Category: 3543-74-6

Application of 3543-74-6, These common heterocyclic compound, 3543-74-6, name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, 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.

Preparation of Bendamustine Hydrochloride (Crude) (0099) Step 1: 4-{5-[Bis-(2-hydroxy-ethyl)-amino]-1-methyl-1H-benzoimidazol-2-yl}-butyric acid ethyl ester (27.0 kg) was dissolved in 270 kg chloroform. After cooling to 0 to 5 C., 19.2 kg thionyl chloride was added over about 1 hour. The mixture was warmed to 25 C.±5 C. and stirred for 20 to 24 hours. 75.6 kg hydrochloric acid (32% aqueous solution) was then added. After phase separation, the organic (lower) phase was removed. The product remained in the aqueous phase. (0100) Step 2: A suspension of activated charcoal in hydrochloric acid was added to the aqueous phase obtained in step 1. The mixture was heated over 1 hour to 85 to 90 C. and stirred for 4 to 5 hours at reflux. The suspension was then filtered and rinsed with aqueous hydrochloric acid. The solvent was distilled off under reduced pressure at a temperature not exceeding 65 C. 108 kg to 324 kg (108 kg preferred) of warm (35 to 45 C.) deionized water was added to induce crystallization. (0101) After crystallization, the mixture was cooled to 20 C±5 C. and stirred for an additional 1 to 2 hours or overnight. The product was collected by filtration on a filter dryer, washed with three portions each of 108 to 324 kg (108 kg preferred) deionized water and 108 to 216 kg (108 kg preferred) of cold acetone. The crude product was treated four times each with 54 to 108 kg (54 kg preferred) acetone at reflux for at least 1 hour, in the filter dryer. The suspension was filtered and the product dried at a temperature not higher than 40 C. under reduced pressure, to give 21.4 kg±2.1 kg bendamustine hydrochloride crude (70%±10%, calculated as dried substance). (0102) Step 3 (optional): The product obtained from step 2 was dissolved in hydrochloric acid (32% aqueous solution) and heated to reflux (85 to 90 C.) for at least 4 hours. To improve color, activated charcoal can be added to the hydrochloric acid and the mixture heated to reflux (85 to 90 C.) for at least 4 hours. With activated charcoal, the suspension was filtered and rinsed with aqueous hydrochloric acid. Solvent was distilled off under reduced pressure at a temperature not exceeding 65 C. The mixture was then diluted with deionized water. If no crystallization occurred within 15 min, the mixture was seeded. After crystallization, the suspension was stirred at 40 C.±5 C. for one hour, then cooled to 20 C.±5 C. After stirring an additional 1 to 2 hours at 20 C.±5 C., the product was collected by filtration, washed three times with cold deionized water, and at least three times with cold acetone. The crude product was treated four times with acetone at reflux for at least 1 hour. The suspension was filtered and the product dried at a temperature not higher than 40 C., under reduced pressure. Yield was of crude bendamustine hydrochloride was 80%±10%. Preparation of Purified Bendamustine Hydrochloride (0103) Bendamustine HCl crude (15.0 kg) was suspended with 0.45 kg activated charcoal in ethanol/water (vol/vol=97/3) at room temperature. The mixture was quickly warmed to 75 to 80 C. and stirred for not more than 10 min under reflux conditions. The mixture was filtered to remove the activated charcoal. After filtration, 33.0 kg of filtered acetone was added quickly at 40-50 C. to induce crystallization. (0104) After crystallization, the mixture was stirred for 30 to 60 min at 40-50 C., then cooled to 0 to 5 C., and stirred for at least an additional 30 min or overnight. The product was collected by filtration and washed with three 45 kg of cold acetone. After that, the crude product was treated 4 times each with 30 kg acetone at reflux for at least 1 hour. The suspension was filtered and the product dried at a temperature not higher than 40 C. under reduced pressure providing 11.3±1.5 kg bendamustine hydrochloride (75%±10%).

The synthetic route of 3543-74-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Cephalon, Inc.; Cooper, Martin Ian; Courvoisier, Laurent D.; Eddleston, Mark; McKean, Robert E.; (31 pag.)US2016/159748; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 3543-74-6, name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, 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 3543-74-6, Product Details of 3543-74-6

Example-2 Preparation of Ethyl 4-{5-[bis(2-chloroethyl)amino]-1-methyl-1H-benzimidazol-2-yl}butanoate (IV) 4-{5-[bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-2-yl}butanoate (III, 90.0 g, 1.15 mole) was added to dichloromethane (6.24 L) and agitated till clear solution is formed. A solution of thionyl chloride (292.3 g, 2.52 mol) in dichloromethane (1.56 L) was added slowly in 2 to 3 hours. After complete addition of thionyl chloride solution, reaction mixture was refluxed at 35-45 C. for 6 hours. The reaction mixture was cooled to 20-30 C. and 1.95 L dichloromethane was added. Potassium carbonate solution (351.0 g in 1.95 L water) was added to the reaction mixture slowly to control the evaluation of effervescence. The layers were separated. The organic (dichloromethane) layer was washed with brine solution. The organic layer was concentrated at 30-35 C. under vacuum till viscous mass is obtained. The viscous mass was dissolved in acetone (1.95 L) and DM water (1.365 L) was slowly. The resulting mixture was stirred at 20-30 C. for one hour followed by cooling to 0-5 C. The solid separated out was washed with chilled mixture of acetone (390 mL) and DM water (195.5 mL) twice. The material was sucked dried to dryness and used as such for next step.

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 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; FRESENIUS KABI ONCOLOGY LIMITED; MISHRA, Bhuwan Bhaskar; KACHHADIA, Nikunj Shambhubhai; TOMAR, Vinod Singh; LAHIRI, Saswata; US2014/121383; (2014); 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. 3543-74-6, name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, A new synthetic method of this compound is introduced below., COA of Formula: C18H27N3O4

Example 20: Preparation of crude Bendamustine hydrochloride (form B) [00103] A 5 L bottle was charged with 197 g of phosphorus oxychloride. The contents of the bottle were heated to 50 0C and 150 g of ethyl 4-{5-[bis(2- hydroxycthyl)amino]-l -methyl- lH-benzimidazol-2-yl}butanoatc(“BBOH”) dissolved in 600 ml of dichloromethane was added. Reaction mixture was stirred at 75-85 0C for 4-5 hours. The reaction mixture was then cooled to room temperature and diluted with 450 ml dichloromethane to form a solution. Then the solution was decomposed with 900 ml of 21 % hydrochloric acid and then this reaction mixture was heated at 92 – 96 C for 5-6 h. The resulting solution was then cooled, and its pH was adjusted with 50 % sodium hydroxide to a pH of 1.4 – 1.6 at 0 – 200C. The product crystallized and the mixture was stirred 30 – 60 minutes at 0-100C. The crude Bendamustine was separated by filtration and the filter cake was washed three times with 600 ml of cold dilute hydrochloric acid (1 :20), then three times with 600 ml of cold water, and then three times with 600 ml of ethyl acetate . The filter cake was then dried in wet (relative humidity over 30 %) nitrogen to give 144 g of crude bendamustine hydrochloride.

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; PLUS CHEMICALS SA; TEVA PHARMACEUTICALS USA, INC.; KUCHAR, Martin; KORYTAKOVA, Romana; POSPISILIK, Karel; GAVENDA, Ales; VRASPIR, Pavel; JEGOROV, Alexandr; WO2010/144675; (2010); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 3543-74-6, These common heterocyclic compound, 3543-74-6, name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, 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.

Preparation of Bendamustine Hydrochloride (Crude) (0099) Step 1: 4-{5-[Bis-(2-hydroxy-ethyl)-amino]-1-methyl-1H-benzoimidazol-2-yl}-butyric acid ethyl ester (27.0 kg) was dissolved in 270 kg chloroform. After cooling to 0 to 5 C., 19.2 kg thionyl chloride was added over about 1 hour. The mixture was warmed to 25 C.±5 C. and stirred for 20 to 24 hours. 75.6 kg hydrochloric acid (32% aqueous solution) was then added. After phase separation, the organic (lower) phase was removed. The product remained in the aqueous phase. (0100) Step 2: A suspension of activated charcoal in hydrochloric acid was added to the aqueous phase obtained in step 1. The mixture was heated over 1 hour to 85 to 90 C. and stirred for 4 to 5 hours at reflux. The suspension was then filtered and rinsed with aqueous hydrochloric acid. The solvent was distilled off under reduced pressure at a temperature not exceeding 65 C. 108 kg to 324 kg (108 kg preferred) of warm (35 to 45 C.) deionized water was added to induce crystallization. (0101) After crystallization, the mixture was cooled to 20 C±5 C. and stirred for an additional 1 to 2 hours or overnight. The product was collected by filtration on a filter dryer, washed with three portions each of 108 to 324 kg (108 kg preferred) deionized water and 108 to 216 kg (108 kg preferred) of cold acetone. The crude product was treated four times each with 54 to 108 kg (54 kg preferred) acetone at reflux for at least 1 hour, in the filter dryer. The suspension was filtered and the product dried at a temperature not higher than 40 C. under reduced pressure, to give 21.4 kg±2.1 kg bendamustine hydrochloride crude (70%±10%, calculated as dried substance). (0102) Step 3 (optional): The product obtained from step 2 was dissolved in hydrochloric acid (32% aqueous solution) and heated to reflux (85 to 90 C.) for at least 4 hours. To improve color, activated charcoal can be added to the hydrochloric acid and the mixture heated to reflux (85 to 90 C.) for at least 4 hours. With activated charcoal, the suspension was filtered and rinsed with aqueous hydrochloric acid. Solvent was distilled off under reduced pressure at a temperature not exceeding 65 C. The mixture was then diluted with deionized water. If no crystallization occurred within 15 min, the mixture was seeded. After crystallization, the suspension was stirred at 40 C.±5 C. for one hour, then cooled to 20 C.±5 C. After stirring an additional 1 to 2 hours at 20 C.±5 C., the product was collected by filtration, washed three times with cold deionized water, and at least three times with cold acetone. The crude product was treated four times with acetone at reflux for at least 1 hour. The suspension was filtered and the product dried at a temperature not higher than 40 C., under reduced pressure. Yield was of crude bendamustine hydrochloride was 80%±10%. Preparation of Purified Bendamustine Hydrochloride (0103) Bendamustine HCl crude (15.0 kg) was suspended with 0.45 kg activated charcoal in ethanol/water (vol/vol=97/3) at room temperature. The mixture was quickly warmed to 75 to 80 C. and stirred for not more than 10 min under reflux conditions. The mixture was filtered to remove the activated charcoal. After filtration, 33.0 kg of filtered acetone was added quickly at 40-50 C. to induce crystallization. (0104) After crystallization, the mixture was stirred for 30 to 60 min at 40-50 C., then cooled to 0 to 5 C., and stirred for at least an additional 30 min or overnight. The product was collected by filtration and washed with three 45 kg of cold acetone. After that, the crude product was treated 4 times each with 30 kg acetone at reflux for at least 1 hour. The suspension was filtered and the product dried at a temperature not higher than 40 C. under reduced pressure providing 11.3±1.5 kg bendamustine hydrochloride (75%±10%).

The synthetic route of 3543-74-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Cephalon, Inc.; Cooper, Martin Ian; Courvoisier, Laurent D.; Eddleston, Mark; McKean, Robert E.; (31 pag.)US2016/159748; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 3543-74-6, The transformation of simple hydrocarbons into more complex and valuable products via catalytic C¨CH bond functionalisation has revolutionised modern synthetic chemistry. 3543-74-6, Name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, SMILES is O=C(OCC)CCCC1=NC2=CC(N(CCO)CCO)=CC=C2N1C, belongs to imidazoles-derivatives compound. In a article, author is Kuzu, Burak, introduce new discover of the category.

Mono- or di-substituted imidazole derivatives for inhibition of acetylcholine and butyrylcholine esterases

Mono- or di-substituted imidazole derivatives were synthesized using a one-pot, two-step strategy. All imidazole derivatives were tested for AChE and BChE inhibition and showed nanomolar activity similar to that of the test compound donepezil and higher than that of tacrine. Structure activity relationship studies, docking studies to on X-ray crystal structure of AChE with PDB code 1B41, and adsorption, distribution, metabolism, and excretion (ADME) predictions were performed. The synthesized core skeleton was bound to important regions of the active site of AChE such as the peripheral anionic site (PAS), oxyanion hole (OH), and anionic subsite (AS). Selectivity of the reported test compounds was calculated and enzyme kinetic studies revealed that they behave as competitive inhibitors, while two of the test compounds showed noncompetitive inhibitory behavior. ADME predictions revealed that the synthesized molecules might pass through the blood brain barrier and intestinal epithelial barrier and circulate freely in the blood stream without binding to human serum albumin. While the toxicity of one compound on the WS1 (skin fibroblast) cell line was 1790 mu M, its toxicity on the SH-SY5Y (neuroblastoma) cell line was 950 mu M.

Application of 3543-74-6, The reactant in an enzyme-catalyzed reaction is called a substrate. Enzyme inhibitors cause a decrease in the reaction rate of an enzyme-catalyzed reaction.I hope my blog about 3543-74-6 is helpful to your research.

Chemistry, like all the natural sciences, COA of Formula: C18H27N3O4, begins with the direct observation of nature¡ª in this case, of matter.3543-74-6, Name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, SMILES is O=C(OCC)CCCC1=NC2=CC(N(CCO)CCO)=CC=C2N1C, belongs to imidazoles-derivatives compound. In a document, author is Nowak, Krystyna, introduce the new discover.

Synthesis of new imidazole derivatives

The derivatives of 1-propyl- and 1-butyl- of 2-methyl-5-nitroimidazole containing phenylpiperazine, m-chloro- and o-methoxyphenylpiperazine attached at the end of alkyl chain were synthesed. For the obtained new compounds, the biological activity was predicted using the computer program PASS.

Note that a catalyst decreases the activation energy for both the forward and the reverse reactions and hence accelerates both the forward and the reverse reactions. you can also check out more blogs about 3543-74-6. COA of Formula: C18H27N3O4.

In an article, author is Gracias, V, once mentioned the application of 3543-74-6, Formula: C18H27N3O4, Name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, molecular formula is C18H27N3O4, molecular weight is 349.4247, MDL number is MFCD09840918, category is imidazoles-derivatives. Now introduce a scientific discovery about this category.

Synthesis of fused triazolo-imidazole derivatives by sequential van Leusen/alkyne-azide cycloaddition reactions

A facile synthesis of fused triazolo imidazole derivatives by a van Leusen/alkyne-azide cycloaddition synthetic sequence is reported. The two-step reaction sequence generates compounds of significant molecular complexity from simple starting materials in an expedient fashion with good overall yields. (c) 2005 Elsevier Ltd. All rights reserved.

If you are interested in 3543-74-6, you can contact me at any time and look forward to more communication. Formula: C18H27N3O4.

Chemistry is an experimental science, Quality Control of Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, and the best way to enjoy it and learn about it is performing experiments.Introducing a new discovery about 3543-74-6, Name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, molecular formula is C18H27N3O4, belongs to imidazoles-derivatives compound. In a document, author is He, Xi-Xin.

Pelopuradazole, a new imidazole derivative alkaloid from the marine bacteria Pelomonas puraquae sp. nov.

One new imidazole derivative alkaloid pelopuradazole (1), together with three known alkaloids as in 3H-imidazole-4-carboxylic acid (2), 1H-pyrrole-2-carboxylic acid (3) and 2-methyl-3H-imidazole-4-carboxylic acid (4) and two known cyclo-dipeptides pelopurin A (5) and pelopurin B (6), has been isolated from the marine bacterium Pelomonas puraquae sp. nov. Pelopuradazole (1) was a new imidazole derivative alkaloid, while compounds 2, 3, 5 and 6 were firstly obtained as natural products. Compounds 1-6 were isolated from P. puraquae sp. nov. for the first time.

Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 3543-74-6, in my other articles. Quality Control of Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate.

Chemistry, like all the natural sciences, COA of Formula: C18H27N3O4, begins with the direct observation of nature¡ª in this case, of matter.3543-74-6, Name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, SMILES is O=C(OCC)CCCC1=NC2=CC(N(CCO)CCO)=CC=C2N1C, belongs to imidazoles-derivatives compound. In a document, author is Olgen, S, introduce the new discover.

Synthesis of 2 ‘-deoxy-2 ‘-fluoro-L-arabinofuranosyI imidazole derivatives

A now series of imidazole nucleosides was synthesized via direct condensation and construction of heterocyclic moiety from glycosyl amine templates. The characterization of the compounds was accomplished by elemental analysis, H-1-NMR, C-13-NMR, IR, UV-VIS spectral data and optical rotation.

Note that a catalyst decreases the activation energy for both the forward and the reverse reactions and hence accelerates both the forward and the reverse reactions. you can also check out more blogs about 3543-74-6. COA of Formula: C18H27N3O4.

Catalysts are substances that increase the reaction rate of a chemical reaction without being consumed in the process. 3543-74-6, Name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, SMILES is O=C(OCC)CCCC1=NC2=CC(N(CCO)CCO)=CC=C2N1C, belongs to imidazoles-derivatives compound. In a document, author is KNOLKER, HJ, introduce the new discover, Formula: C18H27N3O4.

IMIDAZOLE DERIVATIVES .8. STEREOSELECTIVE FORMATION OF 1-[(E)3-(1-IMIDAZOLYL)-2-ALKENOYL]IMIDAZOLES

The reaction of propynoic, 2-butynoic, and 3-butynoic acids with 1,1′-carbonyldiimidazole stereoselectively provides the corresponding 1-[(E) 3-(1-imidazolyl)-2-alkenoyl]imidazoles.

The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 3543-74-6 is helpful to your research. Formula: C18H27N3O4.