Category: imidazoles-derivatives

51605-32-4, A common heterocyclic compound, 51605-32-4, name is Ethyl 5-methyl-1H-imidazole-4-carboxylate, molecular formula is C7H10N2O2, 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.

Ethyl 2-bromo-4-methyl-1H-imidazole-5-carboxylate (EV-AT8648-001)? Step 1 To a stirred solution of ethyl 4-methyl-1H-imidazole-5-carboxylate (CAS 51605-32- 4, 500 mg, 3.24 mmol) in acetonitrile (10 ml) and chloroform (10 ml) was added N- bromosuccinimide (577 mg, 3.24 mmol) and the reaction stirred under a nitrogen atmosphere at room temperature for 18h. The reaction mixture was concentrated and the residue was purified by flash column chromatography (10-100percent ethyl acetate/heptane) to afford 560 mg (73percent) of ethyl 2-bromo-4-methyl-1H-imidazole-5-carboxylate (EV-AT8648-001) as an off-white solid. LCMS (method D): retention time 0.87 min, M/z = 233/235 (M + 1).

The synthetic route of 51605-32-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PADLOCK THERAPEUTICS, INC.; DEVRAJ, Rajesh; KUMARAVEL, Gnanasambandam; ATTON, Holly; BEAUMONT, Edward; GADOULEAU, Elise; GLEAVE, Laura; KERRY, Philip Stephen; LECCI, Cristina; MENICONI, Mirco; MONCK, Nat; PALFREY, Jordan; PAPADOPOULOS, Kostas; TYE, Heather; WOODS, Philip A.; (158 pag.)WO2017/147102; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 41716-18-1, name is 1-Methyl-1H-imidazole-4-carboxylic acid, molecular formula is C5H6N2O2, 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. 41716-18-1

Preparation of Compound 69aAt 0¡ã C., a suspension of 1-methyl-1H-imidazole-4-carboxylic acid (100.9 mg, 0.8 mmol) in CH2Cl2 (8 mL) was added oxalylchloride (305 mg, 0.21 mL, 2.4 mmol) followed by addition of 1 drop of DMF. The mixture was stirred for 2 days at 25¡ã C. All solvent was removed in vacuo to give a crude 69a.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 41716-18-1, its application will become more common.

Reference:
Patent; Pfizer Inc.; US2009/318440; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1546-79-8, 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 1546-79-8 as follows.

5-[4-Fluoro-5-(4-bromophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-2-pyridinesulfonamide (Step 2) To a solution of 1-(4-bromophenyl)-2-fluoro-1-ethanone (3.54 g, 16.3 mmol) in tetrahydrofuran (50 ml) was added dropwise 1M lithium hexamethyldisilazide tetrahydrofuran solution (19.6 ml, 19.6 mmol) at -78 C. After stirring for 45 min., N-trifluoroacetylimidazole (2.3 ml, 19.6 mmol) was added. The resulting mixture was allowed to warm up to room temperature and stirred for 1.5 hr. The mixture was acidified with 2M hydrochloric acid and extracted with diethyl ether (300 ml). The separated organic layer was washed with water (100 ml*3) and dried over magnesium sulfate. The solution was evaporated to give 5.2 g of 1-(4-bromophenyl)-2,4,4,4-tetrafluoro-1,3-butanedione as a brown oil.

According to the analysis of related databases, 1546-79-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PFIZER INC.; US2003/144280; (2003); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1615-14-1, Adding a certain compound to certain chemical reactions, such as: 1615-14-1, name is 2-(1H-Imidazol-1-yl)ethanol, 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 1615-14-1.

A 50-mL three-necked, round-bottomed flask, equipped with thermometer, nitrogen inlet, addition funnel, magnetic stirrer and reflux condenser was flame dried and flushed with nitrogen. The flask was charged with 25 ml_ of anhydrous dichloromethane. Freshly distilled 1-ethanol imidazole (1, 0.01 mol) was added into the flask. The flask was chilled with ice-water bath and benzyl chloride (0.011 mol) in 15 ml_ of anhydrous dichloromethane was added cautiously into the flask with continous stirring over 20 minutes. The solution was heated under reflux for 5 hours and then allowed to cool to room temperature. The dichloromethane solvent was distilled under to give 92% of 3-benzyl-1-ethanol imidazolium chloride 5.

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, 2-(1H-Imidazol-1-yl)ethanol, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MIMOS BERHAD; AHMAD, Mohd Rais; WO2010/33014; (2010); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. 1849-01-0 name is 1-Methyl-1H-benzo[d]imidazol-2(3H)-one, 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. 1849-01-0

Step A: 5-(3-Methyl-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-thiazolidine-2,4-dione (I-51). To a solution of 1-methyl-1,3-dihydro-benzoimidazol-2-one (300 mg, 1.13 mmol) in DMF (4.0 mL) was added NaH (60% in mineral oil, 101.7 mg, 3.39 mmol) at 0 oC under nitrogen. The reaction mixture was stirred at 0 oC under N2 for 30 minutes. Then 5-bromo-thiazolidine-2,4- dione (230 mg, 1.13 mmol) in DMF (1 mL) was added slowly. After stirring at r.t. for 10 minutes, the reaction was quenched with water (30 mL) and extracted with EtOAc (50 mL x 3). The combined organic layer was washed with brine and dried over Na2SO4. The mixture was filtered and the filtrate solvent was removed under reduced pressure. The residue was purified via silica gel column chromatography (Petroleum ether/EtOAc) to give the title compound (22 mg, 7.4% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) delta ppm: 12.7 (s, 1H), 7.76-7.13 (m, 5H), 3.34 (s, 3H). LC-MS: Calculated exact mass = 263.0; Found [M+H]+ = 263.9.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Methyl-1H-benzo[d]imidazol-2(3H)-one, and friends who are interested can also refer to it.

Reference:
Patent; KYMERA THERAPEUTICS, INC.; MAINOLFI, Nello; JI, Nan; KLUGE, Arthur F.; (282 pag.)WO2019/140387; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

496-46-8, Adding some certain compound to certain chemical reactions, such as: 496-46-8, name is Tetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-dione, 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 496-46-8.

14.2 g (100 mmol) of glycoluril,16.0 g (400 mmol) of sodium hydroxide and 140 mL of dimethylsulfoxide were mixed,After heating and stirring at 40 C. for 1 hour, And 34.4 g (400 mmol) of allyl chloride were added dropwise at the same temperature over 20 minutes, and the mixture was heated and stirred at 40 C. for 2 hours to complete the reaction.The resulting reaction mixture was evaporated to dryness under reduced pressure, and the obtained dry solid was separated and extracted with 400 mL of ethyl acetate and 400 mL of water, and the ethyl acetate layer was washed with 100 mL of water, then with 100 mL of saturated brine, Dried over sodium sulfate, and ethyl acetate was distilled off under reduced pressure to obtain 27.4 g of 1,3,4,6-tetraallyl glycoluril as a colorless oil, yield 90%.

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 496-46-8.

Reference:
Patent; Shikoku Chemicals Co., Ltd.; Takeda, Takuma; Kashihara, Takashi; Kumano, Noboru; Mizobe, Noboru; (59 pag.)JP2015/59101; (2015); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

15965-54-5, 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 15965-54-5 as follows.

General procedure: A mixture of 10 (5 mM), 11 (5 mM) in DMF (20 mL) containing K2CO3 (2 mM) and TBAB (2 mM) was stirred at RT for a period of 3-5 h. The reaction was monitored by TLC analysis. After the completion of reaction, the mixture was poured into ice-cold water (30 mL). The separated solid was filtered, washed with water (2 9 10 mL) and dried. The crude product was recrystallized from a suitable solvent to yield pure 9.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 15965-54-5, and friends who are interested can also refer to it.

Reference:
Article; Srikrishna, Devulapally; Dubey, Pramod Kumar; Research on Chemical Intermediates; vol. 44; 7; (2018); p. 4455 – 4468;,
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. 641571-11-1, name is 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline, This compound has unique chemical properties. The synthetic route is as follows., 641571-11-1

To a solution of 2- (5-ethoxy-6-oxo-1 6-dihydropyridin-3-yl) -4 6-dimethylpyrimidine-5-carboxylic acid (150 mg 0.519 mmol) 3- (4-methyl-1H-imidazol-1-yl) -5- (trifluoromethyl) aniline (125 mg 0.519 mmol) and Et3N (79 mg 0.778 mmol) in 1 4-dioxane (5 mL) stirred under N2at 20 was added DPPA (171 mg 0.622 mmol) in one charge. The reaction mixture was heated to 80 for 1 hr. Then the solution was concentrated. The residue was purified by preparative HPLC (Instrument DC/Column ASB C18 150*25mm/Mobile phase A Water+0.1HCl/Mobile phase BMeCN /Flowrate 25 mL/min /Gradient Profile Description 15-55 (B) ) to yield a off white solid of 1- (2- (5-ethoxy-6-oxo-1 6-dihydropyridin-3-yl) -4 6-dimethylpyrimidin-5-yl) -3- (3- (4-methyl-1H-imidazol-1-yl) -5- (trifluoromethyl) phenyl) urea dihydrochloride (11.53 mg 3.67) . TLC (DCM/MeOH 51 Rf 0.4) 1HNMR(400 MHz CD3OD) delta9.44-9.40 (m 1H) 8.27-8.23 (m 1H) 8.20 (s 1H) 7.92 (s 2H) 7.84 (s 1H) 7.69 (s 1H) 4.17 (d J 6.8 Hz 2H) 2.57 (s 6H) 2.44 (s 3H) 1.48 (t J 6.9 Hz 3H) ES-LCMS m/z 528.2 (M+H)

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; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; GLAXOSMITHKLINE (CHINA) R & D COMPANY LIMITED; CHEUNG, Mui; DEMARTINO, Michael P.; EIDAM, Hilary Schenck; GUAN, Huiping Amy; QIN, Donghui; WU, Chengde; GONG, Zhen; YANG, Haiying; YU, Haiyu; ZHANG, Zhiliu; (391 pag.)WO2016/37578; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 1849-01-0, name is 1-Methyl-1H-benzo[d]imidazol-2(3H)-one, 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 1849-01-0, 1849-01-0

To a stirred solution of l-methyl-2,3-dihydro-lH-l,3-benzodiazol-2-one (217 mg, 1.46 mmol) in DMF (2 mL) was added NaH (64.5 mg, 1.61 mmol, 60% w/w dispersed into mineral oil) at 0 C under nitrogen atmosphere. The reaction mixture was stirred for 20 min at 0 C. To the above mixture was added dropwise a solution of 3-bromopiperidine-2,6-dione(140.6 mg, 0.73 mmol) in DMF (0.5 mL) at 0 C. The resulting mixture was stirred for additional 3 hours at room temperature. The resulting mixture was quenched with AcOH (0.5 mL) and was concentrated under reduced pressure. The crude product was purified by prep-HPLC with the following conditions: Column: XBridge Shield RP18 EVO Column, 5 um, 19 x 150 mm; Mobile Phase A: water (plus 0.05% FA), Mobile Phase B: ACN; Flow rate: 20 mL/min; Gradient: 10% B to 35% B in 7 min; Detector: UV 220 nm; Rt: 6.30 min. Desired fractions were collected and concentrated under reduced pressure. The residue was lyophilized to afford 3-(3-methyl-2-oxo-2,3-dihydro-lH- l,3-benzodiazol-l-yl)piperidine-2,6-dione, 1-2, as a white solid (30.4 mg, 21%): NMR (400 MHz, OMSO-d6) delta 11.03 (br s, 1H), 7.13 – 6.97 (m, 4H), 5.30 (dd, J= 12.7, 5.4 Hz, 1H), 3.35 (s, 3H), 2.90 – 2.78 (m, 1H), 2.73 – 2.49 (m, 2H), 2.03 – 1.90 (m, 1H); LC/MS (ESI, m/z): [(M + 1)]+ = 260.2.

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-1H-benzo[d]imidazol-2(3H)-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; KYMERA THERAPEUTICS, INC.; MAINOLFI, Nello; JI, Nan; ZHANG, Yi; WEISS, Matthew M.; (223 pag.)WO2019/60693; (2019); 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. 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