Category: imidazoles-derivatives

Synthetic Route of 39861-21-7, 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. 39861-21-7, name is 4-(5-Chloro-1H-benzo[d]imidazol-2-yl)aniline, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: Further, compounds 4 (0.35-0.50 mmol, 1.0 eq) were heated withchloroacetyl chloride (3.0 eq) in anhydrous toluene (10 mL) to 90 C for2 h. This reaction mixture was concentrated under reduced pressureand the residue was triturated with diethyl ether (10 mL). The productwas filtered and subsequently washed with multiple portions of diethylether (3×5 mL) and dried to recover colored solids. The solids werevigorously stirred in a saturated solution of NaHCO3 (10 mL) for30 min, acidified to neutral pH by aqueous 1M HCl solution and thenextracted with multiple portions of ethyl acetate (5×10 mL) until theaqueous layer turns colorless. The combined organic extracts werewashed with brine (10 mL), dried over sodium sulfate (10 g), were filteredand concentrated to yield pure amides 5 as colored solids in70-90% yield.

The chemical industry reduces the impact on the environment during synthesis 4-(5-Chloro-1H-benzo[d]imidazol-2-yl)aniline. I believe this compound will play a more active role in future production and life.

Reference:
Article; Ankenbruck, Nicholas; Kumbhare, Rohan; Naro, Yuta; Thomas, Meryl; Gardner, Laura; Emanuelson, Cole; Deiters, Alexander; Bioorganic and Medicinal Chemistry; vol. 27; 16; (2019); p. 3735 – 3743;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 870837-18-6, 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. 870837-18-6 name is 3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde, 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.

Synthesis of (Z)-(6S*,9aR*)-6-(4-fluorophenyl)-3-[1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]hexahydropyrido[2,1-c][1,4]oxazin-4-one Triethylamine (0.03 mL) was added to a solution of [(6R*,9aS*)-6-(4-fluorophenyl)-4-oxooctahydropyrido[2,1-c][1,4]oxazin-3-yl]triphenylphosphonium bromide (57 mg) and 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde (21 mg) in ethanol (5 mL), and the reaction solution was stirred at room temperature for two hours. The reaction solution was concentrated under reduced pressure. Then, the residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane:ethyl acetate=1:1->ethyl acetate) to obtain 27 mg of the title compound. The property values of the compound are as follows. 1H-NMR (CDCl3) delta (ppm): 1.40-1.58(m,2H), 1.65-1.76(m,2H), 2.18-2.25(m,2H), 2.31(s,3H), 3.85(s,3H), 4.07(q,J=10.8 Hz,1H), 4.07-4.15(m,1H), 4.34(dd,J=10.8,2.4 Hz,1H), 5.38(t,J=4.0 Hz,1H), 6.82(s,1H), 6.92(brs,1H), 7.02(t, J=8.4 Hz,2H), 7.20(d,J=8.0 Hz,1H), 7.22(dd,J=8.0,3.6 Hz,2H), 7.37(dd,J=8.0,1.2 Hz,1H), 7.39(d,J=1.2 Hz,1H), 7.74(d,J=1.2 Hz,1H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde, and friends who are interested can also refer to it.

Reference:
Patent; Eisai R&D Management Co., Ltd.; US2007/117798; (2007); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 2302-25-2,Some common heterocyclic compound, 2302-25-2, name is 4-Bromo-1H-imidazole, molecular formula is C3H3BrN2, 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.

General procedure: A mixture of 4-methyl-3-(4-(pyridin-2-ylmethoxy)benzamido)phenyl boronic acid (50 mg, 0.14 mmol), Cs2CO3 (135 mg, 0.41 mmol), Pd(PPh3)4(23.93 mg, 0.02 mmol) and 4-bromo-1H-imidazole (26 mg, 0.18 mmol) was purged with nitrogen before adding degassed dioxane (690 muL) and water (230 muL) and heating in a microwave for 40 min at 150 C. After cooling, the aqueous layer was removed with a pipette, and the organic layer was diluted with DMSO (1 mL) and filtered through a 0.2 mum filter. The filtrate was concentrated to a volume of 1 mL and purified by Gilson HPLC (20-75% MeCN/10 mM NH4OAc in water). The fractions were concentrated and lyophilized to yield the product (19 mg, 0.049 mmol, 35%). 1H NMR (DMSO-d6) delta ppm 12.11 (s, 1H), 9.76 (s, 1H), 8.59 (d, 1H), 7.97 (d, 2H), 7.85 (td, 1H), 7.70 (s, 1H), 7.67 (s, 1H), 7.56 (m, 2H), 7.36 (dd, 1H), 7.21 (d, 1H), 7.15 (d, 2H), 5.27 (s, 2H), 2.18 (s, 3H). LCMS (M+H) = 385.

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

Reference:
Review; Yang, Bin; Hird, Alexander W.; Russell, Daniel John; Fauber, Benjamin P.; Dakin, Les A.; Zheng, Xiaolan; Su, Qibin; Godin, Robert; Brassil, Patrick; Devereaux, Erik; Janetka, James W.; Bioorganic and Medicinal Chemistry Letters; vol. 22; 14; (2012); p. 4907 – 4911;,
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. 5465-29-2, name is 2-Propylbenzimidazole, A new synthetic method of this compound is introduced below., Application In Synthesis of 2-Propylbenzimidazole

Step A: 2-Propyl-1-(4-(2–t-butoxycarbonylbenzoyl)phenyl)methylbenzimidazole To a suspension of NaH (0.013 mg) in dry DMF (3 ml), 2-propyl benzimidazole (0.052 g, 0.325 mmol) was added, and the mixture was stirred at room temperature for 30 minutes to give a clear solution. To the solution was added t-butyl-2-[4–(bromomethyl)benzoyl]benzoate (0.125 g, 0.33 mmol) [prepared according to the procedure described in European Patent Application 0,253,310]. The mixture, after stirring at room temperature for 3 hours, was poured into ice-water (50 ml) and extracted with ethyl acetate (3 x 20 ml). The combined organic phase was washed with brine, then dried (MgSO4), and evaporated. The crude product was then purified by flash chromatography on silica-gel using ethyl acetate-hexane (1:6). Yield 0.12 g (81%, as amorphous solid). NMR(CDCl3): delta 1.0 (t, J=7Hz, 3H), 1.26 (s, 9H), 1.88 (m, 2H), 2.86 (t, J=7Hz, 2H), 5.4 (s, 2H), 7.05-7.8 (m, 12H); FAB-MS: m/e 455 (M+H).

The synthetic route of 5465-29-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Merck & Co., Inc.; EP400835; (1990); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

10111-08-7, name is Imidazole-2-carboxaldehyde, 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. Safety of Imidazole-2-carboxaldehyde

To a suspension of NaH (60% in mineral oil, 1.45 g, 36.2 mmol) in DMF (30 mL) was added 2-imidazolecarboxaldehyde (3.00 g, 30.3 mmol) portionwise, and the mixture was stirred at RT for 1 h, then treated with 2-(trimethylsilyl)ethoxymethyl chloride (5.91 mL, 33.3 mmol). The mixture was stirred at RT overnight, then treated with sat. aq. NH4C1 and extracted with EtOAc (3 X 45 mL). The combined organic layers were washed with sat. aq. NaC1 (6 X 30 mL), dried over Na2 SO4, and concentrated under reduced pressure. The residue was purified by Si02 gel chromatography (0/o to 25% EtOAc in CH2C12) to give the title compound as a colorless oil (2.18 g, 32%). ?HNMR (400 MHz. CDC13) oe 9.86 (s, 1H), 7.39 (s, 1H), 7.36 (s, 1H), 5.80 (s, 2H), 3.66-3.47 (m, 2H), 0.98-0.90 (m, 2H), 0.01 (s, 9H).

The synthetic route of 10111-08-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOARD OF REGENTS, UNIVERSITY OF TEXAS SYSTEM; SOTH, Michael, J.; JONES, Philip; RAY, James; LIU, Gang; LE, Kang; CROSS, Jason; (141 pag.)WO2018/44808; (2018); A1;,
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

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

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

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

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