Month: September 2021

Reference of 1457-58-5,Some common heterocyclic compound, 1457-58-5, name is 2-Methyl-1H-imidazole-5-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.

Scheme 96. The imidazole-acid (2 g, 12.3 mmol) was taken up in 4 M HCI in dioxane (10 mL) and EtOH (120 mL) and heated at 90 0C for 18 h. The solution was concentrated. The residue was partitioned between EtOAc and sat. NaHCO3 (aq.). The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine and dried (MgSO4). The solution was filtered which provided 1.2 g (63 %) of the imidazole-ester as a white solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Methyl-1H-imidazole-5-carboxylic acid, its application will become more common.

Reference:
Patent; SCHERING CORPORATION; WO2009/5646; (2009); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 705-09-9, These common heterocyclic compound, 705-09-9, name is 2-(Difluoromethyl)-1H-benzo[d]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.

Step 1 : To a solution of 3a in DMF was added NaH with ice-bath. The resulting mixture was stirred for 15min. at 0-5 0C and was added 1g. The reaction mixture was stirred at r.t. over night and evaporated to remove DMF. The residue was purified by column chromatography (PE:EA=1:2) to give 3b.

Statistics shows that 2-(Difluoromethyl)-1H-benzo[d]imidazole is playing an increasingly important role. we look forward to future research findings about 705-09-9.

Reference:
Patent; TYROGENEX, INC.; LIANG, Congxin; LI, Zhigang; WO2010/56320; (2010); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. Formula: C11H12N2O3

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 129378-52-5,Some common heterocyclic compound, 129378-52-5, name is 2-(tert-Butyldimethylsilyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide, molecular formula is C11H23N3O2SSi, 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.

Intermediate 26: 4(5)-Chloro-1 H-imidazoleHO. alphaTo a solution of 2-[(1 ,1-dimethylethyl)(dimethyl)silyl]-N,N-dimethyl-1 H-imidazole-1- sulfonamide (for preparation see US2005075366,15 g, 51.8 mmol) in dry THF (100 ml_), under nitrogen and at -7O0C, a 1.6M solution of butyllithium in hexane (34.0 ml_, 54.4 mmol) was slowly added. The temperature was allowed to reach -550C in 1 hour then cooled down to -780C and dimethylsulfamoyl chloride (8.33 ml_, 78 mmol) was slowly added and the mixture was stirred at -780C for 30min and at 2O0C for 2 hours. The solvents were removed by evaporation and the residue was stirred with 2M HCI solution (100ml) for 12 hour at room temperature. Complete deprotection of the nitrogen was achieved while partial TBDMS deprotection was observed. The aqueous acid solution was basified with KOH pellets and the aqueous phase was extracted with EtOAc. The organic phases were dried over Na2SO4 and evaporated under reduced pressure. The crude residue was treated with a 1 M solution of TBAF in THF (51.8 ml_, 51.8 mmol) and heated to 6O0C for 2 hours. The volatiles were removed under vacuo and the residue was chromatographed to give the title compound (3.5 g, 34.1 mmol); UPLC/MS Rt=O.33 min; m/z (ES): 103 and 105 [M+H]+; 1H NMR (CDCI3): delta 7.00 (d, 1 H), 7.57 (d, 1 H), 11.54 (brs, 1 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(tert-Butyldimethylsilyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide, its application will become more common.

Reference:
Patent; GLAXO GROUP LIMITED; DI FABIO, Romano; GIANOTTI, Massimo; LESLIE, Colin Philip; STASI, Luigi Piero; WO2010/142652; (2010); 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. 17325-26-7, name is Methyl 1H-imidazole-5-carboxylate, A new synthetic method of this compound is introduced below., SDS of cas: 17325-26-7

(1) To a solution of methyl 4-imidazole carboxylate (a-1) (5.0 g, 39 mmol) in tetrahydrofuran (THF) (100 mL), p-trifluoromethyl benzyl alcohol (a-2) (6.5 mL, 48 mmol) and triphenylphosphine (PPh3) (12 g, 47 mmol) were added and after adding a toluene solution (25 mL, 48 mmol) of 1.9 mol/L diisopropyl azodicarboxylate (DIAD) dropwise, the resulting mixture was stirred at room temperature for 3 hours. After distilling off the solvents under reduced pressure, the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=50:500:100) and purified again by silica gel (NH) column chromatography (n-hexane:ethyl acetate=90:1050:50) to give methyl 1-[4-(trifluoromethyl)benzyl]-1H-imidazole-5-carboxylate (a-3) (amount, 7.7 g; yield, 69%).

The synthetic route of 17325-26-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KAKEN PHARMACEUTICAL CO., LTD.; IKEGAMI, Satoru; WATANABE, Atsushi; HIRANO, Kimio; OHYAMA, Tadashi; (56 pag.)US2016/130232; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 137049-00-4, 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 137049-00-4 as follows.

To a solution of 2-chloro-1-(1 /-/-indol-3-yl)-2-phenylethanone (0.200 g; 0.741 mmol) in DMF (5 mL) cooled to 0 C was added sodium hydride (60% dispersion in mineral oil; 0.053 g; 1.333 mmol). The reaction mixture was stirred at room temperature for 0.5 h. 1-Methyl-1 H- imidazole-4-sulfonyl chloride (0.268 g; 1.484 mmol) and DMAP (0.005 g; 0.037 mmol) were added and the reaction mixture was stirred at room temperature for 3 h. Water was added and the reaction mixture was extracted with ethyl acetate. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel using a gradient of ethyl acetate (30% to 100%) in heptane furnished 0.301 g (98%) of 2-chloro-1-(1-((1-methyl-1 /-/-imidazol-4-yl)sulfonyl)-1 H-indol- 3-yl)-2-phenylethanone as a solid. ESI/APCI(+): 414 (M+H); 436 (M+Na). ESI/APCI(-): 412 (M- H).

According to the analysis of related databases, 137049-00-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; KATHOLIEKE UNIVERSITEIT LEUVEN; BARDIOT, Dorothee; CARLENS, Gunter; DALLMEIER, Kai; KAPTEIN, Suzanne; McNAUGHTON, Michael; MARCHAND, Arnaud; NEYTS, Johan; SMETS, Wim; WO2013/45516; (2013); 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. 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