Author: Jessica.F

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. 131020-36-5, name is Methyl 1-methyl-1H-benzo[d]imidazole-5-carboxylate, A new synthetic method of this compound is introduced below., Formula: C10H10N2O2

1-METHYL-1H-BENZOIMIDAZOLE-5-CARBOXYLIC ACID : H20 (100 mL) was added to a solution of methyl 1-METHYL-1H-BENZOIMIDAZOLE-5-CARBOXYLATE (10.00 g, 52.6 MMOL) in 1 N LiOMe in MEOH (100 mL, 100 MMOL). The resulting solution was stirred under an inert atmosphere and monitored to completion BY 1H NMR.Aqueous 1 N HCI (100 mL, 100 MMOL) was added dropwise to the reaction mixture cooled with an ice-water bath. The gray solid which formed was collected by filtration and washed with water followed with methanol. Vacuum drying afforded 8.60 g of desired PRODUCT.1H NMR (300 MHZ, D6-DMSO) B 12.75 (br s, 1 H), 8.31 (s, 1 H), 8.23 (s, 1 H), 7.89 (d, J=8.36 Hz, 1 H), 7.62 (d, J=8.35 Hz, 1 H), 3.85 (s, 3 H).

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; PHARMACIA CORPORATION; WO2004/99131; (2004); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 22884-10-2, name is 2-(1H-Imidazol-1-yl)acetic 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. 22884-10-2

Example 1; [0022] An oven-dried 250 ml_ 4-neck RB flask was fitted with a mechanic stirrer, K-thermocouple, condenser, nitrogen inlet and outlet and two 1/8 inch polytetrafluoroethylene (PTFE) feeding lines. The system was flushed with nitrogen for 30 minutes. Under nitrogen protection, imidazoIe-1-ylacetic acid (15.97 g, 0.13 mole), sulfolane (70 ml_) and phosphorous acid (2.67 g, 0.033 mol) were charged to the RB flask. The reaction mixture was mixed at 210 RPM and heated to 600C. PCI3 (9.18 g, 0.067mol) was added slowly (1.3 mL/mn) via a masterflex tubing pump. Five minutes were allowed for mixing. Alternately fed were 26 wt% phosphorous acid sulfolane solution (30.7 g, 10.23 g each addition at 1.6 mL/min) and PCI3 (27.5 g, 9.18 g each portion at 1.3 mL/min). Three to five minutes of mixing were allowed between additions. The addition took 1 hr 3 min and temperature was maintained between 600C and 670C. After addition was complete, the temperature of the reaction mixture was raised to 800C and was held at this temperature for 4 hours. Then the temperature of the reaction mixture was raised to 880C and held for 30 minutes. Ambient temperature water (50 g) was added in to quench the reaction. The solution was refluxed for 3 hrs . temperature, the product was vacuum-filtered and rinsed with 38 g of acetone. Zoledronic acid was obtained as a white crystalline solid (24.1 g, 95.3wt% purity by quantitative NMR, 65% yield). Example 2; [0023] An oven-dried 250 mL 4-neck RB flask was fitted with a mechanic stirrer, K-thermocouple, condenser, nitrogen inlet and outlet and two 1/8 inch PTFE feeding lines. The system was flushed with nitrogen for 30 minutes. Under nitrogen protection, imidazole-1-ylacetic acid (15.97 g, 0.13 mole), sulfolane (70 mL) and phosphorous acid (2.67 g, 0.033 mol) were charged to the RB flask. The reaction mixture was mixed at 300 RPM and heated to 600C. PCI3 (9.18 g, 0.067mol) was added in slowly (1.3 mL/min) via a masterflex tubing pump. Five minutes were allowed for mixing. Alternately fed were 26 wt% phosphorous acid sulfolane solution (30.7 g, 10.23 g each addition at 1.6 mL/min) and PCI3 (27.5 g, 9.18 g each portion at 1.3 mL/min. Three to five minutes of mixing were allowed between additions. The addition took 1 hr 6 min and temperature was maintained between 54 and 64C. After addition was complete, the temperature of the reaction mixture was raised to 800C and held for 4 hours. Then the temperature of the reaction mixture was raised to 880C and held for 30 minutes. This slurry was transferred via 3/8″ PTFE tubing using nitrogen pressure into 100 mL of pre-heated (80C) water under mixing. The resultant water solution was heated to refluxing and held at that temperature for 4 hr. It was then slowly cooled to room temperature then to 1-2C and held for 1.5 hr at this temperature. The product was collected via vacuum filtration. The cake was rinsed with acetone (20 g) and zoledronic acid was obtained as a white crystalline solid (19.1 g, 98.3 wt% purity by quantitative NMR, 53% yield). Example 3; [0024] An oven-dried 250 mL 4-neck RB flask was fitted with a mechanic stirrer, K-thermocouple, condenser, nitrogen inlet and outlet and two 1/8 inch PTFE feeding lines. The system was flushed with nitrogen for 30 minutes. Under nitrogen protection, imidazole-1-ylacetic acid (15.9 g, 0.13 mole), sulfolane (70 mL) and phosphorous acid (2.67 g, 0.033 mol) were charged to the RB flask. The reaction mixture was mixed and heated to 6O0C. PCI3 (36.7 g, 0.267 mol) and phosphorous acid (8.0 g, 0.098 mol) in – . mL/min respectively. Reaction temperature remained between 6O0C and 67C during feeding, After addition of PCI3 and phosphorous acid, the reaction slurry was heated to 800C and held at that temperature for 4 hours. This slurry was then transferred via 3/8″ PTFE tubing using nitrogen pressure into 50 m._ of pre-heated (8O0C) water under mixing. The resultant water solution was heated to refluxing and held at that temperature for 4 hr. It was then slowly cooled to 48-500C. Acetone (200 ml_) was added in slowly and then it was cooled to 1-2C and held for 2 hr at this temperature. The product was collected via vacuum filtration. The cake was rinsed with acetone (35 g) and zoledronic acid was obtained as a white crystalline solid (22.1 g, 98.6 wt% purity by quantitative NMR, 61 % yield). Example 4; [0025] A 2.5 L resin-kettle was fitted with a mechanic stirrer, K-thermocouple, condenser, nitrogen inlet and outlet, two 1/8 inch PTFE tubing as PCI3 and phosphorous acid sulfolane solution feeding lines. The system was dried under a stream of nitrogen. Under nitrogen, imidazoleacetic acid (79.92 g, 0.63 mol), phosphorous acid (13.90 g, 0.17 mol) and sulfolane (350 ml_) were added to the resin-kettle and mixed at 200 RPM. The mixture was heated to 62C then PCI3 (36.7 g, 0.267 mol) was added in slowly (1.3 mL/min) using a masterflex tubing pump. The slurry was mixed for 5 minutes. Phosphoro…

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 22884-10-2, its application will become more common.

Reference:
Patent; ALBEMARLE CORPORATION; WO2008/157050; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 60-56-0, 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. 60-56-0 name is 1-Methyl-1H-imidazole-2(3H)-thione, 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.

General procedure: A mixture of 3-chloromethyl-4-methoxybenzaldehyde (2a) (1.85 g, 0.01 mol), the corresponding phenol or thiol (0.011 mol), and potassium carbonate (2.00 g, 0.0145 mol) in a mixture of acetonitrile-DMF (20 mL, from 9 : 1 to 8 : 2, v/v) was refluxed for 5-7 h withstirring (TLC monitoring). After evaporation of the solvents, the residue was treated with water, a precipitate formed was filtered off, washed with 40% aqueous ethanol, and dried in air. Yields and physicochemical characteristics of aldehydes 5a-m and 6a-g are given in Table 2.

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

Reference:
Article; Khachatryan; Razinov; Kolotaev; Belus?; Matevosyan; Russian Chemical Bulletin; vol. 64; 2; (2015); p. 395 – 404; Izv. Akad. Nauk, Ser. Khim.; 2; (2015); p. 395 – 404,10;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 288-32-4, name is 1H-Imidazole, 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 288-32-4, HPLC of Formula: C3H4N2

In a wide-necked Erlenmeyer flask areintroduced 6.8g (0.1 mol) imidazole, 45.5g (0.1 mol)1-bromohexadecan, 2.4g (7.5mmol)tertiobutyllammoniumbromid (TBAB). The mixtureis adsorbed on mixture of potassium carbonate andpotassium hydroxide ratio 1:1 and then irradiatedin an open vessel in a domestic microwave oven300 Watt power for 3 min by period of 20 secondstill it changed to pasty.After dilution in dichloromethane followedby washing with water, the organic phase isseparated and dried over sodium sulfate. Afterfiltration, the solvent is evaporated under vacuum.

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

Reference:
Article; Djellal, Ahmed; Amirat, Samia; Oriental Journal of Chemistry; vol. 31; 4; (2015); p. 2391 – 2394;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

These common heterocyclic compound, 2403-66-9, name is 3-(1H-Benzo[d]imidazol-2-yl)propan-1-ol, 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. category: imidazoles-derivatives

6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methyl-2-methylsulfonyl-pyrimidin-4-amine F5 (480 mg, 1.384mmol) and 3-(1H-benzimidazol-2-yl)propan-1-ol (244 mg, 1.38 mmol) were placed in a 20 mL vial and dissolved in THF(5 mL). AIM solution of NaHMDS in THF (1.38 mL, 1.38 mmol) was added, and the reaction was stirred overnight.Solvent was then removed, and the product was purified by silica gel flash column chromatography (EtOAc/hexanesgradient). 500 mg (82%) of F6 were isolated as an off-white foam. 1H NMR delta (300 MHz, DMSO-d6): 7.84-7.80 (1 H, m),7.76 (2 H, dd, J = 6.20, 3.18 Hz), 7.51 (2 H, dd, J = 6.28, 3.15 Hz), 4.46 (2 H, d, J = 5.76 Hz), 4.37-4.31 (2 H, m), 2.54(4H, s), 2.46 (3 H, s), 2.29 (3 H, s), 1.99 (3 H, s). HRMS (Electrospray): m/z 443.1413 (MH+).

The synthetic route of 3-(1H-Benzo[d]imidazol-2-yl)propan-1-ol has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Merck Sharp & Dohme Corp.; COX, Christopher; RAHEEM, Izzat, T.; SHIPE, William, D.; THEBERGE, Cory, R.; (62 pag.)EP2621276; (2017); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products 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

33468-69-8, Adding some certain compound to certain chemical reactions, such as: 33468-69-8, name is 4-(Trifluoromethyl)-1H-imidazole, 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 33468-69-8.

To 100 mg (0.36 mmol) of (S)-5-(4-fluoro-3-(trifluoromethyl)phenyl)-6-methyl-3,6-dihydro- 2H-1,3,4-oxadiazin-2-one (Intermediate 75) and 73 mg of 4-trifluoromethyl imidazole (0.54 mmol) dissolved in 2 mL of DMF was added 235 mg of powdered Cs2C03 (0.72 mmol) and the mixture was heated at 80 Patent; BAYER AKTIENGESELLSCHAFT; BAYER PHARMA AKTIENGESELLSCHAFT; THE BROAD INSTITUTE, INC.; DANA-FARBER CANCER INSTITUTE, INC.; ELLERMANN, Manuel; GRADL, Stefan, Nikolaus; KOPITZ, Charlotte, Christine; LANGE, Martin; TERSTEEGEN, Adrian; LIENAU, Philip; HEGELE-HARTUNG, Christa; SUeLZLE, Detlev; LEWIS, Timothy, A.; GREULICH, Heidi; WU, Xiaoyun; MEYERSON, Matthew; BURGIN, Alex; (500 pag.)WO2019/25562; (2019); 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. 5465-29-2, name is 2-Propylbenzimidazole, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 5465-29-2

[Example 1] (E)-[2-(2-Propylbenzimidazol-1-yl)methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene]acetonitrile (compound 1) (E)-2-(2-Bromomethyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)acetonitrile (648 mg, 2.00 mmol) obtained in Reference Example B1 and 2-propylbenzimidazole (385 mg, 2.40 mmol) were dissolved in DMA (2 mL), potassium carbonate (553 mg, 4.00 mmol) was added, and the mixture was stirred at room temperature for 14 hr. Water was added to the mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=97/3) to give the title compound (compound 1) (778 mg, 96%). ESI-MS m/z: 404 (M + H)+; 1H-NMR (CDCl3, delta): 1.01 (t, J = 7.4 Hz, 3H), 1.85-1.90 (m, 2H), 2.79 (t, J= 7.6 Hz, 2H), 3.06 (br s, 4H), 5.29 (s, 2H), 5.67 (s, 1H), 6.79-6.88 (m, 2H), 7.11-7.35 (m, 7H), 7.43 (dd, J = 7.3, 1.7 Hz, 1H), 7.76 (d, J = 7.3 Hz, 1H).

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 5465-29-2.

Reference:
Patent; Kyowa Hakko Kirin Co., Ltd.; EP2327690; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 4857-06-1, The chemical industry reduces the impact on the environment during synthesis 4857-06-1, name is 2-Chloro-1H-benzo[d]imidazole, I believe this compound will play a more active role in future production and life.

Example 32-5 Synthesis of 1-((2-(trimethylsilyl)ethoxy)methyl)-2-chloro-1H-benzo[d]imidazole General Method XE To a solution of 2-chloro-1H-benzo[d]imidazole (1 g, 6.6 mmol.) in dry DMF (10 mL) was added sodium hydride (60%, 0.26 g, 6.5 mmol.) at room temperature under nitrogen atmosphere. 2-(trimethylsilyl)ethoxymethyl chloride (SEMCl, 1.14 g, 6.8 mmol.) was added dropwise after the solution stirred for 1.5 h. The resulting mixture stirred overnight and then quenched with water and extracted with ethyl acetate (30 mL*3). The combined organic layers was washed with water, dried over sodium sulfate and concentrated to give a residue. The residue was purified by column chromatography to give 1-((2-(trimethylsilyl)ethoxy)methyl)-2-chloro-1H-benzo[d]imidazole (1.13 g, 60.8%).

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-Chloro-1H-benzo[d]imidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; InterMune, Inc.; US2009/269305; (2009); 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. 616-47-7, name is 1-Methyl-1H-imidazole, A new synthetic method of this compound is introduced below., Product Details of 616-47-7

1-methylimidazole (1 mmol, 82.1 mg),Perfluoro iodobutane (3.1 mmol, 1072 mg) was placed in a 10 mL round bottom flask.Potassium tert-butoxide (2.2 mmol, 246.9 mg) was addedAnd 5mL of toluene, stirring 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).The product 1 was obtained: 2-iodo-1-methylimidazole (white solid, 72 mg, 35%).Product 2: 2,5-diiodo-1-methylimidazole (white solid, 210 mg, 63%)

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