Month: August 2021

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. 10111-08-7, name is Imidazole-2-carboxaldehyde, A new synthetic method of this compound is introduced below., Application In Synthesis of Imidazole-2-carboxaldehyde

To a solution of 4-fluoronitrobenzene (7.87 g) and 2-imidazole-carboxaldehyde (5.90 g) in DMF (60 mL) was added K2CO3 (9.26 g). The mixture was heated at 80 C. under N2 for 16 h. The mixture was poured into water, and the precipitate was filtered to give 6.70 g of yellow solid. The filtrate was then extracted with EtOAc, and the organic layer was washed brine, dried over MgSO4, and concentrated to a yellow solid (5.40 g). Both batch were identified as the 4-[(2′-carboxaldehyde)imidazol-1′-yl]nitrobenzene. ESI mass spectrum z (rel. intensity) 218 (M+H, 100).

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; DuPont Pharmaceuticals Company; US6339099; (2002); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 20075-26-7,Some common heterocyclic compound, 20075-26-7, name is 1-(Methoxymethyl)-1H-imidazole, molecular formula is C5H8N2O, 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. Preparation of alpha-(2,4-dichlorophenyl)-1-(methoxymethyl)-alpha-phenylimidazole-2-methanol This compound was prepared by the procedure described in Example XXVII B, using the following materials: 9.8 g (0.088 mol) of 1-(methoxymethyl)imidazole, 10.4 g (0.09 mol) of N,N,N’,N’-tetramethylethylenediamine, 100 ml. of anhydrous tetrahydrofuran, 62 ml. (0.10 mol) of 15% butyl lithium in n-hexane, 22.6 g (0.09 mol) of 2,4-dichlorobenzophenone in 100 ml. of anhydrous tetrahydrofuran. The reaction mixture was decomposed with 75 ml. of water. The solid matter formed was filtered off and the aqueous phase of the filtrate was discarded. The organic phase was concentrated. The residue appeared to be identical to the solid matter filtered off. The combined solid substances were crystallized from isopropyl alcohol. alpha-(2,4-Dichlorophenyl)-1-(methoxymethyl)-alpha-phenylimidazole-2-methanol was obtained. Melting point 161-161.5 C.

The synthetic route of 20075-26-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Gist-Brocades N.V.; US4152441; (1979); A;,
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 641571-13-3 as follows. Computed Properties of C12H9F3N2O2

3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzoic acid (10 mg, 0.030 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (22 mg, 0.058 mmol), and TEA (7.9 mg, 0.078 mmol) were dissolved in DMF (0.2 ml), the solution was stirred at 45 C. for 30 minutes, and then the compound F (10 mg, 0.030 mmol) was added, followed by stirring the solution at 45 C. for 12 hours. After the reaction was completed, ethyl acetate was added, and the reaction mixture was washed with a saturated aqueous NaCl solution. The organic layer was dried with sodium sulfate anhydrous and filtered, and then the solvent was removed under reduced pressure. The residue was crystallized to obtain a target compound 3-(4-methyl-1H-imidazol-1-yl)-N-(4-(2-oxo-2,3-dihydro-1H-thieno[3,4-b][1,4]diazepine-4-yl)phenyl)-5-(trifluoromethyl)benzamide (10.3 mg, 67%). 1H NMR (400 MHz, DMSO-d6) delta 10.77 (1H, s), 10.53 (1H, s), 8.49 (1H, s), 8.43 (1H, s), 8.27 (1H, s), 8.19 (1H, s), 8.09 (2H, d, J=8.8 Hz), 7.95 (2H, d, J=8.8 Hz), 7.75 (1H, s), 7.52 (1H, d, J=4.0 Hz), 7.02 (1H, d, J=3.6 Hz), 3.61 (2H, s), 2.19 (3H, s) (Exact mass 509.11, m/z 510.1193)

According to the analysis of related databases, 641571-13-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Industry-University Cooperation Foundation Hanyang University ERICA Campus; HAH, Jung-Mi; LEE, Jung Hun; KIM, Minjung; (30 pag.)US2018/37589; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 1402838-08-7, name is 2-(1-Trityl-4-imidazolyl)benzaldehyde, 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 1402838-08-7, category: imidazoles-derivatives

1-(2-Hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)ethyl-1-one (100 mg, 0.46 mmol),2-(1-Triphenylmethyl-1H-imidazol-4-yl)benzaldehyde (190 mg, 0.46 mmol) was dissolved in tetrahydrofuran (4.0 mL).The sodium ethoxide solution (31 mg, 21%/wt%) was added dropwise and stirred at room temperature overnight.After TLC monitoring, the reaction was completed, the solvent was evaporated under reduced pressure, and saturated ammonium chloride solution (10 mL) was added.Extracted with dichloromethane (20 mL), and the organic phase was evaporated to dryness.The residue was used directly in the next step.The residue obtained above was dissolved in a mixed solution of methanol (4 mL) and acetic acid (1 mL).After reacting at 90 C for 3 h, TLC detected the reaction completely.The solvent was evaporated under reduced pressure and the residue was purified by flash column chromatography.Obtained the target Compound114mg,The yield was 72%.

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, 2-(1-Trityl-4-imidazolyl)benzaldehyde, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Suzhou Guokuang Pharmaceutical Technology Co., Ltd.; Hangzhou Anuo Bio-pharmaceutical Technology Co., Ltd.; Mei Desheng; Lu Yang; Yang Donghui; Li Pan; (50 pag.)CN108424415; (2018); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 17325-26-7, 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 17325-26-7 as follows.

To a mixture of methyl 1H-imidazole-4-carboxylate (2.0 g, 15.9 mmol) in DMF (30 mL), were added DIPEA (4.1 g, 31.72 mmol), then SEM-Cl (4.0 g, 23.4 mmol) dropwise. The reaction mixture was stirred at RT for 16 h, then quenched with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography over silica gel (EtOAc in PE 30~50%, v/v) to give methyl 1-((2- (trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxylate as a colorless oil (2.13 g, 52%). LC-MS (ESI): m/z (M+1)+ = 257.21.

According to the analysis of related databases, 17325-26-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; REMEDY PLAN, INC.; CRIMMINS, Gregory, Thomas; DE JESUS DIAZ, Dennise, Alexandra; BHURRUTH-ALCOR, Yushma; (483 pag.)WO2019/213570; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. 19225-92-4, name is 2-(Chloromethyl)-1-methyl-1H-imidazole, A new synthetic method of this compound is introduced below., category: imidazoles-derivatives

Intermediate 158 Methyl 2-((S)-6-((R)-4-(2,6-dimethyl-4-((1-methyl-1H-imidazol-2-yl)methoxy)phenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate [0988] Methyl 2-((S)-6-((R)-7-fluoro-4-(4-hydroxy-2,6-dimethylphenyl)-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate (Intermediate 28-29) (46.3 mg) and 2-(chloromethyl)-1-methyl-1H-imidazole (39.2 mg) were suspended in dimethylformamide (1.8 mL) and potassium carbonate (62 mg) was added. The reaction mixture was shaken for 24 h at 60 C. Another portion of 2-(chloromethyl)-1-methyl-1H-imidazole (39.2 mg) and potassium carbonate (62 mg) was added and the mixture was shaken again for 24 h at 60 C. and than directly chromatographed by HPLC on reversed phase. The product fractions are collected and lyophilized to give the title compound. Yield: 31.5 mg; LC (method 23): tR=1.54 min; Mass spectrum (ESI+): m/z=557 [M+H]+.

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; Boehringer Ingelheim International GmbH; ECKHARDT, Matthias; FRATTINI, Sara; HAMPRECHT, Dieter; HIMMELSBACH, Frank; LANGKOPF, Elke; LINGARD, Iain; PETERS, Stefan; WAGNER, Holger; US2013/252937; (2013); 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. 3034-38-6, name is 5-Nitro-1H-imidazole, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 5-Nitro-1H-imidazole

General Procedure:To a solution of 3-chloro-1-phenylpropan-1-one (2, 2.0 mmol) in toluene (25-30 mL) was added azoles (3.0 mmol) and triethylamine (4.0 mmol) at room temperature. The reaction mixture was heated at reflux under stirring for 3-4h in an oil bath. Solvent was distilled off under reduced pressure and the residue was taken into ethyl acetate (20 mL). Organic layer was washed with water (10 mL x 3) and dried over sodium sulfate. Sodium sulfate was filtered off and washed with ethyl acetate (5 mL x 2). The combined filtrate was concentrated under reduced pressure to yield crude product which was purified by recrystallization with ethyl acetate/hexane to give 3-(substituted 1H- azol-1-yl)-1-phenylpropan-1-one (3-9).

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 3034-38-6.

Reference:
Article; Kumar, Lalit; Sarswat, Amit; Lal, Nand; Jain, Ashish; Kumar, Sumit; Kiran Kumar; Maikhuri, Jagdamba P.; Pandey, Atindra K.; Shukla, Praveen K.; Gupta, Gopal; Sharma, Vishnu L.; Bioorganic and Medicinal Chemistry Letters; vol. 21; 1; (2011); p. 176 – 181;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 20485-43-2, 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 20485-43-2 as follows.

Example 16 rac-(3aR,14bR)-10-Cyclohexyl-N7-(dimethylsulfamoyl)-13-methoxy-N3a,N3a- dimethyl-2-((l-methyl-lH-imidazol-2-yl)carbonyl)-l,2,3,14b-tetrahydroindolo[2,l- a]pyrrolo[3,4-d][2]benzazepine-3a, 7(4H)-dicarboxamide. HATU (37.5 mg, 0.099 mmol) was added to a solution of rac-(3aR,14bR)-10-cyclohexyl-N7- (dimethylsulfamoyl)-13-methoxy-N3a,N3a-dimethyl-l,2,3,14b-tetrahydroindolo[2,l- alpha]pyrrolo[3,4-d][2]benzazepine-3a,7(4H)-dicarboxamide (30 mg, 0.049 mmol) and 1- methyl-lH-imidazole-2-carboxyIic acid (12.5 mg, 0.099 mmol) in DMF (1 mL) and TEA (0.03 mL, 0.2 mmol). The reaction mixture was stirred at rt for 16 h, diluted with MeOH, and purified by preparative HPLC (H2O/MeOH with 0.1% TFA buffer) to yield rac-(3aR,14bR)-10-cyclohexyl-N7-(dimethylsulfamoyl)-13-methoxy-N3a,N3a- dimethyl-2-(( 1 -methyl-1H-imidazol-2-yl)carbonyl)- 1 ,2,3 , 14b-tetrahydroindolo[2, 1 – alpha]pyrrolo[3,4-d][23benzazepine-3a,7(4H)-dicarboxamide (20.3 mg, 0.028 mmol, 57% yield) as a bright yellow solid. Complex mixture of rotamers was observed, partial 1H NMR (aromatic region) reported for 2 major rotamers (~3:2 ratio). 1H NMR (500 MHz, DMSO-d6) delta 6.78 (s, 0.6H), 6.91 (s, 0.4H), 7.00 (s, 0.4H), 7.05 (s, 0.4H), 7.08 – 7.22 (m, 2.2H), 7.32 (d, J= 8.2 Hz, 0.6H), 7.37 (d, J= 8.2 Hz, 0.4H), 7.54 (dd, J= 8.6, 1.2 Hz, 0.4H), 7.61 (dd, J= 8.6, 1.2 Hz, 0.6H), 7.81 (d, J= 8.6 Hz, 0.6H), 7.84 (d, J= 8.6 Hz, 0.4H), 8.09 (br s, 0.4H), 8.31 (br s, 0.6H), 11.31 (s, 0.4H), 11.69 (s, 0.6H). LCMS: m/e 716 (M+H)+, ret time 3.67 min, 4 minute gradient.

According to the analysis of related databases, 20485-43-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; WO2009/120733; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 3314-30-5, 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. 3314-30-5 name is 1H-Benzo[d]imidazole-2-carbaldehyde, 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 methyl diethylphosphonoacetate(3.17g, 15.0 mmol) in dry THF (40 mL) was added sodium carbonate (3.79 g, 27.4 mmol), the mixturewas stirred for 30 min at room temperature prior to the addition of compound 2 (2.0 g, 13.7 mmol).The mixture was stirred and refluxed for 24 h under an argon atmosphere and monitored by TLC.After complete conversion of starting material, the reaction mixture was filtered, the filtrate wasconcentrated and re-dissolved by ethyl acetate, and then washed with saturated NaCl solution anddried over anhydrous sodium sulfate, concentrated in vacuo and purified by flash silica gel column(PE/EA = 4/1, v/v) to obtain 3 as white solid in 87.5% yield. LC-MS m/z: 203.1 [M + H]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1H-Benzo[d]imidazole-2-carbaldehyde, and friends who are interested can also refer to it.

Reference:
Article; Wang, Shuxiang; Guan, Lihong; Zang, Jie; Xing, Kun; Zhang, Jian; Liu, Dan; Zhao, Linxiang; Molecules; vol. 24; 7; (2019);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

These common heterocyclic compound, 33543-78-1, name is Ethyl 1H-imidazole-2-carboxylate, 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. Safety of Ethyl 1H-imidazole-2-carboxylate

(Reference Example 8) Synthesis of ethyl 1-(difluoromethyl)-1H-imidazole-2-carboxylate: Potassium carbonate (1.28 g, 9.28 mmol) and sodium chlorodifluoroacetate (1.31 g, 8.56 mmol) were added to a solution of ethyl 1H-imidazole-2-carboxylate (1.00 g, 7.14 mmol) in acetonitrile (35 mL) at room temperature and the resultant mixture was stirred at 60°C for 24 hours. Further, potassium carbonate (0.640 g, 4.63 mmol) and sodium chlorodifluoroacetate (0.660 g, 4.33 mmol) were added at room temperature and the reaction liquid was stirred at 80°C for 8 hours. The reaction liquid was cooled to room temperature and distilled water was added to the reaction liquid and the reaction liquid was extracted with ethyl acetate. The organic layer was washed with a 10percent aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, hexane/ethyl acetate) to obtain ethyl 1-(difluoromethyl)-1H-imidazole-2-carboxylate (0.838 g, 4.41 mmol, 62percent) as a colorless oil. 1H-NMR (400 MHz, CDCl3) delta: 1.46 (3H, t, J=7.2 Hz), 4.47 (2H, q, J=7.2 Hz), 7.28 (1H, s), 7.53 (1H, d, J=1.6 Hz), 8.16 (1H, t, J=60.8 Hz).

The synthetic route of Ethyl 1H-imidazole-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Toray Industries, Inc.; ARAI Tadamasa; MORITA Yasuhiro; UDAGAWA Shuji; ISEKI Katsuhiko; IZUMIMOTO Naoki; (95 pag.)EP3263565; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem