Month: June 2021

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. 1849-02-1, name is 2-Chloro-1-methyl-1H-benzo[d]imidazole, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 1849-02-1

EXAMPLE 39; CYCLOHEXYL-ETHYL- {2- [4- (1-METHYL-1 H-BENZOIMIDAZOL-2-YLOXY)-PHENYL]-ETHYL}- amine; A mixture of 4- [2- (cyclohexyl-ethyl-amino)-ethyl]-phenol (247 mg, 1.0 MMOL), N- methyl benzimidazole (EXAMPLE 8 ; 200 mg, 1.2 MMOL), and CS2CO3 (652 mg, 2.0 MMOL) in DMF (3 mL) was stirred at 100 C for 16 h. The reaction mixture was cooled and filtered through diatomaceous earth, which was then washed with ethyl acetate (30 mL). The combined filtrates were washed with H20 (3 x 10 mL) then brine (10 mL), dried (NA2SO4), filtered, and concentrated under reduced pressure. The crude material was purified on SI02 (10 g; 0-100% 10% [2 M NH3 in CH30H] in CH2CI2/CH2C12) to provide 105 mg (28% yield) of a brown oil. MS (ESI) : mass calculated for C24H3INSO, 377.53 ; M/Z FOUND, 378.4 [M+H] +. H NMR (400 MHz, CDC13) : 7.52 (d, J =7. 2, 1 H), 7.63-7. 58 (m, 1 H), 7.33-7. 18 (m, 7H), 3.75 (s, 3H), 2.81-2. 70, m, 4H), 2.68 (q, J = 7.1, 2H), 2.60- 2.50 (m, 1H), 1. 90-1. 80 (m, 4H), 1.67 (d, J : = 12.3, 1 H), 1.35-1. 18 (m, 4H), 1.15-1. 05 (m, 1H), 1.12 (t, J=7. 1, 3H)

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 1849-02-1.

Reference:
Patent; JANSSEN PHARMACEUTICA N.V.; WO2005/12296; (2005); 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. 641571-11-1, name is 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline, A new synthetic method of this compound is introduced below., Application In Synthesis of 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline

Example 1[51] Synthesis of 4-methyl-N-[3-(4-methylimidazole-l-yl)-5-trifluoromethyl-phenyl] -3-(4-thiazole-2-yl-pyrimidine-2-yl amino)benzamide [52][53] Method A[54] In a reactor, potassium tert-butoxide (20.9g, 186.56mmol) was dissolved in tetrahydrofuran (167ml), and then was cooled to -20+50C. To the resultant product, 3-(4-methyl-imidazole-l-yl)-5-trifluoromethyl-phenylamine (1Og, 41.46mmol) dissolved in tetrahydrofuran (80ml) was added and stirred for 30 minutes. When the stirring was completed, 4-methyl-3-(4-thiazole-2-yl-pyrimidine-2-yl amino)benzoic acid ethyl ester (15.5g, 45.60mmol) dissolved in tetrahydrofuran (90ml) was slowly added to the resultant product. After the addition, the temperature of the mixture was slowly elevated to room temperature, and stirring was carried out until the reaction was completed. When the reaction was completed, the reaction mixture was cooled to 5-1O0C, and then 15% sodium chloride aqueous solution (337ml) was slowly added to the reaction mixture. After the addition, the temperature of the reaction mixture was slowly elevated to room temperature again, and then water (170ml) was added thereto and an organic layer was extracted and separated.[55] To the organic layer, ethyl acetate (400ml) was added. Then, the layer was washed with water (200ml), separated and was subjected to vacuum concentration. When the concentration was completed, methanol (220ml) was added thereto. Then, the resultant layer was subjected to reflux- stirring for 1 hour, cooled to room temperature, and then stirred for 2 hours.[56] The obtained solid was filtered, sufficiently washed with methanol (100ml), and then dried to provide a pale yellow solid final compound (17.51g, yield 81%).[57] 1H-NMR(DMSOd6, delta= 2.19(s,3H), 2.36(s,3H), 7.24(s,lH), 7.35(m,2H), 7.47 (s,lH),7.64(d,lH), 7.71(d,lH), 7.92(d,lH), 8.01(s,lH), 8.11(s,lH), 8.30(s,2H), 8.47(d,lH), 9.00(s, IH), 10.49(s,lH)

The synthetic route of 641571-11-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; IL-YANG PHARM. CO., LTD.; KIM, Dong Yeon; CHO, Dae Jin; LEE, Gong Yeal; KIM, Hong Youb; WOO, Seok Hun; WO2010/18895; (2010); 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 24134-09-6 as follows. COA of Formula: C5H7BrN2

n-BuLi (2.66 M in hexanes, 0.963 mL, 2.56 mmol) was added dropwise to a stirred slurry of 5-bromo-1,2-dimethyl-1H-imidazole (470 mg, 2.68 mmol) in THF (7 mL) at ?-70 C. under argon. After stirring for another 7 minutes, the slurry was treated dropwise over 5 minutes with a solution of methyl 4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline-6-carboxylate (500 mg, 1.22 mmol, Intermediate 75) in THF (6 mL). The reaction was stirred in the dry ice/acetone bath for another 10 minutes, then removed from the cold bath and stirred for 6 minutes, then stirred in an ice bath for 2 minutes, then quenched with 5 M aqueous NH4Cl (0.77 mL, 3.85 mmol) to give an orange solution. The reaction mixture was dried (Na2SO4), filtered, and concentrated to dryness. The residue was purified by silica flash column chromatography (0-10% MeOH/DCM) to provide the title compound.

According to the analysis of related databases, 24134-09-6, the application of this compound in the production field has become more and more popular.

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; Cummings, Maxwell D.; Jones, William Moore; Goldberg, Steven; US2015/105366; (2015); 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. 131020-36-5, name is Methyl 1-methyl-1H-benzo[d]imidazole-5-carboxylate belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. Application In Synthesis of Methyl 1-methyl-1H-benzo[d]imidazole-5-carboxylate

The methyl 1-methyl-1H-benzimidazole-5-carbonate (500 mg) obtained above was dissolved in methanol (10 ml). 1 N Sodium hydroxide solution (8 ml) was added thereto, and the mixture was stirred for 4 hours at room temperature. Water was added to the reaction mixture which was then acidified by formic acid. Precipitates were collected by filtration and dried under reduced pressure to give the title compound (367 mg, Y.: 79%). 1H NMR; (DMSO-d6) delta (ppm): 3.8 (s, 3H), 7.6 (d, 1H), 7.8 (dd, 1H), 8.2 (d, 1H), 8.3 (s, 1H).

The synthetic route of 131020-36-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SANWA KAGAKU KENKYUSHO CO., LTD.; EP1595866; (2005); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 103057-10-9, 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. 103057-10-9 name is 4-(Chloromethyl)-1-trityl-1H-imidazole, 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.

REFERENCE EXAMPLE 34 Ethyl 5,6-Dimethoxy-1-(1-trityl-4-imidazolyl)methyl-1H-indazole-3-carboxylate In 5000 ml of dimethyl sulfoxide was suspended 250.2 g of ethyl 5,6-dimethoxyindazole-3-carboxylate, and 40.2 g of lithium methoxide was added to the suspension, followed by stirring at room temperature for 1 hour. A solution of 447.8 g of 4-chloromethyl-1-tritylimidazole in 2000 ml of dimethyl sulfoxide was added dropwise thereto at room temperature over 10 minutes. After stirring at room temperature for 2 hours, 4.2 g of lithium methoxide and 44.8 g of 4-chloromethyl-1-tritylimidazole were further added thereto, followed by stirring at room temperature for 1 hour. The reaction mixture was poured into 30000 ml of ice-water while stirring. A precipitated crystal was collected, washed with three 2000 ml portions of water, and dried. The solid was dissolved in 10000 ml of chloroform, and the solution was dried over sodium sulfate, filtered, and the solvent was evaporated. The residue was purified by silica gel column chromatography (chloroform:ethanol=50:1) and recrystallized from chloroform/isopropyl alcohol to yield 222.0 g of the title compound as a colorless prism crystal. Melting point: 184-186 C.; IR (KBr) cm-1: 1704, 1496, 1268, 1146, 1132, 1092, 748, 700; 1 H-NMR (CDCl3) delta ppm: 1.21 (6H, d, J=5.9 Hz, Me of iso-PrOH), 1.46 (3H, t, J=7.3 Hz), 3.93 (3H, s), 3.97 (3H, s), 4.01 (1H, m, CH of iso-PrOH), 4.49 (2H, q, J=7.3 Hz), 5.61 (2H, s), 6.79 (1H, s), 7.03 (5H, m), 7.13 (1H, s), 7.28 (10H, m), 7.47 (1H, s), 7.51 (1H, s); Elementary analysis for C35 H32 N4 O4.C3 H8 O: Calcd. (%): C 72.13; H 6.37; N 8.85; Found (%): C 71.53; H 6.37; N 8.70.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-(Chloromethyl)-1-trityl-1H-imidazole, and friends who are interested can also refer to it.

Reference:
Patent; Daiichi Pharmaceutical Co., Ltd.; US5681954; (1997); A;,
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 3034-41-1 as follows. name: 1-Methyl-4-nitroimidazole

To the suspension of 1-methyl-4-nitro-1H-imidazole (128 mg, 1.012 mmol) in ethanol (5 mL) 5% palladium on carbon (10 mg, 0.053 mmol) was added. The reaction mixture was degassed under reduced pressure and stirred under hydrogen atmosphere at roomtemperature for 3 hours. The reaction mixture was filtered over celite layer and washed with ethanol. The filtrate was concentrated under reduced pressure, dissolved in toluene, transferred to a Schlenk flask and again concentrated under reduced pressure. 4-(5-Chloro- 3 -(4-chloro-2-fluorobenzyl)-2-methylpyrazolo [1, 5-a]pirymidyn-7-yl)morpholine obtained in Example 1, Step F (200 mg, 0.506 mmol), tris(dibenzylideneacetone)dipalladium(0)(23.2 mg, 0.025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphine)xanthene (29,3 mg, 0,05 1 mmol) and sodium carbonate (107 mg, 1.012 mmol) were added and the mixture was degassed under reduced pressure. Under argon atmosphere degassed toluene (5 mL) was added and the mixture was purged with argon for 15 minutes. Reaction mixture was heated to 100 C for 24 hours. The mixture was cooled to room temperature, diluted with ethylacetate (10 mL), filtered through celite layer and washed with ethyl acetate (25 mL). The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silicagel, eluent: AcOEt 100% to AcOEt:methanol = 9:1, v/v). The product was hot-crystallized from AcOEt:heptan to obtain white crystals with a yield of 27% (63 mg, 0.138 mmol).

According to the analysis of related databases, 3034-41-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CELON PHARMA S.A.; MROCZKIEWICZ, Michal; LIPNER, Joanna; GUNERKA, Pawel; DUBIEL, Krzysztof; WIECZOREK, Maciej; ZDZALIK, Daria; STANCZAK, Aleksandra; LAMPARSKA-PRZYBYSZ, Monika; STYPIK, Bartosz; WO2015/118434; (2015); 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. 152628-03-0, name is 4-Methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 152628-03-0

A suspension of 2 (2.18 g, 10 mmol) in thionyl chloride (20 mL, 276 mmol) was refluxed for 2 h, and then the excess thionyl chloride was removed under a vacuum to provide the crude acid chloride (3) as an off-white solid. The crude product 3 was used in the next step without further purification.

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 152628-03-0.

Reference:
Article; Zhang, Jun; Wang, Jin-Liang; Zhou, Zhi-Ming; Li, Zhi-Huai; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, Xiao-Feng; Fei, Fan; Liu, Ting; Liang, Ai-Hua; Bioorganic and Medicinal Chemistry; vol. 20; 14; (2012); p. 4208 – 4216;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 144690-33-5,Some common heterocyclic compound, 144690-33-5, name is Ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-((2′-(1-trityl-1H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylate, molecular formula is C45H44N6O3, 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%; Example 2Preparation of olmesartan medoxomilTo dimethyl acetamide (600 ml) was added 4-(1-hydroxy-1-methylethyl)-2-propyl imidazol- 5-carboxylic acid ethyl ester (100 gms) and powdered potassium hydroxide (50 gms). To this was charged 4-[2-(trityltetrazol-5-yl)phenyl]benzyl bromide (270 gms) at 45-50C. The contents were stirred for 5 hours at 45-50C. Diisopropylethyl amine (200 ml) was charged to the reaction mass at 40-450C. To this was slowly added a solution of 5-methyl-2-oxo- 1 ,3-dioxane-4-yl)methyl chloride (160 gms) diluted with dimethyl acetamide (320 ml) at 40- 45C 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 was neutralized with concentrated hydrochloride acid. The reaction mass was filtered to remove inorganic impurities. The reaction mass was charcoalized using charcoal (20 gms) and was stirred for 30 minutes at 40-450C. The reaction mass was filtered over hyflo. The clear filtrate was acidified with hydrochloric acid (200 ml) slowly at 25-300C. The contents were stirred at 60C for 1 hour. The reaction mass was chilled to 0-50C and was filtered to remove tritanol. The reaction mass was concentrated under reduced pressure. The residue was quenched with water (1000 ml), neutralized with base and extracted in dichloromethane (1000 ml). The clear dichloromethane extract was then concentrated under reduced pressure, stripped off with acetone. The residue thus obtained was isolated from the acetone (500 ml) to give 110 gms of the title compound. Chromatogrphic purity- > 99%; Example 4Preparation of trityl 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 potassium hydroxide (25 gms). To this was charged 4-[2-(trityltetrazol-5-yl)phenyl]benzyl bromide (135 gms) at 45-500C. The contents were stirred for 5 hours at 45-500C. Diisopropylethyl amine (100 ml) was charged to the reaction mass at 40-45C. To this was slowly added a solution of 5-methyl-2-oxo- 1 ,3-dioxane-4-yl) methyl chloride (80 gms) diluted with dimethyl acetamide (160 ml) at 40- 45C 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 was neutralized with concentrated hydrochloride acid. The reaction mass was filtered to remove inorganics. The reaction mass was charcoalized using charcoal (10 gms) and was stirred for 30 minutes at 40-450C. The reaction mass was filtered over hyflo. The clear filtrate was quenched with purified water(200 ml)at 25-30C over a period of 3-4 hours. The contents were stirred at 25-300C for 30 minutes. Crude trityl olmesartan medoxomil was isolated by filtration, slurried in water (500 ml), centrifuged and dried under reduced pressure at 45-50C.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-((2′-(1-trityl-1H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylate, its application will become more common.

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

Reference of 144689-93-0,Some common heterocyclic compound, 144689-93-0, name is Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate, molecular formula is C12H20N2O3, 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: 3-(4-Bromo-benzyl)-5-(1-hydroxy-1-methyl-ethyl)-2-propyl-3H-imidazol-4-carboxylic acid ethyl ester (IV; X=Br) NaH (228 mg, 9.53 mmol), previously placed under N2 atmosphere and washed with pentane to remove paraffin, is reacted at 0C with a solution of a compound of formula (IX), wherein R4 is ethyl (1.76 g, 7.33 mmol), dissolved in DMF (5 mL). 10 minutes after the addition, a solution of a compound of formula (X), wherein X=Z=Br (2.02 g, 8.06 mmol) in DMF (10 mL) is added thereto. The mixture is left under stirring for 1 hour, then diluted with ethyl acetate and water. The organic phase is separated, dried and evaporated to a residue. The crude is subjected to purification by flash chromatography with a 50 mm diameter column, eluding with a hexane/ethyl acetate 1:1 mixture. 2.15 g of the title compound are obtained; yield: 45%. 1H-NMR (CDCl3) 0.96 (3H, t, J=7.4 Hz) 1.18 (3H, t, J=7.1 Hz) 1.65 (6H, s) 1.70 (2H, sx, J=7.5 Hz) 2.62 (2H, t, J=7.7 Hz) 4.23 (2H, q, J=7.1 Hz) 5.41 (2H, s) 5.76 (1H, s) 6.81 (2H, d, J=8.3 Hz) 7.46 (2H, d, J=8.3 Hz).

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

Reference:
Patent; Dipharma Francis S.r.l.; EP1905770; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 570-22-9, name is 1H-Imidazole-4,5-dicarboxylic acid, 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 570-22-9, Safety of 1H-Imidazole-4,5-dicarboxylic acid

100 ml of methanol was added into 1H-imidazole-4,5-dicarboxylic acid (10 g, 64 mmol, 1 eq), and then the mixture was cooled to -9 C. in a low temperature cooler and added with thionyl chloride (5 to 10 eq). The mixture was then heated gradually to a reflux temperature and refluxed with stirring over-night, until it turned from a white turbid solution into a colorless transparent liquid. The solvent was then removed from the mixture by a rotary evaporator with a water pump in a water bath of 40 C. and thereby a white solid was obtained. The solid was washed with a dilute aqueous solution of sodium hydroxide and dried in an oven at 40 C. to obtain a product (dimethyl 1H-imidazole-4,5-dicarboxylate). 1HNMR (DMSO, 500 MHz): delta 8.057 (1H,s), delta 3.815 (6H,s).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1H-Imidazole-4,5-dicarboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; GUANGZHOU INSIGHTER BIOTECHNOLOGY CO.,LTD.; PENG, Xianfeng; QIN, Zonghua; (15 pag.)US2018/370921; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem