TLC. The reaction mixture allowed cooling to room temperature and ethyl acetate (25 mL) was added and the mixture stirred for 15 min to ensure product removal from catalyst. Then the catalyst was filtered, washed with ethyl acetate (2 9 25 mL). The organic layer was evaporated under vacuum on a rotary evaporator and the crude product was obtained. Further purification was achieved by column chromatography using ethyl acetate/n-hexane gradient. Structural assignments of the products are based on their 1H NMR and melting point.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1H-Imidazole, and friends who are interested can also refer to it.

Reference:
Article; Hosseinzadeh, Rahman; Aghili, Nora; Tajbakhsh, Mahmood; Catalysis Letters; vol. 146; 1; (2016); p. 193 – 203;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

312-73-2, name is 2-(Trifluoromethyl)-1H-benzo[d]imidazole, belongs to imidazoles-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. 312-73-2

2-Trifluoromethyl-1H-benzimidazole 2 (1.35 g, 10 mmol)Was added to a round bottom flask equipped with 15 mL of acetone,After stirring, an alkene (alkyne) propyl bromide (0.87 mL, 10 mmol)And K2CO3 (2.07 g, 15 mmol),Heating reflux,TCL detection,After the reaction is complete,Cooling cooling,The solid was removed by filtration,The solid was washed with dichloromethane,The acetone solution was concentrated and mixed with the dichloromethane solution,Washed with H2O (15 mL x 3),The organic phase was dried over anhydrous MgSO4,Filtered and concentrated to get crude,To obtain 2.06 g of 1-propargyl-2-trifluoromethyl-1H-benzimidazole (3)Yield 91.96%.

Statistics shows that 312-73-2 is playing an increasingly important role. we look forward to future research findings about 2-(Trifluoromethyl)-1H-benzo[d]imidazole.

Reference:
Patent; Zhejiang University of Technology; Wang Yuguang; He Rongjun; Dong Huichan; Zhu Bingchun; (14 pag.)CN104496975; (2017); B;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

705-09-9, Adding a certain compound to certain chemical reactions, such as: 705-09-9, name is 2-(Difluoromethyl)-1H-benzo[d]imidazole, belongs to imidazoles-derivatives compound, 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 705-09-9.

Step 2: NaH (60%, l . lg, 45.8mmol, 1.5eq) was added protion-wise to a solution of compound Id (3.4g, 20.1mmol, l .leq) in DMF(50mL) at 0C and the mixture was stirred at r.t for 45min. Compound 5a (5.0g, 18.3mmol, leq) was added to the mixture. The mixture was stirred at r.t over weekend. Water was added and the mixture was extracted with ethyl acetate, the organic layer was washed with water for 3 times, dried, concentrated and purified by column chromatography to give 5b (3.4g, yield: 45.8%) as a white solid.’H NMR(CDC13, 300MHZ, ppm): delta 10.23(s, 1H), 7.72(d, 1H), 7.54(d, 1H)ES-MS m/z: 321(M+H+).

According to the analysis of related databases, 705-09-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; TYROGENEX, INC.; LIANG, Congxin; WO2011/41399; (2011); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

71759-89-2, Name is 5-Iodo-1H-imidazole, 71759-89-2, belongs to imidazoles-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows.

Step D 1-Trityl-4-iodoimidazole Trityl chloride (3.8 g, 13.6 mmol) was added to a cooled (0 C.) solution of 4-iodoimidazole (2.25 g, 11.6 mmol) and triethylamine (2 ml, 14.3 mmol) in methylene chloride (25 ml). After stirring for 30 min the reaction mixture was warmed to room temperature and stirred ther for 2 h. The reaction mixture was washed well with water and saturated NaHCO3 then dried (Na2 SO4). Concentration gave the product as a white solid. 1 H NMR (CDCl3) d 6.92 (s, 1 H), 7.08-7.20 (m, 6 H), 7.28-7.40 (m, 10 H).

Statistics shows that 5-Iodo-1H-imidazole is playing an increasingly important role. we look forward to future research findings about 71759-89-2.

Reference:
Patent; Merck & Co., Inc.; US5932606; (1999); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

41716-18-1, A common compound: 41716-18-1, name is 1-Methyl-1H-imidazole-4-carboxylic acid, belongs to imidazoles-derivatives compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

Example 141-Methyl-N-[3-methyl-5-(trifluoromethoxy)benzyl]-N-(tetrahydro-2H-thiopyran-4-yl)-1H-imidiazole-4-carboxamideA mixture of N-[3-methyl-5-(trifluoromethoxy)benzyl]tetrahydro-2H-thiopyran-4-amine (830 mg), 1-methyl-1H-imidazole-4-carboxylic acid (380 mg), EDC.HCl (860 mg), HOBt (460 mg), dimethylformamide (20 mL) and triethylamine (0.94 mL) was stirred overnight at room temperature.The solvents were distilled off under reduced pressure and extraction was conducted with ethyl acetate; the organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated saline and dried over anhydrous magnesium sulfate.After filtering off the desiccant, the solvent was concenrated.The residue was purified by column chromatography (NH silica gel cartridge; hexane/ethyl acetate=90:10 to 10:90) to give the titled compound (810 mg).

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, 1-Methyl-1H-imidazole-4-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; TAISHO PHARMACEUTICAL CO., LTD.; US2012/10414; (2012); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

71759-87-0, 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. 71759-87-0, name is 4-Iodo-1-methyl-1H-imidazole, A new synthetic method of this compound is introduced below.

[0395] Under inert atmosphere, a mixture of Example 43f (100 mg, 0.27 mmol), Example 43g (144 mg, 0.69 mmol), Pd(PPh3)2Cl2 (19 mg, 0.027 mmol), triethylamine (272 mg, 2.7 mmol) and Cul (5.2 mg, 0.027 mmol) in 10 mL of DMF was stirred at 80C for 2 hours. The mixture was filtered and the filtrate was concentrated. The residue was purified by Prep-HPLC (by Ultimate XB-C18, 50 x 250 mm, 10 mum,, speed: 80 mL/min, eluent: H20/CH3CN = from 80/20 to 20/80 over 50 min)to give the desired product (17 mg, yield: 14.2%) as a yellow solid. LCMS [M+l] +=444.0 [0396] 1H NMR (400 MHz, DMSO-d6) delta 10.85 (s, 1H), 8.85 (s, 1H), 8.19 (d, J= 8.3 Hz, 1H), 8.02 (t, J= 8.0 Hz, 1H), 7.89 (d, J= 7.6 Hz, 1H), 7.77 (d, J= 7.1Hz, 1H), 7.68 (s, 1H), 7.57 (s, 1H), 7.38 (d, J=11.1Hz, 1H), 5.72 – 5.61 (m, 1H), 3.67 (s, 3H), 3.32 (s, 3H), 1.42 (d, J= 6.6 Hz, 6H).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; FRONTHERA U.S. PHARMACEUTICALS LLC; JIN, Bohan; DONG, Qing; HUNG, Gene; (227 pag.)WO2018/151830; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem