Category: imidazoles-derivatives

Application of 89830-98-8, These common heterocyclic compound, 89830-98-8, name is 5-Cyclopropyl-1H-imidazole, 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.

NaH (60 mass%) in minera oi (148 mg, 3.6989 mmo) is added to a soution of 4-cycopropy-1H-imidazoe (200 mg, 1.8495 mmo) in DMF (2 mL) at 0 C under anitrogen atmosphere. The mixture is stirred at 0 C for 15 minutes. 1 ,2-Dibromoethane(0.504 mL 5.5484 mmo) is added at 0 C and the mixture is stirred at room temperaturefor 4 hours under a nitrogen atmosphere. The reaction is quenched by addition of water.The mixture is extracted with EtOAc (3x). The organic phase is washed with saturatedNaC (3x), dried over Na2SO4, fitered, and concentrated to dryness. The residue ispurified by siica ge flash chromatography with 3% MeOH in DCM to give the titecompound as a mixture of 1-(2-bromoethy)-4-cycopropy-imidazoe and 1-(2- bromoethy)-5-cycopropy-imidazoe regioisomers (120 mg, 28.7%) as a cooress oi. ES/IVIS (m/z): 215 (M+1).

The synthetic route of 89830-98-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; LILLY CHINA RESEARCH AND DEVELOPMENT CO., LTD.; LIU, Lian Zhu; WANG, Xiaoqing; WILEY, Michael Robert; (34 pag.)WO2019/50794; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 5955-72-6, A common heterocyclic compound, 5955-72-6, name is 2-Chloro-6-nitro-1H-benzo[d]imidazole, molecular formula is C7H4ClN3O2, 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.

Step 3. NaH (60%) in mineral oil was added portion-wise to a stirred suspension of 2-chloro-5- nitro-lH-benzo[d] imidazole (A/1482/81/1) in dry DMF at 0 C under a nitrogen atmosphere The ice-bath was removed, and the reaction mixture was stirred at RT. After 0.5 h the mixture was cooled to 0 C, and 2-trimethylsilylethyoxymethyl chloride (0.38 mL) was added drop-wise. The ice-bath was removed, and the resulting reaction mixture was stirred at RT. After lh, UPLC showed complete conversion. A saturated ammonium chloride solution and EA were added, the organic phase was separated, washed with water, dried over sodium sulfate and the solvent removed under vacuum. The crude material was purified by FC on silica (Snap 100, eluting with Cy EA from 100/0 to 80/20) to give the desired product A/1482/82/1 as yellow oil. Step 4. To a solution of methyl glycolate in dry THF (8 ml) cooled at 0 C was added NaH (60%) in mineral oil. The reaction was stirred at room temperature for 2h. The suspension was cooled at 0 C and a solution of A/1482/82/1 was added dropwise. The reaction mixture was stirred at room temperature for 16h. UPLC showed ~70% reaction completion, and another 1.1 eq of NaH was added. After stirring for 16h, UPLC showed formation of side products. The reaction was stopped, and S. NH4C1 and EtOAC were added. The organic phase was separated, dried and evaporated to give a crude product, which was then purified by silica column (CyHex to CyHex: EtOAc= 85:15). The product named A/1482/83/1 was recovered with a 50% of purity grade (by NMR), with the UPLC retention time of the impurity that same as that of the desired product. Step 5. To a stirred solution oh the A/1482/83/1 cooled to 0 C in THF, a solution of LiOH in water was added dropwise. The mixture was then stirred at room temperature for 2h. UPLC showed complete conversion. The solvent was evaporated under vacuum. The residue was portioned between water and EtOAc, the organic phase was separated and discarded. The water phase was evaporated to give the desired product as the corresponding lithium salt A/1482/84/1. Step 6. To a stirred solution of A/1482/84/1, 4-aminobenzonitrile and TEA in THF 3: 1, HATU was added at room temperature. After stirring for 5h, UPLC showed complete conversion. The solvent was evaporated and the residue partitioned between saturated aqueous NaHC03 and DCM. The organic phase was separated, dried and the solvent evaporated to give an impure product, which was further purified by Si02 column (DCM to DCM:MeOH). The desired product named A/1540/23/1 was recovered as a white solid.

The synthetic route of 5955-72-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; THE GENERAL HOSPITAL CORPORATION; ZAHLER, Robert; WESTER, Ronald Thure; BRICKNER, Steven Joseph; WO2014/176258; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 1003-21-0, A common heterocyclic compound, 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, molecular formula is C4H5BrN2, 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.

Example 2Synthesis of [2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-[l-(3- methylimidazol-4-yl)pyrazol-4-yl]methanone.Place [2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-(lH- pyrazol-4-yl)methanone (0.142 g, 0.40 mmoles), 5-bromo-l-methyl-imidazole (89 mg, 0.55 mmoles), cesium carbonate (257 mg, 0.79 mmoles), (1R,2R)- diaminomethylcyclohexane (16 mg, 0.12 mmoles), and copper(I) iodide (7.50 mg, 0.039 mmoles) in a microwave reaction vessel. Add toluene (2 mL) and dimethylformamide (2 mL). The vessel is sealed and purged three times and heated at 110C for 48 hrs. The reaction is allowed to cool to room temperature and is quenched with water (2 mL). Extract three times with ethyl acetate. Dry over sodium sulfate, filter and concentrate under reduced pressure. The residue is purified by reverse phase chromatography to give the title compound (0.078 g, 0.42%). LCMS (m/z): 441.2 (M+l).

The synthetic route of 1003-21-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; BLEISCH, Thomas John; DOTI, Robert Anthony; PFEIFER, Lance Allen; NORMAN, Bryan Hurst; WO2014/168824; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 14486-52-3, The chemical industry reduces the impact on the environment during synthesis 14486-52-3, name is 1-Methyl-2-(methylthio)imidazole, I believe this compound will play a more active role in future production and life.

General procedure: 1-Methylimidazole (0.49 g, 6.05 mmol) was added to a stirred solution of Key Intermediate-1 (2.3 g, 4.03 mmol) in acetonitrile (25 mL) at RT. The reaction mixture was heated to 90 C for 16 h and concentrated under reduced pressure. The crude material was triturated with diethyl ether (2 x 10 mL) to afford a brown solid (2.4g) which was used in the next steps without further purification. M/z 616.38 (M)+ TFA: H2O (9:1, 20 mL) was added to the brown solid (2.4 g) at RT. The reaction mixture was stirred for 3 h and concentrated under reduced pressure. The resulting crude product was triturated with diethyl ether (2 x 5 mL) and dried under high vacuum. The crude product was purified by preparative HPLC affording the title product as off-white solid (515 mg, 30% over 2 steps).

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-2-(methylthio)imidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Antabio SAS; DAVIES, David; LEIRIS, Simon; (56 pag.)EP3572411; (2019); 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. 616-47-7, name is 1-Methyl-1H-imidazole, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C4H6N2

General procedure: N-methyl imidazole (17.53 ml, 0.22 mol) and 1,4-butane sultone (20.5 ml, 0.20mol) were dissolved in toluene (60 ml) and stirred for 8h at 60ºC under nitrogen atmosphere. The white zwitter ion solid so formed was filtered and washed repeatedly with diethyl ether (3 × 40 ml) to remove non-ionic residues.The resulting solid (MIM-BS) was dried in vacuum for 8h. The MIM-BS (10.0 gm,0.0463 mol) was dissolved in water (2 ml) with constant stirring.Methanesulfonic acid (3 ml, 0.0463 mol) was taken in water (1 ml) and added to the reaction contents dropwise. The mixture was stirred for 6h at 85ºC. After completion of the reaction, water was removed and contents were dried for 24h under reduced pressure. The resulting colorless viscous liquid was stored in dry box for further use.

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 616-47-7.

Reference:
Article; Garg, Bhaskar; Ling, Yong-Chien; Tetrahedron Letters; vol. 53; 42; (2012); p. 5674 – 5677;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 152628-02-9,Some common heterocyclic compound, 152628-02-9, name is 1,7′-Dimethyl-2′-propyl-1H,1’H-2,5′-bibenzo[d]imidazole, molecular formula is C19H20N4, 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 4. 4′-[[4-Methyl-6-(1-methyl-2-benzimidazolyl)-2-propyl-1-benzimidazolyl]methyl]-2-biphenylcarboxylic acid (telmisartan) (4′-Methyl-2′-propyl-1H-benzimidazol-6′-yl)-1-methyl benzimidazole (3.0 g, 9.8 mmol), 4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)benzyl methanesulfonate (3.12 g, 10 mmol), tetrahydrofuran (15 ml) and potassium carbonate (1.38 g, 10 mmol) are loaded into a round-bottom flask equipped with magnetic stirrer, condenser and under nitrogen atmosphere. The mixture is stirred at room temperature for 8 hours, then 10% hydrochloric acid is added to pH=2. THF is evaporated off, which causes precipitation of boronic acid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1,7′-Dimethyl-2′-propyl-1H,1’H-2,5′-bibenzo[d]imidazole, its application will become more common.

Reference:
Patent; Dipharma S.p.A.; EP1719766; (2006); A2;,
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. 150058-27-8, name is Methyl 2-ethoxy-1H-benzo[d]imidazole-7-carboxylate, A new synthetic method of this compound is introduced below., Application In Synthesis of Methyl 2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

To a solution of methyl 2-ethoxy-lH-benzo[d]imidazole-7-carboxylate (55.5 mg, 0.252 mmol) in DMF (2 mL) was added sodium hydride (60percent) (16.78 mg, 0.420 mmol) at RT. The reaction mixture was stirred for 10 min at RT before methyl 4″-(bromomethyl)- [l,l’:3′, l”-terphenyl]-4′-carboxylate (Intermediate 400b, 80 mg, 0.210 mmol) was added in its own solution of DMF (1 niL). After 50 min of stirring at RT the reaction mixture was diluted with EtOAc and washed with 10percent LiCl (aq). The organic phase was dried over MgS04, filtered over celite, and concentrated. The residue was dissolved DMF and purified by ISCO (0-100percent EtOAc/Hexanes) to afford the title compound (Intermediate 314a, 48 mg, 0.069 mmol, 33.0 percent yield). LC-MS Retention time (Method A2) = 1.20 min. Found m/z: 520.1 (M+H)+. H NMR (400MHz, CDC13) delta 7.89 (d, 7=8.1 Hz, 1H), 7.66 – 7.57 (m, 4H), 7.55 – 7.49 (m, 2H), 7.49 – 7.31 (m, 4H), 7.22 (d, 7=8.4 Hz, 2H), 7.01 (d, 7=8.1 Hz, 2H), 5.66 (s, 2H), 4.68 (q, 7=7.1 Hz, 2H), 3.78 (s, 3H), 3.57 (s, 3H), 1.54 – 1.48 (m, 3H).

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; UNIVERSITE DE MONTREAL; BRISTOL-MYERS SQUIBB COMPANY; PRIESTLEY, Eldon, Scott; REZNIK, Samuel, Kaye; RUEDIGER, Edward, H.; GILLARD, James, R.; HALPERN, Oz, Scott; JIANG, Wen; RICHTER, Jeremy; RUEL, Rejean; TRIPATHY, Sasmita; YANG, Wu; ZHANG, Xiaojun; (642 pag.)WO2018/5591; (2018); 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 7189-69-7 as follows. Recommanded Product: 7189-69-7

To a solution of phenethylamine (34, 0.15mmol) in THF (5mL), triethylamine (0.15mmol) was added. To this mixture, 1,1′-sulfonyldiimidazole (0.15mmol) was added and the reaction mixture was stirred at 60C for 2h. After the completion of the reaction monitored by TLC, water was added and the reaction mixture was extracted using ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The obtained intermediate 36 was used for next step without further purification. In the next step, 3-phenylpropylamine (0.15mmol) was dissolved in THF and triethylamine (0.15mmol) was added. To this mixture, 36 was added. The reaction was stirred at 60C for 3h. The reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was quenched with water and the whole mixture was extracted using ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude mixture was purified by column chromatography to afford the pure product 3. Yield 72%, Pale yellow solid. Rf 0.30 (2: 1 Ethylacetate: Hexane), mp. 135-137C; IR (neat): 3362, 2950, 2822, 1560, 1523, 1345, 1170, 945cm-1. 1H NMR (CDCl3) delta 1.79-1.87 (m, 2H), 2.64 (t, J=8.00Hz, 2H), 2.85 (t, J=7.20Hz, 2H), 2.92-2.97 (m, 2H), 3.28-3.33 (m, 2H), 4.07-4.13 (m, 2H), 7.15-7.33 (m, 10H); 13C NMR (CDCl3) delta 31.13, 32.94, 35.81, 42.68, 44.31, 126.35, 127.04, 128.50, 128.71, 128.97, 128.98, 138.10, 141.04. HRMS Calcd for C17H22N2O2S m/z [M+H] 319.1481, found 319.1507.

According to the analysis of related databases, 7189-69-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Manickam, Manoj; Jalani, Hitesh B.; Pillaiyar, Thanigaimalai; Sharma, Niti; Boggu, Pulla Reddy; Venkateswararao, Eeda; Lee, You-Jung; Jeon, Eun-Seok; Jung, Sang-Hun; European Journal of Medicinal Chemistry; vol. 134; (2017); p. 379 – 391;,
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. 15965-54-5, name is 2-Chloro-5-methoxy-1H-benzo[d]imidazole, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2-Chloro-5-methoxy-1H-benzo[d]imidazole

Preparation 21 tert-Butyl 2-chloro-5-methoxy-1H-1,3-benzimidazole-1-carboxylate STR66 Di-tert-butyldicarbonate (523 mg) was added to a solution of 2-chloro-5-methoxy-1H-1,3-benzimidazole (364 mg) and dimethylaminopyridine (24 mg) in acetonitrile (4 ml). The reaction mixture was stirred at room temperature for 30 minutes, after which time the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluding with a solvent gradient of 90:10 changing to 85:15, by volume, hexane:ethyl acetate to afford tert-butyl 2-chloro-5-methoxy-1H-1,3-benzimidazole-1-carboxylate (470 mg) as an off-white solid, as a 1:1 mixture of regioisomers. 1 H-NMR (CDCl3)delta: 7.80 (0.5H, d), 7.55 (0.5H, d), 7.50 (0.5H, s), 7.15 (0.5H, s), 7.00 (1H, t), 3.85 (3H, s), 1.70 (9H, s).

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 15965-54-5.

Reference:
Patent; Pfizer Inc; US6166011; (2000); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 33543-78-1, name is Ethyl 1H-imidazole-2-carboxylate, 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 33543-78-1, Safety of Ethyl 1H-imidazole-2-carboxylate

Ethyl 1H-imidazole-2-carboxylate at 0 C(40.01 g, 285.5 mmol) in a dry THF (600 mL) suspension Sodium hydride (13.82 g, 345.5 mmol, mass fraction 60%) was added.The reaction mixture was stirred at room temperature for 1 hour and then cooled to 0 C.O-(2,4-dinitrophenyl)hydroxylamine (80.00 g, 401.8 mmol) was added portionwise.The reaction system was stirred at room temperature overnight and then diluted in water (600 mL).The resulting mixture was extracted with EA (600 mL×10).The separated organic phase was dried over anhydrous sodium sulfate, filtered and evaporated.The residue obtained is purified by silica gel column chromatography (EA/PE (v/v) = 1/2 to 1/1 to 2/1).The title compound is a brown solid(37.6 g, yield 85%).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Jiatuo Sciences Corporation; Xi Ning; Li Xiaobo; Li Minxiong; Zhang Tao; Hu Haiyang; Wu Yanjun; (102 pag.)CN108570048; (2018); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem