Tag: M.W=200-300

Some common heterocyclic compound, 150058-27-8, name is Methyl 2-ethoxy-1H-benzo[d]imidazole-7-carboxylate, molecular formula is C11H12N2O3, 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. Quality Control of Methyl 2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

To a solution of methyl 2-ethoxy-lH-benzo[d]imidazole-7-carboxylate (1.00 g, 4.54 mmol) in 2-propanol (15 ml) was added potassium carbonate (1.26 g, 9.08 mmol) and this was stirred at 30°C for 5 minutes. To this mixture were added 2-(4- (bromomethyl)phenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (1.44 g, 4.77 mmol) and tetrabutylammonium iodide (0.084 g, 0.227 mmol) and the temperature was increased to 45°C. After stirring for 2.5 hours, another portion of 2-(4-(bromomethyl)phenyl)-4,4,5,5- tetramethyl-l,3,2-dioxaborolane (0.250 g, 0.842 mmol) was added and the reaction was stirred for an additional 18 hours. The reaction was cooled to RT and diluted with EtOAc (200 ml), and 0 (50 ml) was added. The layers were separated and the organic layer was washed with brine (50 ml), then dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure. The residue was dissolved in DCM (10 ml) and injected on a 40-gram ISCO-type silica gel column pre-equilibrated with hexane and the title compound was purified by elution using a 0 to 60percent EtOAc/hexane gradient to provide the title compound as a yellow solid. (1.44 g, 3.31 mmol, 72percent yield). LC-MS (Method H): 1.42 min, [M + H]+= 437.2; H NMR (400 MHz, CDC13) delta ppm 7.73 (dd, 7=8.0, 1.0 Hz, 1 H) 7.67 (m, 7=8.2 Hz, 2 H) 7.53 (dd, 7=7.8, 1.2 Hz, 1 H) 7.16 (t, 7=7.8 Hz, 1 H) 6.96 (m, 7=8.2 Hz, 2 H) 5.63 (s, 2 H) 4.65 (q, 7=7.0 Hz, 2 H) 3.72 (s, 3 H) 1.46 (t, 7=7.0 Hz, 3 H) 1.31 (s, 12 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 150058-27-8, its application will become more common.

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

Application of 641571-11-1, 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 641571-11-1 as follows.

4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid (100 g, 0.326 mole) and 5-(4-methyl- IH-imidazol-1-yl)-3-(trifluoromethyl)benzenamine (78.75 g, 0.326 mole) were stirred in N-methyl pyrrolidone (700 ml) at 55-60C. Thionyl chloride (83 ml, 0.978 mole) was added and the temperature of the reaction mass was raised to 75C and stirred for 6 hours. The reaction masswas cooled to 40-45C, and water (500 ml) was added. The reaction mass was cooled to 20-25C and acetone (3000 ml) was added. The reaction mass was further stirred for 12 hours. The solid was isolated by filtration and washed with acetone to obtain nilotinib base.Yield :- 200 g

According to the analysis of related databases, 641571-11-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CIPLA LIMITED; KING, Lawrence; RAO, Dharmaraj Ramachandra; MALHOTRA, Geena; PATHI, Srinivas Laxminarayan; CHINIMILLI, Venugopalarao; GANGRADE, Manish Gopaldas; (21 pag.)WO2016/151304; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route 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

Synthetic Route of 918321-20-7, These common heterocyclic compound, 918321-20-7, name is Methyl 5-amino-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-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.

In an inertized (N2) reaction vessel at internal temperature 20C and under exclusion of humidity and air, Compound 1 (1.0 eq.) and Compound 2 (1.2 eq.) are reacted in the presence of cesium carbonate (2.4 eq.), tris(dibenzylidenaceton) dipalladium(O) (0.035 eq.) and Xantphos (0.07 eq.) in a mixture of toluene and 1 ,4-dioxane at internal temperature of 99C. After 8 hours, the mixture is cooled to internal temperature of 60C. Subsequently, dimethylformamide (DMF), filter aid (CEFOK) and activated charcoal (EKNS) are added, and the mixture is stirred and cooled to internal temperature of 35 C. The solids are filtered off and washed with a mixture of dimethylformamide and toluene. To the filtrate, which contains the product Compound 3, is introduced at internal temperature of25 C hydrogen chloride gas (CLC) whereupon the HQ salt of Compound 3 crystallizes. The palladium residue mainly remains in solution. After warming to 60 C and cooling to 0C, the solids are filtered using a centrifuge and are washed with a mixture of toluene and dimethylformamide. The damp Compound 3 HC1 salt is charged to a reactor (equipped with pH probe) together with dimethylformamide and is heated to 60C. By adding a 4 wt% of aqueous tripotassium phosphate solution, the pH is adjusted to a pH range of 6.8-7.6 (with a target of pH 7.2) while Compound 3 crystallizes as free base. After cooling to 22C and stirring, the solids are filtered using a centrifuge and are washed with drinking water. The moist solids are dried at 50 C under vacuum to give dry, crude Compound 3. In order to remove residual palladium, dry, crude Compound 3 is dissolved in dimethylformamide at internal temperature of 60C and stirred together with Smopex-234 (commercially available from Johnson Matthey) and activated charcoal for 90 minutes. The solids are filtered off at internal temperature of 60C and are washed with dimethylformamide. To the filtrate are added drinking water and Compound 3 seed crystals. More drinking water is added while Compound 3 crystallizes. After cooling to internal temperature of 20 C, the solids are filtered using a centrifuge and are washed with a mixture of deionized water and dimethylformamide and with deionized water. The moist solids are dried at 50C under vacuum, providing 6-(4-Bromo-2-fluorophenylamino)-7-fluoro-3- methyl-3H-benzoimidazole-5-carboxylic acid methyl ester (Compound 3).

The synthetic route of 918321-20-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; ARRAY BIOPHARMA INC.; KRELL, Christoph, Max; MISUN, Marian; NIEDERER, Daniel, Andreas; PACHINGER, Werner, Heinz; WOLF, Marie-christine; ZIMMERMANN, Daniel; LIU, Weidong; STENGEL, Peter, J.; NICHOLS, Paul; WO2014/63024; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 641571-11-1, 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 641571-11-1 as follows.

Method II; To a flask was added 6-methyl-5-[4-(pyrid-3-yl)pyrimid-2-ylamino) nicotinic acid (30.7 g) and SOCl2 (500 mL) and the reaction mixture was refluxed for 4 hours. The reaction mixture was concentrated under reduced pressure to give a solid, which is used for the next step directly. To the above acid chloride was added a clear solution of 3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline (24.1 g) in pyridine (200 mL) and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and then the residue was added with chloroform (500 mL) and water (500 mL) and extracted. The organic phase was dried, filtrated, concentrated, and purified through column chromatography to give the titled compound.

According to the analysis of related databases, 641571-11-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Sun, Piaoyang; EP1840122; (2007); A1;,
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. Application In Synthesis of 1H-imidazol-2-amine sulfate(2:1)

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;,
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. 2963-77-1, name is 4-(1H-Benzo[d]imidazol-2-yl)aniline, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 4-(1H-Benzo[d]imidazol-2-yl)aniline

General procedure: The mixture of 0.1mol of phenoxy acetic acid derivative(PAA1-PAA5) and 0.1mol of dicyclohexyl carbodiimide in10 mL dichloromethane was stirred at room temperature.After 30 minutes, a solution of AB or APB in 20 ml of dichloromethaneand 5 ml of pyridine was added. The reactionmixture was stirred initially at 0C for 2 h followed by stirring at room temperature for 12 h. The precipitated dicyclohexylureawas removed by filtration and the solvent wasdistilled at reduced pressure on rotary vacuum evaporator.The dried product was dissolved in ethyl acetate (10 mL) andthe solution was washed with 10% aqueous solution of sodiumbicarbonate followed by distilled water to remove thetraces of residual dicyclohexylurea. The ethyl acetate layerwas dried with anhydrous magnesium sulphate and then solventwas distilled off to obtain the crude product which wasrecrystallized from ethanol-water mixture.

According to the analysis of related databases, 2963-77-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Singh, Gurmeet; Bansal, Yogita; Bansal, Gulshan; Goel, Rajesh Kumar; Medicinal Chemistry; vol. 10; 4; (2014); p. 418 – 425;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 144689-93-0, These common heterocyclic compound, 144689-93-0, name is Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-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.

EXAMPLE 15 Ethyl 1-[(2′-t-butoxycarbonylbiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate (Compound No. 1-119) Following a procedure similar to that described in Example 1(a), but using 0.845 g of ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate (prepared as described in Preparation 9) and 1.22 g of t-butyl 4′-bromomethylbiphenyl-2-carboxylate, 1.31 g of the title compound were obtained as a gum. This compound was allowed to stand at room temperature, which caused it to crystallize. It was then recrystallized from a mixture of diisopropyl ether and hexane, to give pure title compound, melting at 90-91 C. Nuclear Magnetic Resonance Spectrum (CDCl3) delta ppm: 0.97 (3H, triplet, J=7 Hz); 1.23 (3H, triplet, J=7 Hz); 1.25 (9H, singlet); 1.60 (6H, singlet); 1.82 (2H, sextet, J=7 Hz); 2.67 (2H, triplet, J=7 Hz); 4.24 (2H, quartet, J=7 Hz); 5.51 (2H, singlet); 5.72 (1H, singlet); 6.87-7.85 (8H, multiplet).

Statistics shows that Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate is playing an increasingly important role. we look forward to future research findings about 144689-93-0.

Reference:
Patent; Sankyo Company, Limited; US5616599; (1997); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application 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.

Aqueous hydrogen peroxide (30%, 18.9 mL) was added drop-wise over 20 minutes to a solution of 3-methoxy-4-(4-methyl-1/-/-imidazol-1-yl)benzaldehyde (5.0 g, 20.0 mmol) and potassium hydroxide (6.1 g, 92.5 mmol) in MeOH (38 mL) and water (6.6 mL) at 65 C. Following completion of the addition the reaction was stirred at room temperature for an additional 25 minutes. The reaction was then allowed to cool to room temperature and was acidified with cone. HCI. The resulting precipitate was filtered to provide the title compound as a white solid. Yield: 4.6 g, 17.1 mmol, 74%. MS (APCI) m/z 232.9 (M+1 ). 1H NMR (400 MHz, CD3OD) 2.45 (br s, 3H), 4.00 (s, 3H), 7.65 (br s, 1 H), 7.67 (d, J=8.4 Hz, 1 H), 7.82 (dd, J=8.3, 1.6 Hz, 1 H), 7.89 (d, J=1.6 Hz, 1 H), 9.24 (d, J=1.6 Hz, 1 H).

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; PFIZER INC.; ALLEN, Martin, Patrick; AM ENDE, Christopher, William; BRODNEY, Michael, Aaron; DOUNAY, Amy, Beth; JOHNSON, Douglas, Scott; PETTERSSON, Martin, Youngjin; SCHWARZ, Jacob, Bradley; TRAN, Tuan, Phong; WO2010/100606; (2010); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 144689-93-0, A common heterocyclic compound, 144689-93-0, name is Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate, molecular formula is C12H20N2O3, 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 1; Preparation of olmesartan medoxomilTo dimethyl acetamide (300 ml) was added 4-(1-hydroxy-1-methylethyl)-2-propyl imidazol- 5-carboxylic acid ethyl ester (50 gms) and powdered sodium hydroxide (26 gms). To this, 4-[2-(trityltetrazol-5-yl)phenyl]benzyl bromide (135 gms) was charged at 45-500C. The contents were stirred for 5 hours at 45-500C. Diisopropylethyl amine (100 ml) was charged to the reaction mass at 40-450C. A solution of 5-methyl-2-oxo-1 , 3-dioxane-4-yl)methyl chloride (80 gms) diluted with dimethyl acetamide (160 ml) was slowly added to the reaction mass at 40-450C over a period of 1 hour. The contents were heated to 60-650C and maintained for 4 hours. The reaction mass was then cooled to 30-350C and neutralized with concentrated hydrochloride acid. The reaction mass was filtered to remove inorganic impurities, charcoalized using charcoal (10 gms) andstirred for 30 minutes at 40-450C. The reaction mass was filtered over hyflo. The clear filtrate was acidified with hydrochloric acid (100 ml) slowly at 25-30C. The contents were stirred at 60C for 1 hour. The reaction mass was chilled to 0-5C and filtered to remove tritanol. The reaction mass was concentrated under reduced pressure. The residue was quenched with water (500ml), neutralized with base and extracted in dichloromethane (500 ml). The clear dichloromethane extract was then concentrated under reduced pressure and stripped off with acetone. The residue thus obtained was isolated from acetone (250 ml) to give 55 gms of the title compound. Chromatographic purity- > 99%

The synthetic route of 144689-93-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CIPLA LIMITED; CURTIS, Philip, Anthony; WO2008/43996; (2008); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem