Category: imidazoles-derivatives

Some common heterocyclic compound, 36947-69-0, name is 2-(tert-Butyl)-1H-imidazole, molecular formula is C7H12N2, 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. SDS of cas: 36947-69-0

Step c: 2-tert-butyl-N,N-dimethyl- 1H- imidazole- 1 -sulfonamide[0465] 2-tert-Butyl-lH- imidazole (0.5 g, 4.03 mmol) was added to a suspension of 60% sodium hydride (0.5 g, 12.1 mmol) in DMF (6.0 mL) at 0C and the mixture was stirred for 0.5 h. Then N,N-dimethylsulfamoyl chloride (0.7 g, 4.84 mmol) was added dropwise and the reaction mixture was stirred at room temperature for 2 h. Saturated NH4CI solution was added and the resulting mixture was extracted with ethyl acetate. The combined extracts were washed with brine, dried over anhydrous Na2S04 and concentrated. The residue was purified by flash column chromatography on silica gel (DCM/MeOH = 20: 1 to 5: 1) to afford 0.8 g of the title compound as a white solid (86%> yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 36947-69-0, its application will become more common.

Reference:
Patent; ZENOBIA THERAPEUTICS, INC.; BOUNAUD, Pierre-Yves; NIENABER, Vicki; STEENSMA, Ruo, W.; LOWE, John, A., III; WO2012/178015; (2012); A2;,
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 3034-38-6 as follows. Recommanded Product: 5-Nitro-1H-imidazole

General procedure: A mixture of 1.6 mmol of C-nitro-NH-azole (1a-e), 2.6 mmol of arylboronic acid (2a-n), 1.6 mmol of sodium hydroxide, 0.2 mmol of CuCl2 and methanol (15 mL) was refluxed while air was bubbled through the reaction mixture. After completion of the reaction, determined on the basis of TLC analysis, the solvent was removed under reduced pressure using a rotary evaporator. The obtained crude product was purified by silica gel column chromatography with 5:95 v/v MeOH/CHCl3 as an eluent to give corresponding N-aryl-C-nitroazole. The product was crystallized from methanol/water.

According to the analysis of related databases, 3034-38-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Kurpet, Marta K.; Dabrowska, Aleksandra; Jarosz, Malgorzata M.; Kajewska-Kania, Katarzyna; Kuznik, Nikodem; Suwinski, Jerzy W.; Beilstein Journal of Organic Chemistry; vol. 9; (2013); p. 1517 – 1525;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 96797-15-8, 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. 96797-15-8 name is 4-Iodo-1-trityl-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.

[270] To a solution of (2-forrnylphenyl)boronic acid (2.0 g, 13.3 rnrnol) in a rnixed solvent of N,N- dirnethylforrnarnide (DMF) (60 rnL) and water (12 rnL) was successively added 4-iodo-1- trityl-1H-irnidazole (6.1 g, 14.0 rnrnol), and potassiurn phosphate (5.6 g, 26.6 rnrnol). After degassing with nitrogen, the resulted rnixture was added tetrakis(triphenylphosphine)palladiurn(0) (Pd(PPh3)4) (300 rng, 0.26 rnrnol). The resulted rnixture was degassed with nitrogen and stirred at 90C for overnight under nitrogen. And then the rnixture was cooled down to roorn ternperature and filtered, the filtrate was added water (60 rnL), extracted with ethyl acetate (100 rnLx2). The cornbined organic phase was washed with brine (25 rnL), dried over sodiurn sulfate, filtered and concentrated. The residue was purifiedby colurnn chrornatography on silica gel (petroleurn ether: ethyl acetate= 6:1) to afford cornpound 1.1 (3.3 g, yield: 60%) as a white solid.[271] rn/z: [M+H]415

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

Reference:
Patent; SHANGHAI DE NOVO PHARMATECH CO.,LTD.; LI, Qun; GAO, Daxin; (158 pag.)WO2016/131380; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1632-83-3, name is 1-Methylbenzimidazole, 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. SDS of cas: 1632-83-3

In an oven dried nitrogen purged 3 neck 100 mL round bottom flask, 1.00 g (7.57 mmol) of 1 -methylbenzimidazole in 20 mL of dry tetrahydrofuran is cooled to -78C. 10.69 mL (18.17 mmol) of 1.7 M t-butyllithium in hexanes is added and the reaction mixture is stirred at -780C. for 1 h. 2.55 g (11.36 mmol) of NIS in 20 mL of dry tetrahydrofuran is added. Reaction is removed from bath and stirred at room temperature for 1 hour, quenched with saturated aqueous solution of ammonium chloride, and diluted with dichloromethane. The layers are separated, the aqueous is extracted 3X100 mL dichloromethane, dried (MgSO4), and concentrated. The crude mixture is purified by EPO chromatography using hexanes:ethyl acetate as a solvent system. The product containing fractions are combined to obtain 0.400 g of the title compound, 21% yield. MS, ES+ = 259.0 (M+l); 1H NMR (DMSO-d6) 57.580-7.552 (m, 2H); 7.228-7.129 (m, 2H); 3.750 (s, 3H) ppm.

The synthetic route of 1632-83-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; WO2006/107784; (2006); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 1074-59-5, name is 3-(1H-Imidazol-4-yl)propanoic acid, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C6H8N2O2

3-(1-Triphenylmethyl-4-imidazolyl)propionic acid 3-(4-Imidazolyl)propionic acid (1.0 g, 7.1 mmol) was suspended in a mixture of dichloro-methane (5 ml) and acetonitrile (25 ml). Trimethylsilyl chloride (781 mg, 7.2 mmol) was added and the mixture refluxed for 4 hours. Triethylamine (1 ml) was added, and refluxing continued for 15 minutes. Cooled, triethylamine (1 ml) added followed by chlorotriphenylmethane (1.99 g, 7.1 mmol) in dichloromethane (10 ml), and the mixture stirred at ambient temperature for 2 hours. MeOH (20 ml) was added, the mixture stirred for 30 minutes, then evaporated to dryness. Water (50 ml) was added to the residue, and the pH adjusted to 8-8.5 with triethylamine. The precipitate was filtered off, washed with diethyl ether, and dried to give the desired product (2.25 g). MS (ESP): 383 (MH+) for C25H22N2O2 NMR (DMSO-d6) delta: 2.48 (t, 2H); 2.77 (t, 2H); 6.65 (s, 1H); 7.08 (d, 6H); 7.29 (s, 1H); 7.36 (m, 9H); 12.10 (br, 1H).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 1074-59-5.

Reference:
Patent; Syngenta Limited; US2003/144263; (2003); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 18075-64-4,Some common heterocyclic compound, 18075-64-4, name is 1-Phenyl-1H-imidazole-4-carboxylic acid, molecular formula is C10H8N2O2, 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 185 Synthesis of 1-Phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide DIPEA (170 mg, 1.3 mmol) was added to a stirred solution of 1-phenyl-1H-imidazole-4-carboxylic acid (55 mg, 0.29 mmol) in DMF (5 mL) followed by HOBt (43 mg, 0.32 mmol) and EDCI (140 mg, 0.7 mmol). After 2 minutes of stirring, 2-amino-1-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (98.5 mg, 0.32 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with cold water, extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure. The residue obtained was purified by washing with ether to afford 63.5 mg (49.6% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 441.17. 1H NMR (300 MHz, DMSO-d6): delta 8.4 (s, 1H), 8.3 (s, 1H), 8.08 (t, 1H), 7.8 (d, 2H), 7.6 (t, 2H), 7.44 (t, 1H), 7.3 (m, 1H), 6.84 (m, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 4.0 (bs, 1H), 3.8 (bs, 1H), 3.7 (bs, 2H), 3.5 (bs, 1H), 2.1 (t, 2H), 1.8 (d, 2H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Phenyl-1H-imidazole-4-carboxylic acid, its application will become more common.

Reference:
Patent; Forest Laboratories Holdings Limited; US2009/239810; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 144689-93-0, 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 144689-93-0 as follows.

First, alkyl 4-(1-hydroxy-1-methylethyl)-2-propyl imidazole-5-carboxylate (20.0 g, 83.2 mmol) and sodium hydroxide powder (6.6 g, 165.0 mmol) were dissolved in 100 ml of acetone and distilled water, and the mixture was stirred and refluxed at 110 C for 3 hours. After cooling to room temperature, the acetone was removed by concentration under reduced pressure. The distilled water layer was titrated with 5N HCl acid at 0C. The solids were filtered off and dried to give compound 2 (14.46 g, 82%).

According to the analysis of related databases, 144689-93-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CTC Bio Co.,Ltd; Oh, Chang Hyun; Kim, Jung Hoon; Yu, Sung Won; Kim, Hyun Ir; (9 pag.)KR101628758; (2016); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

623577-60-6, name is 4-Bromo-1-isopropyl-1H-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. Product Details of 623577-60-6

A mixture of methyl 5-methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyridine-2- carboxylate (300 mg, 1.08 mmol), 4-bromo-l -(propan-2 -yl)-lH-imidazole (307.0 mg, 1.62 mmol), Pd(PPh3)4 (250.2 mg, 0.22 mmol), K2CO3 (448.8 mg, 3.25 mmol) in dioxane (5 ml) was stirred at 100 C under nitrogen atmosphere overnight. The resulting mixture was 39 concentrated under vacuum and purified by reverse phase flash chromatography with 0-37% MeCN/fhO to afford compound 23-a (180 mg, 64.12%) as yellow oil.

The synthetic route of 623577-60-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ENANTA PHARMACEUTICALS, INC.; WANG, Guoqiang; SHEN, Ruichao; GRANGER, Brett; HE, Jing; XING, Xuechao; HE, Yong; LONG, Jiang; MA, Jun; WANG, Bin; OR, Yat, Sun; (99 pag.)WO2019/213244; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 540516-28-7, 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. 540516-28-7, name is 2-(Hydroxymethyl)-5-bromobenzimidazole belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

N-Methyl-2-methanol 5-bromobenzimidazole 50 was prepared according to the procedure by Gonzlez-Chvez et al. [28]. A solution of 5-bromo-(1H-benzimidazole-2-yl)-methanol 28 (0.60 g, 2.60 mmol), and sodium hydroxide (0.10 g, 2.60 mmol) were stirred in dry acetone (10 mL) for 30 min. Then, iodomethane (0.37 g, 2.60 mmol) was added and the mixture was stirred for 24 h. The reaction mixture was concentrated to a quarter and then poured into ice-cold water. The solid was filtered and washed with 50% HCl. The solid was washed with water (100 mL) and purified by column chromatography (9:1 chloroform/ethanol) to give the desired product (50) as a bright yellow crystals Yield 16%.

The synthetic route of 2-(Hydroxymethyl)-5-bromobenzimidazole has been constantly updated, and we look forward to future research findings.

Reference:
Article; Alasmary, Fatmah A.S.; Snelling, Anna M.; Zain, Mohammed E.; Alafeefy, Ahmed M.; Awaad, Amani S.; Karodia, Nazira; Molecules; vol. 20; 8; (2015); p. 15206 – 15223;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 2034-23-3, name is 5-Chloro-1H-benzo[d]imidazol-2(3H)-one, 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 2034-23-3, category: imidazoles-derivatives

Step 1. A mixture of 5-chloro-lH-benzo[d]imidazol-2(3H)-one (200 mg, 1.19 mmol), cesium carbonate (850 mg, 2.61 mmol) and tert-butyl 2-bromoacetate (0.37 mL, 2.5 mmol) in acetone (10 mL) was sealed and heated in an oil bath at 65 C for 6 h. The reaction mixture was filtered and concentrated in vacuo, taken up into DCM (20 mL), washed with 5% citric acid and brine, dried over MgSCn, filtered and concentrated in vacuo. The residual solid was recrystallized from 2: 1 hexanes-EtOAc (10 mL) to afford di-tert-butyl 2,2′-(5-chloro2-oxo-lH-benzo[d]imidazole-l,3(2H)-diyl)diacetate (160 mg) as a white solid. LC-MS retention time = 1.38 min; m/z = 285.1 [M-2(t-Bu)+H]+. (Column: Waters Aquity BEH C18 2.1 X 50 mm 1.7^m-particles; Solvent A = 100% Water/ 0.05% TFA; Solvent B = 100% Acetonitrile/0.05% TFA; Flow Rate = 0.8 mL/min. Start % B = 2; Final % B = 98; Gradient Time = 1.5 minutes; Wavelength = 220 nm).

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, 5-Chloro-1H-benzo[d]imidazol-2(3H)-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; VIIV HEALTHCARE (No.5) LIMITED; BENDER, John A.; LOPEZ, Omar D.; NGUYEN, Van N.; YANG, Zhong; WANG, Alan Xiangdong; WANG, Gan; MEANWELL, Nicholas A.; BENO, Brett R.; FRIDELL, Robert A.; BELEMA, Makonen; THANGATHIRUPATHY, Srinivasan; (350 pag.)WO2016/172425; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem