Category: imidazoles-derivatives

Electric Literature of 96797-15-8, 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. 96797-15-8 name is 4-Iodo-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.

To a solution of 4-IODO-L-TRITYL-LH- imidazole (15.0 g, 34 mmoles) in THF (150 ml) at room temperature was added ethylmagnesium bromide (41 ml, 40.7 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (5.6 g, 40.7 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (RIPHENYLPHOSPHINE) palladium (4.0 g, 3.43 mmoles) and 5-bromo-2-methylpyridine (7.0 g, 40.7 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with an EDTA buffer (at APPROIMATE pH 9) (2x 300 ML), NACI (sat. ) (300 ml), dried over sodium sulfate, filtered, and concentrated. The crude product was dissolved in ethanol (250 ml) and concentrated HCl (13.6 ml) was added to the solution at room temperature. The reaction mixture was heated in a 50C oil bath for 2 hours. Upon cooling, the reaction was filtered and washed with ethyl ether (25 ml) to yield 5- (1H- imidazol-4-yl) -2-methyl-pyridine (5.815g, 63%). MH+ (160).

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

Reference:
Patent; CHIRON CORPORATION; WO2004/96823; (2004); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. Application In Synthesis of 1H-Imidazole

(a) A solution of alpha-bromo-4-toluonitrile (86.6 g) in dichloromethane (1000 mL) is mixed with imidazole (68.0 g). The mixture is stirred at ambient temperature for 15 hours and then diluted with water (1000 mL). Any undissolved solid is removed by filtration and the separated organic solution is then repeatedly washed with water (5*200 mL) to remove excess imidazole, and then dried (MgSO4). The crude product obtained upon evaporation of the solvent can be purified by trituration with cold diethyl ether (200 mL) to obtain 4-(1-imidazolylmethyl)-benzonitrile, m.p. 99-101; HCl salt, m.p. 142-144.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 288-32-4, its application will become more common.

Reference:
Patent; Ciba-Geigy Corporation; US4749713; (1988); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 41806-40-0, 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. 41806-40-0 name is 1-Methylimidazole-5-carboxylic Acid, 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.

EXAMPLE 72 (METHOD T); N-r4-(6,6-Dimethyl-4-oxo-4,5,6,7-tetrahvdrori.31thiazolor5.4-clpyridin-2-yl)-3,4- dihvdro-2H- 1 ,4-benzoxazin-6-yl]- 1 -methyl-lH-imidazole-5-carboxamide; To a stirred solution of Example 42 (0.025 g, 0.08 mmol) in DCM (1 mL) were added l-methylimidazol-5-ylcarboxylic acid (0.013 g, 0.10 mmol), DIPEA (0.02 mL, 0.10 mmol), EDC (0.030 g, 0.16 mmol) and HOBT (0.05 g, 0.04 mmol). The reaction mixture was stirred at r.t. for 18 h, then concentrated in vacuo. Purification by preparative HPLC (Method 6) gave the title compound (0.01 g, 29%) as a yellow oil. 6H (CDCl3) 9.25 (IH, s), 8.46-8.43 (IH, m), 7.33 (IH, dd, J8.9 and 2.4 Hz), 7.07 (IH, d, J 0.9 Hz), 7.02 (IH, d, J0.8 Hz), 6.94 (IH, d, J 8.9 Hz), 5.56 (IH, br. s), 4.36-4.29 (2H, m), 4.16-4.09 (2H, m), 4.11 (3H, s), 2.90 (2H, s), 1.40 (6H, s). LCMS (ES+) 439.4 (M+H)+, RT 2.69 minutes (Method 1).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Methylimidazole-5-carboxylic Acid, and friends who are interested can also refer to it.

Reference:
Patent; UCB PHARMA S.A.; WO2008/1076; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 3314-30-5, 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 3314-30-5 as follows.

General procedure: A suspension of methyl 2-(2-aminoethyl)-1 ,3-thiazole-4-carboxylate (5) (1.96 g, 10.52 mmol), 1 H- benzimidazole-2-carbaldehyde (2.31 g, 15.79 mmol) and DIPEA (1.83 ml, 10.52 mmol) in MeOH (100 ml) was stirred at room temperature for 12 h. The reaction mixture was cooled to 0°C, NaBH4 (0.597 g, 15.79 mmol) was added and the mixture stirred at room temperature for 2 h. The reaction mixture was concentrated in vacuo and the residue dissolved in EtOAc (100 ml) and washed with saturated NC03 (2 x 50 ml). The combined aqueous layers were extracted with EtOAc (3 x 50 ml) and the combined organic layers dried (MgS04), filtered and evaporated in vacuo. Purification by flash column chromatography (KP- NH, eluting with a gradient of 0-10percent MeOH / DCM) afforded the title compound (1.4 g, 38percent, 90percent purity) as a tan solid. 1 H-NMR (Methanol-d4, 250 MHz): d[ppm]= 8.27 (s, 1 H), 7.60 – 7.49 (m, 2H), 7.29 – 7.17 (m, 2H), 4.09 (s, 2H), 3.92 (s, 3H), 3.26 (t, J = 6.3 Hz, 2H), 3.10 (t, J = 6.8 Hz, 2H) HPLCMS (Method A): [m/z]: 317 [M+H]+In a similar fashion to general procedure 3, 2-(2-aminoethyl)-5-chloro-N-[(3-fluoropyridin-2-yl)methyl]-1 ,3- thiazole-4-carboxamide dihydrochloride (192) (143 mg, 0.37 mmol), 1 H-1 ,3-benzodiazole-2-carbaldehyde (70.1 mg, 0.48 mmol), MgS04 (200 mg) in MeOH (10 ml) at room temperature for 3 d, followed by addition of NaBH4 (28 mg, 0.74 mmol) gave the title compound (94 mg, 56percent) as a white solid after purification by prep-HPLC. 1 H-NMR (DMSO-d6, 500 MHz): d[ppm]= 12.19 (s, 1 H), 8.71 (t, J = 5.6 Hz, 1 H), 8.37 (dt, J = 4.6, 1.3 Hz, 1 H), 7.70 (ddd, J = 10.0, 8.4, 1.1 Hz, 1 H), 7.54 (d, J = 7.2 Hz, 1 H), 7.45 (d, J = 7.0 Hz, 1 H), 7.40 (dt, J = 8.6, 4.4 Hz, 1 H), 7.14 (t, J = 7.5 Hz, 2H), 4.66 – 4.58 (m, 2H), 3.97 (s, 2H), 3.12 (t, J = 6.3 Hz, 2H), 2.94 (t, J = 6.3 Hz, 2H) HPLCMS (Method A): [m/z]: 445.1 [M+H]+

According to the analysis of related databases, 3314-30-5, the application of this compound in the production field has become more and more popular.

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

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 16681-56-4 as follows. Computed Properties of C3H3BrN2

Obtained in Example 50 (a) (S) -1-tert- butoxycarbonylamino-4- (5-chloro-7- (4,4,5,5-dioxa -1,3,2- borane-2-yl)benzoxazol-2-yl) -3-methyl piperazine (48 mg, 0.1mmol), 2- bromo -1H- imidazole (29 mg, 2.0 eq.), Tetrakis(triphenylphosphine) palladium (0) (11.6 mg, 0.1 eq), potassium carbonate (55 mg, 4.0 equiv) 1, 4-dioxane (800muL) and water (200muL) for dissolution, and under an argon atmosphere in an oil bath from 110 4 hours with stirring did. Water was added to the reaction mixture, the product extracted with ethyl acetate, an organic layer was washed with saturated aqueous sodium chloride. The organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by preparative TLC (developing solvent, methanol: chloroform = 1: 19) to give the title compound 21.3 mg.

According to the analysis of related databases, 16681-56-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MeijiSeika Pharma Corporation; Kikuchi, Jika; Tabata, Yuji; Yamakawa, Takeru; Matsuhira, Takashi; Watanabe, Naoko; Kuboda, Natsuki; Kaneda, Kaoru; (143 pag.)KR2016/30503; (2016); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 28890-99-5, These common heterocyclic compound, 28890-99-5, name is 5H-Benzo[d]benzo[4,5]imidazo[1,2-a]imidazole, 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.

[28890-99-5] (3.0 g, 14.4 mmol) is dissolved in THF (0204) (100 ml) and the suspension is cooled to 0 C. NaH as 60% suspension (691 mg, 17.3 mmol) is added in portions. [98-59-9] is dissolved in THF (50 ml) and the solution is dropped into the reaction mixture. It is stirred over night at room temperature. Saturated NH4CI solution (150 ml) is slowly added. It is extracted with ethyl acetate. The crude product is used without further purification.

The synthetic route of 28890-99-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK PATENT GMBH; STENGEL, Ilona; MAIER-FLAIG, Florian; HARBACH, Philipp; MONTENEGRO, Elvira; LUDEMANN, Aurelie; (0 pag.)WO2019/170691; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 615-16-7, These common heterocyclic compound, 615-16-7, name is 2-Hydroxybenzimidazole, 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.

To a stirred solution of compound 114 (1 g, 7.46 mmol) in CH2C12 (10 mL) under argon atmosphere was added chlorosulfonic acid (1 mL, 14.92 mmol) at 0 C; heated to reflux and stirred for 16 h. The reaction was monitored by TLC; after completion of the reaction, the volatiles were removed in vacuo and the residue diluted with water (10 mL); neutralized with aqueous NaOH solution and extracted with EtOAc (3 x 20 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to afford compound 115 (980 mg, 58%) as an off-white solid. TLC: 10% MeOH/ CH2C12 (Rf. 0.5); 1H-NMR (DMSO-i/tf, 400 MHz): delta 10.66 (s, 1H), 10.61 (s, 1H), 7.24 (d, J= 6.4 Hz, 1H), 7.18 (s, 1H), 6.85 (d, J = 8.4 Hz, 1H).

The synthetic route of 615-16-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION; ARNOLD, Lee Daniel; MAAG, Hans; TURNER, JR., William W.; (274 pag.)WO2016/168619; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 36947-68-9, 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. 36947-68-9, name is 2-Isopropyl-1H-imidazole belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: A mixture of corresponding 2-chloro-N-phenylacetamide (1 mmol), imidazole (1.5 mmol), N,N-diisopropylethylamine (0.35 ml, 2 mmol) in dimethylformamide (7mL) was stirred for 16 hours at 60C. Then the reaction mixture was cooled to roomtemperature and treated with water (35 ml). The crude product was filtered andpurified by recrystallization from acetonitrile or by HPLC chromatography (methanol/water). Yield: 15-70 % depending on the structures of the starting materials.

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-Isopropyl-1H-imidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; SPRINGER, Wolfdieter; FIESEL, Fabienne C.; CAULFIELD, Thomas R.; (172 pag.)WO2018/23029; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 1632-83-3, name is 1-Methylbenzimidazole, 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 1632-83-3, Formula: C8H8N2

1-methylbenzimidazole (1 mmol, 132.1 mg)Perfluoroiodobutane (1.1 mmol, 380.5 mg) was placed in a 10 mL round bottom flask.Potassium tert-butoxide (1.2 mmol, 134.7 mg) is addedAnd 5mL of toluene,Stir at room temperature for 3 hours,TLC monitored the endpoint of the reaction.After the toluene was removed by rotary evaporation, the mixture was washed with water and extracted with dichloromethane. The organic phase was collected and dried. The dichloromethane was removed by rotary evaporation to give a crude product.The crude product was subjected to silica gel column chromatography with petroleum ether and ethyl acetate as eluents (ratio by volume = 15:1).2-Iodo-1-methylbenzimidazole was obtained (white solid, 208.9 mg, yield 81%).

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; Liaoning University; Liang Fushun; Liu Xia; Han Zhengbo; Su Zhongmin; (10 pag.)CN107501023; (2017); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 305790-48-1,Some common heterocyclic compound, 305790-48-1, name is 6-Bromo-1-methyl-1H-benzo[d]imidazol-2(3H)-one, molecular formula is C8H7BrN2O, 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 5-bromo-3-methyl-1H-benzimidazol-2-one (4.90 g, 21.6 mmol, Intermediate IP) in THF (300 mL) was added t-BuOK (3.63 g, 32.3 mmol) at 0 C. The mixture was stirred at 0-10 C. for 1 hour under N2. Then a solution of [1-[(4-methoxyphenyl) methyl]-2,6-dioxo-3-piperidyl] trifluoromethanesulfonate (9.87 g, 25.9 mmol) in THF (100 mL) was added to the reaction mixture at 0-10 C. during 30 minutes. The mixture was stirred at 0-10 C. for 30 minutes under N2. An additional solution of [1-[(4-methoxyphenyl) methyl]-2,6-dioxo-3-piperidyl]trifluoromethanesulfonate (2.47 g, 6.47 mmol) in THF (20 mL) was added to the reaction mixture at 0-10 C. dropwise. The mixture was then stirred at 0-10 C. for another 30 minutes under N2. On completion, the reaction was quenched water (400 mL) and extracted with EA (3×200 mL). The combined organic layer was concentrated in vacuo. The residue was triturated with EA (80 mL) and filtered. The filter cake was collected and dried in vacuo to give the title compound (6.70 g, 67% yield) as light yellow solid. The filtrate was also concentrated in vacuo and the residue was purified by column chromatography to give another batch title compound (1.80 g, 18% yield) as light yellow solid. 1H NMR (400 MHz, DMSO-d6) delta 7.47 (d, J=1.6 Hz, 1H), 7.21-7.16 (m, 3H), 7.01 (d, J=8.0 Hz, 1H), 6.85 (d, J=8.8 Hz, 2H), 5.55-5.51 (m, 1H), 4.84-4.73 (m, 2H), 3.72 (s, 3H), 3.33 (s, 3H), 3.04-3.00 (m, 1H), 2.83-2.67 (m, 2H), 2.07-2.05 (m, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6-Bromo-1-methyl-1H-benzo[d]imidazol-2(3H)-one, its application will become more common.

Reference:
Patent; Kymera Therapeutics, Inc.; Mainolfi, Nello; Ji, Nan; Kluge, Arthur F.; Weiss, Matthew M.; Zhang, Yi; (1443 pag.)US2019/192668; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem