Category: imidazoles-derivatives

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.

Ethylmagnesium bromide (3 M in Et2O, 1.04 mL, 3.11 mmol) was added dropwise to a solution of 5-bromo-1-methyl-1H-imidazole (500 mg, 3.11 mmol) in DCM (6 mL) under a nitrogen atmosphere. The mixture was stirred at room temperature 15 min, then was cooled in an ice bath prior to addition of N-methoxy-N-methylpyridazine-4-carboxamide (419 mg, 2.51 mmol, Intermediate 29, step a). The resulting suspension was stirred at room temperature for 2 hours. The reaction was quenched by addition of saturated aqueous NH4Cl, diluted with water, and extracted three times with EtOAc. The aqueous phase was saturated with NaCl and back-extracted with DCM (three times). The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, gradient 30-100% CH3CN-DCM, followed by isocratic 5% MeOH-acetone), affording title compound contaminated with 1-methyl-1H-imidazole, the mixture of which was used in the next reaction without further purification.

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; 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; Mirzadegan, Taraneh; Ganamet, Kelly; US2014/107097; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

60-56-0, name is 1-Methyl-1H-imidazole-2(3H)-thione, 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. HPLC of Formula: C4H6N2S

Triethylamine (0.0749 g, 0.75 mmol) was added to a solution of2-mercapto-1-methylimidazole (0.0856 g, 0.75 mmol) in tetrahydrofuran(15 mL) and the mixture was stirred for 30 min at roomtemperature. Then, 1-(bromomethyl)pyrene (0.1476 g, 0.5 mmol)was slowly added and the reaction mixture was heated underreflux for 24 h. After cooling to room temperature, the mixture wasfiltered and the solvent was evaporated, the crude residue waspurified by column chromatography (1:1 ethyl acetate/petroleumether) to obtain a brown solid of compound 2 (0.1301 g, 79.3%yield). Characterization of compound 2: 1H NMR600 MHzd6-DMSO3.62 (s, 3H), 3.87 (d, 2H), 7.12 (s, 1H), 7.45 (s, 1H), 7.63(dd, 2H), 8.15 (m, 1H), 8.28 (d, 1H), 8.32 (m, 2H), 8.36 (m, 2H), 8.38(d, 1H), 8.50 (d, lH). Mass spectra (Fig. S2): calculated for C21H16N2S[M+H]+, 329.1; found, 328.81.

The synthetic route of 60-56-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Wang, Jing; Jiang, Huihui; Liu, Hai-Bo; Liang, Lebao; Tao, Junrong; Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy; vol. 228; (2020);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 288-32-4,Some common heterocyclic compound, 288-32-4, name is 1H-Imidazole, molecular formula is C3H4N2, 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 imidazole (1 mmol), phenylboronic acid (2 mmol), K2CO3 (2 mmol), Cu(CH3COO)2H2O (1 mol %, 1.99 mg) and L1 (1 mol %, 5.7 mg) in ethanol (5 mL) was stirred at room temperature in a 50 mL oven dried round bottomed flask. After the completion of the reaction (as monitored by TLC), conventional workup of the reaction mixture was done with ethyl acetate (3 × 15 mL) and water (10 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered and the solvent was evaporated in a rotary evaporator under reduced pressure to get the crude product. The crude product was purified by column chromatography on silica gel (DCM: Methanol = 9:1) to afford the pure product.

The synthetic route of 288-32-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Baruah, Jayantajit; Gogoi, Kongkona; Dewan, Anindita; Borah, Geetika; Bora, Utpal; Bulletin of the Korean Chemical Society; vol. 38; 10; (2017); p. 1203 – 1208;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 89088-69-7,Some common heterocyclic compound, 89088-69-7, name is 1-Methyl-1H-imidazol-4-amine hydrochloride, molecular formula is C4H8ClN3, 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.

To a solution of 2,4-dichlorofuro[3,2-d]pyrimidine (la) (0.71 g, 3.74 mmol; CAS 956034- 07-4) in 2-Propanol (20 mL) was added DIPEA (1.63 mL, 9.36 mmol), 1-methyl-1H-imidazol-4-amine hydrochloride (0.5 g, 3.74 mmol) and heated at reflux for 24 h. The reaction mixture was concentrated in vacuum to dryness and the residue obtained was triturated with water. The solid obtained was collected by filtration and dried in vacuum to afford 2-chloro-N-(l-methyl-lH-imidazol-4-yl)furo[3,2-d]pyrimidin-4-amine (lb) (550 mg,59 % yield) as brown solid; NMR (300 MHz, DMSO-^) delta 10.89 (s, 1H, D20exchangeable), 8.35 (d, J = 2.1 Hz, 1H), 7.52 (d, J = 1.6 Hz, 1H), 7.39 (d, J = 1.3 Hz, 1H), 7.03 (d, J = 2.1 Hz, 1H), 3.71 (s, 3H); MS (ES+): 250.3 (M+l), 272.3, 274.3 (M+Na), (ES-): 248.2 (M-l).

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

Reference:
Patent; BIOCRYST PHARMACEUTICALS, INC.; KOTIAN, Pravin, L.; BABU, Yarlagadda, S.; KUMAR, V., Satish; ZHANG, Weihe; LU, Peng-Cheng; RAMAN, Krishnan; (747 pag.)WO2018/232094; (2018); A1;,
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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. 6160-65-2, name is 1,1′-Thiocarbonyldiimidazole, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 1,1′-Thiocarbonyldiimidazole

Description 19: S-Bromo-lH-benzoimidazole^-sulfonic acid; [00281] Thiocarbonyl diimidazole (0.95 g, 5.35 mmol) was added in one portion to a solution of 4-bromobenzene-l,2-diamine (1.00 g, 2.67 mmol) in TetaF (50 mL). The mixture was stirred for 6 h then the solvents were removed in vacuo. The residue was suspended in DCM and the product was collected by filtration as a white solid. This was dissolved in KOeta solution (IM, 10.7 mL, 10.7 mmol) and eta2O2 (30 %, 2.13 mL, 21.40 mmol) was added dropwise. The mixture was stirred for 14 h then concentrated HCl was added to pH 1. The mixture was cooled to 0 0C for 30 min then the white solid product was collected by filtration. This was dried at 40 0C under high vacuum (1.15 g, 77 %). MS (MH+, m/z) 275 (50 %), 277 (50 %).

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 6160-65-2.

Reference:
Patent; GALAPAGOS N.V.; WO2008/55959; (2008); 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. 4856-97-7, name is (1H-Benzoimidazol-2-yl)methanol, This compound has unique chemical properties. The synthetic route is as follows., Safety of (1H-Benzoimidazol-2-yl)methanol

To a three-necked flask was added 1.24 g (6 mmol) of dicyclohexylcarbodiimide, 0.12 g (lmmol) of 4-dimethylaminopyridine, followed by addition of 25 mL of tetrahydrofuran, After stirring and dissolving, Adding 1. 03 g (5 mmol) of 5-nitroindol-3-carboxylic acid, After stirring for half an hour at room temperature, 0.75 g (5 mmol) of 2-light methylbenzimidazole was added and stirred at room temperature for 8 h to stop the reaction. The reaction was filtered, the filtrate was distilled, dried and dissolved in dichloro Methane, standing at room temperature until a large amount of precipitate precipitated, filtered, washed with water, dried in vacuo to give 1.28g (1H-benzimidazol-2-yl) methyl-5-nitro-1H-indole-3-carboxylate in a yield of 76. 19percent.

According to the analysis of related databases, 4856-97-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Qingdao University of Science & Technology; Kang, Congmin; Wang, XinYing; Liu, yizhou; (5 pag.)CN105315262; (2016); A;,
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. 3273-68-5, name is 4-(2-Oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)butanoic acid, A new synthetic method of this compound is introduced below., 3273-68-5

Part A. Preparation of chloro 2,3-dihydro-2-oxo-lH-benzimidazol-l- butanoate.4-(2-oxo-2,3- chloro 2,3-dihydro-2-oxo- dihydrobenzimidazol-l-yl)butyric acid lH-benzimidazol-1-butanoate4-(2-Oxo-2,3-dihydrobenzimidazol-l-yl)butyric acid (50 g; 0.227 mol), N ,N- dimethylformamide (1.84 g; 0.025 mol; 0.11 eq), and dichloromethane (480 g; 5,652 mol; 24.89 eq) were charged to a stirred-tank reactor. Oxalyl chloride (31.12 g; 0.245 mol; 1.08 eq) was then dosed at 10-200C over a 1-hour period while stirring. The resulting mixture was then stirred at 10-200C for an additional hour. All the above steps were conducted under a N2 atmosphere.; Part A. Preparation of chloro 2,3-dihydro-2-oxo-lH-benzimidazol-l- butanoate.4-(2-oxo-2,3- chloro 2,3-dihydro-2-oxo- dihydrobenzimidazol-l-yl)butyric acid lH-benzimidazol-1-butanoateDichloromethane (3772 L) and then 4-(2-oxo-2,3-dihydrobenzimidazol-l-yl)butyric acid (525 kg; 2.4 kmol) were charged to a stirred-tank reactor, followed by N5N- dimethylformamide (21 L). The resulting mixture was cooled to 1O0C. Afterward, oxalyl chloride (326.8 kg)) was dosed at 10-150C over 2-3 hours while stirring. The resulting mixture was then stirred at 15-2O0C for an additional 1-3 hours. All the above steps were conducted under a N2 atmosphere. Conversion was checked by in-process control (“IPC”).

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; INTERVET INTERNATIONAL B.V.; WO2008/119754; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. 405173-97-9, name is 2-(2-Chloroethyl)-1H-benzo[d]imidazole belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 405173-97-9

General procedure: 2-(2-Aminoethyl)-N-[(3-fluoropyridin-2-yl)methyl]-1 ,3-thiazole-4-carboxamide dihydrochloride (103) (2.0 g, 3.96 mmol) was added to a solution of 2-(2-chloroethyl)-1 H-1 ,3-benzodiazole hydrochbride (1.12 g, 5.15 mmol) and DIPEA (10.6 ml, 59.45 mmol) in DMF (60 ml). The reaction mixture was allowed to stir at 3GC for 6 d (reaction was monitored by LCMS). The mixture was concentrated in vacuo and the residue was neutralised using sat. NaHC03 (aq). The aqueous layer was extracted using 4: 1 CHCb / 1 PA (4 x 100 ml) and the combined organic layers were dried (MgS04), filtered and evaporated in vacuo. The crude residue was purified by flash column chromatography (kp-NH, eluting with a gradient of 60-100% EtOAc / heptane followed by 0-20% MeOH / EtOAc) follow by neutral reverse-phase column chromatography (gradient elution 0-60% MeCN / water) to give the title compound (0.173 g, 10%) as a yellow oil. 1 H-NMR (Methanol-d4, 500 MHz): d[ppm]= 8.31 (d, J = 4.6 Hz, 1 H), 8.02 (s, 1 H), 7.57 (t, J = 9.1 Hz, 1 H), 7.45 – 7.40 (m, 2H), 7.36 (dd, J = 8.6, 4.3 Hz, 1 H), 7.17 (dd, J = 6.0, 3.2 Hz, 2H), 4.68 (s, 2H), 3.26 (d, J = 6.8 Hz, 2H), 3.15 – 3.07 (m, 6H) HPLCMS (Method D): [m/z]: 425.1 [M+H]+In a similar fashion to general procedure 7, -(pyridin-2-ylmethyl)-4H,5H,6H,7H-thieno[2,3-c]pyridine-3- carboxamide (450) (65 mg, 0.24 mmol), K2C03 (49 mg, 0.36 mmol) and 2-(2-chloroethyl)-1 H- benzimidazole (47 mg, 0.26 mmol) in acetone (3 ml) at room temperature for 24 h, followed by the addition of DMF (5 ml), Nal (39 mg, 0.26 mmol), DIPEA (0.16 ml, 0.95 mmol) and 2-(2-chloroethyl)-1 H- benzimidazole (94 mg, 0.52 mmol) at room temperature for 72 h, gave the title compound (9 mg, 9%) as an orange solid after purification by basic prep-HPLC. 1 H-NMR (DMSO-d6, 500 MHz): d[ppm]= 12.17 (s, 1 H), 8.75 (t, J = 6.0 Hz, 1 H), 8.50 (d, J = 4.2 Hz, 1 H), 7.94 (s, 1 H), 7.75 (td, J = 7.7, 1.8 Hz, 1 H), 7.46 (s, 2H), 7.31 (d, J = 7.8 Hz, 1 H), 7.28- 7.23 (m, 1 H), 7.10 (dd, J = 6.0, 3.1 Hz, 2H), 4.48 (d, J = 6.0 Hz, 2H), 3.71 (s, 2H), 3.05 (t, J = 7.2 Hz, 2H), 2.96 (t, J = 7.2 Hz, 2H), 2.82 (d, J = 5.3 Hz, 2H), 2.75 (t, J = 5.7 Hz, 2H) HPLCMS (Method B): [m/z]: 418.2 [M+H]+

The synthetic route of 405173-97-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VIFOR (INTERNATIONAL) AG; DUeRRENBERGER, Franz; BUHR, Wilm; BURCKHARDT, Susanna; BURGERT, Michael; KALOGERAKIS, Aris; REIM, Stefan; MANOLOVA, Vania; BOYCE, Susan; YARNOLD, Christopher John; PENA, Paula; SHEPHERD, Jon; LECCI, Cristina; JARJES-PIKE, Richard; SCOTT, John; (416 pag.)WO2017/68089; (2017); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1450-93-7, name is 1H-imidazol-2-amine sulfate(2:1), 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: 1450-93-7

2-Aminoimidazole sulfate (11.6 g) is dissolved in 7.4 mL of concentrated HCl, 8 mL of water, and 40 mL of acetic acid. The resulting solution is cooled to 0 C. To the solution is added a solution of 6.08 g of NaNO2 in 16 mL of water dropwise where the internal temperature is maintained under 5 C. The resulting yellow-brown solution is stirred for 30 minutes at 0 C. In a separate flask equipped with a mechanical stirrer a mixture of 1,4-diethyl-1,2,3,4-tetrahydroquinoxaline, 13.1 g of sodium acetate and 40 mL of acetic acid is cooled to 0 C. To this slurry is added the diazonium solution slowly and the internal temperature of the reaction is maintained below 5 C. After the addition is complete, the resulting violet suspension is stirred for 1 hour at 0 C. The dark reaction mixture is poured into a large beaker containing 400 g ice. Aqueous NaOH (20%) is added to the suspension slowly until pH 6.5 is reached. The mixture is extracted with dichloromethane 6 times to yield crude (E)-6-((1H-imidazol-2-yl)diazenyl)-1,4-diethyl-1,2,3,4-tetrahydroquinoxaline (19.5 g, impure). This material is used in the next step without further purification.

The synthetic route of 1450-93-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; The Procter & Gamble Company; MURPHY, Bryan Patrick; ZHANG, Guiru; ZHAO, Jielu; (32 pag.)US2018/72970; (2018); A1;,
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Imidazole | C3H4N2 – PubChem

Related Products of 14741-71-0, The chemical industry reduces the impact on the environment during synthesis 14741-71-0, name is Ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate, I believe this compound will play a more active role in future production and life.

2.00 g (9.79 mmol) of ethyl (2-benzimidazolyl)acetate was added to a mixture of 1.83ml (19.6mmol) of phosphoryl chloride and 2.28 ml (29.4 mmol) of N,N-dimethylformamide at 0C, and the resulting mixture was heated at 95C for 50 minutes. After cooling, 50 ml of ice-water was added thereto, and potassium carbonate was added to this mixture until it became alkaline, and then this was extracted with chloroform (100 ml x 3). The chloroform layers were combined and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was washed with ethyl acetate and taken out through filtration to obtain a dark brown crystal. Butyric anhydride (10 ml) suspension of the dark brown crystal synthesized above was heated at 170C for 70 minutes. After cooling, the solvent was evaporated under reducedpressure, and the residue was washed with diisopropyl ether and taken out through fil tration to obtain 713 mg (26%) of the entitled compound (I-80) as an orange crystal. MS(EI)m/z:285(M+).1H-NMR(40OMHz, DMSO-d6)delta: 1.16(3H, t, J=7.33Hz), 1.34(3H, t, J=7.08Hz), 2.45-2.60(2H, m), 4.34(2H, q, J=7.08Hz), 7.31-7.39(1H, m), 7.48-7.53(1H, m), 7.68(1H, d, J=7.81Hz), 7.85(1H, s), 8.67(1H, d, J=7.81Hz). IR(ATR): 3203, 1685, 1637, 1606, 1552, 1462, 1369, 1323, 1240, 1182, 1134, 1107, 1090 cm-1.

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, Ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; DAIICHI PHARMACEUTICAL CO., LTD.; EP1479681; (2004); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem