Imidazoles-derivatives

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

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

A common heterocyclic compound, 3543-73-5, name is Ethyl 4-(5-amino-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, molecular formula is C14H19N3O2, 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. 3543-73-5.

To a solution of 81.3 g (650.6 mmol) 2-bromoethanol, 1 g potassium iodide and 100 g water was added 17.0 g (65 mmol) compound (6). The reaction mixture was heated to 65-70 C. and held at this temperature for 8 h to 12 h. The pH value of the solution was held between 4.2-5.5 during this period by dropwise addition of a solution of 20.0 g (151.4 mmol) diammonium hydrogen phosphate in 35 g water. The control of pH over the duration of the reaction was effected through use of a pH electrode. The conversion was followed by HPLC. The reaction was continued until the fraction of compound (7A) was ?1.5%. Thereby ca. 8% of compound (7B) had formed and the proportion of compound (7) was ca. 87%. The reaction mixture was subsequently concentrated to dryness at ca. 55-60 C. under vacuum. To the residue was added 150 g water and, preferably with an alkali metal carbonate, the pH value adjusted to ca. 8.5. The desired product (7) was extracted with 200 g methylene chloride or 225 g chloroform, and the organic phase subsequently washed with 60-80 g water. The organic phase was then concentrated to dryness and the remaining oil or already crystalline residue dissolved in 200 g ethyl acetate or alternatively in 60 g acetonitrile. Compound (7) crystallised at ca. 5 C. and was filtered under suction, washed with 20 g cold ethyl acetate or alternatively with 15 g cold acetonitrile and dried at 60-70 C. The yield of compound (7) was 18.3 g (52.4 mmol) with a content of ?98.2% (80.5% of theory). The crude contained ?0.6% compound ( 7A) and compound (7B) respectively as well as <0.15% of compound (7C). The crude product obtained was recrystallized from ethyl acetate, or alternatively from acetonitrile, toluene, propan-2-ol, tetrahydrofuran, acetone, isopopyl acetate or water, prior to further conversion to compound ( 8). Thereby the yield of compound (7) was 17.2 g (94.0% recrystallization yield) with a content of >99.2%, wherein compound (7A) was removed below a content of 0.2% and compound (7B) below 0.3%. Through the course of the reaction, the content of compound (7C) was kept below 0.15%, as this compound can only poorly be removed by recrystallization from the above described solvents. The overall yield of this step was 76.5% of theory and was thus ca. 12.5% higher than that described in the procedure using ethylene oxide as according to DD34727 and ca. 31% higher in comparison to the favoured procedure of WO2011079193 involving addition of Huenig’s base.

The synthetic route of Ethyl 4-(5-amino-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Heyl Chemisch-pharmazeutische Fabrik GmbH & Co. KG; Frey, Michael; Walther, Dirk-Detlef; US2014/31560; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

4887-80-3, name is 5-Methoxy-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. 4887-80-3

General procedure: An excess of 5-substituted benzoimidazoles 4a-d (1.5 equiv.) were dissolved in 8 mL of anhydrous acetonitrile and 1.7 equiv. NaH 95% were added portionwise under stirring in a Schlenk tube at room temperature, applying mechanical vacuum until complete evolution of hydrogen gas. After 15 minutes, 1 g (7.14 mmol) of the 4-hydroxy-2-cyclopentenone acetate (¡À)-1 was dissolved in the minimum amount of anhydrous acetonitrile and added to the solution under stirring. The reactions are left under stirring at room temperature overnight. The reactions were quenched with ice mixed with NaCl/NH4Cl 1:3 and the water phase extracted with DCM. The organic phases were dried over Na2SO4 and, upon evaporation of the solvent, the residues were submitted to chromatographic separation to isolate the purified products 5/6a-d

Statistics shows that 4887-80-3 is playing an increasingly important role. we look forward to future research findings about 5-Methoxy-1H-benzo[d]imidazole.

Reference:
Article; Hameed, Karzan Khaleel; Dezaye, Ahmed Anwar; Hussain, Faiq Hamasaid; Basile, Teresa; Memeo, Misal Giuseppe; Quadrelli, Paolo; Arkivoc; vol. 2018; 7; (2018); p. 201 – 213;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

10111-08-7, 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 10111-08-7 as follows.

General procedure: A typical procedure involves, in a round-bottom flask equipped with a refluxcondenser, in which a mixture of 4-hydroxycoumarin (2 mmol), arylaldehyde(1 mmol), PIL catalyst (10 mol%) and 5 mL of ethanol was stirred at 80 C.The reaction was monitored by TLC. After completion of the reaction, a solidproduct is obtained which is filtered and recrystallized with ethanol(Scheme 2).

According to the analysis of related databases, Imidazole-2-carboxaldehyde, the application of this compound in the production field has become more and more popular.

Reference:
Article; Patil, Sandip K.; Awale, Deepak V.; Vadiyar, Madagonda M.; Patil, Suryakant A.; Bhise, Sagar C.; Kolekar, Sanjay S.; Research on Chemical Intermediates; vol. 43; 10; (2017); p. 5365 – 5376;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding some certain compound to certain chemical reactions, such as: 24134-09-6, name is 5-Bromo-1,2-dimethyl-1H-imidazole, 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 24134-09-6. 24134-09-6

Intermediate 11: bis(1,2-dimethyl-1H-imidazol-5-yl)methanone A solution of -RuLi (2.66 M in hexane, 19.5 mL, 51.9 mmol) in THF (100 mL) was stirred under argon at-70 C while a solution of 5-bromo-l ,2-dimethyI-lH-imidazole (9.13 g, 52.2 mmol) in TFIF [60 mL; containing 3A molecular sieves (18 g)] was added dropwise over 8 minutes via cannula. After stirring for another 4 minutes at ~-70 C, neat ethyl metboxy(methyl)carbamate (2.96 mL, 22.7 mmol) was added dropwise over 3 minutes. This mixture was stirred at-70 C for an additional 5 minutes, and the cold bath was then removed and the slurry was allowed to warm to room temperature with stirring for 1.5 hours. The reaction was then quenched with 5 aqueous NH4C1 (15 mL), dried (Na2S04), filtered, and concentrated under high vacuum at 80 C, The resulting orange gummy residue was triturated with hot heptane (-40 mL) and the decanted supernatant was allowed to crystallize to provide impure title compound. This was recrystallized from toluene (-30 niL) to provide, after washing the off-white crystalline filter cake with toluene (2 x ~3 mL), the title compound as an off-white crystalline solid.

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 5-Bromo-1,2-dimethyl-1H-imidazole.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; LEONARD, Kristi A.; BARBAY, Kent; EDWARDS, James P.; KREUTTER, Kevin D.; KUMMER, David A.; MAHAROOF, Umar; NISHIMURA, Rachel; URBANSKI, Maud; VENKATESAN, Hariharan; WANG, Aihua; WOLIN, Ronald L.; WOODS, Craig R.; FOURIE, Anne; XUE, Xiaohua; CUMMINGS, Maxwell D.; JONES, William Moore; GOLDBERG, Steven; WO2015/57205; (2015); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

934-32-7, Name is 1H-Benzo[d]imidazol-2-amine, 934-32-7, 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.

General procedure: A mixture of aldehyde (1 mmol), 2-aminobenzimidazole (1 mmol), malononitrile (1.1 mmol), RHA-[pmim]HSO4 (10 mg, 0.8 mol %) was heated in an oil bath at 100 C under solvent-free conditions for the appropriate time. After completion of the reaction (monitored by TLC), EtOH was added and the catalyst was separated by filtration. Then water was added, and the precipitated product was separated by filtration in high purity. The spectral data of the new compound are as follows:

Statistics shows that 1H-Benzo[d]imidazol-2-amine is playing an increasingly important role. we look forward to future research findings about 934-32-7.

Reference:
Article; Shirini, Farhad; Seddighi, Mohadeseh; Goli-Jolodar, Omid; Journal of the Iranian Chemical Society; vol. 13; 11; (2016); p. 2013 – 2018;,
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 2034-22-2 as follows. 2034-22-2

2,4,5-tribromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole To a solution of 2,4,5-tribromoimidazole (3.05 g, 10 mmol) in anhydrous DMF (50 mL) was added powdered K2CO3 (19 g, 137 mmol), and the resulting suspension was stirred vigorously and treated dropwise with SEMCl (2.3 g, 13.8 mmol). The suspension was then stirred vigorously overnight. The solid was filtered off and washed with fresh DMF (20 mL). The combined filtrates were then evaporated under reduced pressure. Methylene chloride (30 mL) was then added and the solution washed with 0.1 N Na2CO3 (3*50 mL), dried (Na2SO4), filtered and evaporated to give a residue, which was passed through a silica gel pad (CH2Cl2) and evaporated to give 3.6 g (83%) of the title compound as a colorless oil. 1H NMR (500 MHz, CDCl3) delta 0.01 (s, 9H), 0.93 (t, 2H, J=8.0 Hz), 3.60 (t, 2H, J=8.0 Hz), 5.32 (s, 3H).

According to the analysis of related databases, 2034-22-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Hudyma, Thomas W.; Zheng, Xiaofan; He, Feng; Ding, Min; Bergstrom, Carl P.; Hewawasam, Piyasena; Martin, Scott W.; Gentles, Robert G.; US2006/46983; (2006); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – 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. 60-56-0 name is 1-Methyl-1H-imidazole-2(3H)-thione, 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. 60-56-0

3-methoxy salicylaldehyde 5 (1 mmol), malononitrile 6 (2.2 mmol), 2-mercaptoimidazole 7 (1.2 mmol), compound4 (20 mol%) and ethanol (5 mL) were sequentially added to a 50 mL round bottom flask, and fully reacted to completion at 80 C (TLC tracking supervision) Measurement). After cooling to room temperature, suction filtration, the product was washed with a small amount of water, dissolved in N,N-dimethylformamide, filtered, and evaporated. The distilled water was precipitated as a solid, suction filtered, and recrystallized (DMSO) to give compound 8j in a yield of 80%. The structural formula of compound 8j is:The formula is: C18H15N6OSChinese name: 2,4-diamino-9-methyl-5-(1-methyl-1H-imidazol-2-ylthio)-5H-chromene[2,3-b]pyridine-3-carbonitrileThe English name is: 2,4-diamino-9-methyl-5-(1-methyl-1H-imidazol-2-ylthio)-5H-Chromeno[2,3-b]pyridine-3-carbonitrile

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Methyl-1H-imidazole-2(3H)-thione, and friends who are interested can also refer to it.

Reference:
Patent; Jiangsu Normal University; Wu Hui; Yuan Rui; Ren Xuanxuan; Fang Yue; Chen Wen; Zhou Shengliang; Zhang Peng; Wan Yu; (15 pag.)CN108610348; (2018); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

2849-93-6, A common compound: 2849-93-6, name is 1H-Benzimidazole-2-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.

STEP 7: N-(CIS-3-(7,7-DIMETHYL-6-OXO-6,7-DIHYDRO-5H-PYRROLO[2,3-B]PYRAZIN-5-YL)CYCLOBUTYL)-1H-BENZO[D]IMIDAZOLE-2-CARBOXAMIDE To a round bottomed flask was added 5-(cis-3-aminocyclobutyl)-7,7-dimethyl-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one (0.1518 g, 0.497 mmol), 1H-benzimidazole-2-carboxylic acid (0.097 g, 0.597 mmol, ChemBridge Corporation), 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.246 g, 0.647 mmol, GenScript) and triethylamine (0.277 ml, 1.989 mmol, Sigma-Aldrich Chemical Company, Inc.) in DCM (1.658 ml) to stir at room temperature for 5 h. Solvent was evaporated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (50 g), eluting with a gradient of 10% to 100% EtOAc in hexane. LCMS showed product was not isolated at ?95%. The crude product was taken up in DCM and loaded onto an AccuBond SCX cartridge. The cartridge was rinsed with DCM followed by MeOH to remove impurities. The column was then rinsed with 2.0 ammonia in MeOH. The fractions were evaporated in vacuo. The residue was taken up in MeOH at which time a precipitate was noted to form. The round bottomed flask was placed in the freezer overnight. The solid was filtered from the filtrate and washed with cold MeOH to give the title compound (17.1 mg, 0.045 mmol, 9.13% yield). LCMS showed product peak at 1.757 min (m+1=377.0). 1H NMR (400 MHz, DMSO-d) delta ppm 1.35 (s, 6H) 2.71-2.85 (m, 2H) 2.95-3.11 (m, 2H) 4.35 (sxt, J=7.94 Hz, 1H) 4.59 (quin, J=8.46 Hz, 1H) 7.31 (br. s., 2H) 7.55 (d, J=6.26 Hz, 1H) 7.77 (d, J=6.65 Hz, 1H) 8.20 (d, J=3.13 Hz, 1H) 8.27 (d, J=3.13 Hz, 1H) 9.28 (d, J=7.83 Hz, 1H) 13.27 (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, 1H-Benzimidazole-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; AMGEN INC.; Allen, Jennifer R.; Amegadzie, Albert; Andrews, Kristin L.; Brown, James; Chen, Jian J.; Chen, Ning; Harrington, Essa Hu; Liu, Qingyian; Nguyen, Thomas T.; Pickrell, Alexander J.; Qian, Wenyuan; Rumfelt, Shannon; Rzasa, Robert M.; Yuan, Chester Chenguang; Zhong, Wenge; US2013/225552; (2013); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem