Tag: M.W=100-200

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. 26663-77-4, name is Methyl benzimidazole-5-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Safety of Methyl benzimidazole-5-carboxylate

To a solution of methyl 1H-benzo[d]imidazole-5-carboxylate (0.90 g, 5.1 mmol) in DMF(20 ml) was added NaH (0.25 g, 6.2 mmol), and the reaction mixture was stirred at room temperature for 30 mm. Then (2-(chloromethoxy)ethyl)trimethylsilane (0.94 g, 5.6 mmol) wasadded and the reaction mixture was stirred at room temperature for 2 hours. When LCMS showed that the reaction completed, the reaction mixture was diluted with EtOAc (100 mL), washed with H20 (100 mL x 2) and brine (100 mL), dried over Na2504 and concentrated under reduced pressure to afford crude product as an oil, which was purified by column chromatography on silica gel (eluted with petroleum ether/EtOAc = 1:1) to afford mixture ofmethyl 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-benzo[d]imidazole-5-carboxylate and methyl 1- ((2-(trimethylsilyl)ethoxy) methyl)- 1 H-benzo [d] imidazole-6-carboxylate as an oil. LC/MS (m/z): 307 (M+H).To a solution of LiA1H4 (0.30 g, 7.8 mmol) in THF (20 ml) was added solution of Step A product (1.2 g, 3.9 mmol) in THF (30 mL) at 0C, the reaction mixture was allowed to warm to room temperature and stirred for 3 hours. When TLC showed that the reaction completed, the reaction mixture was quenched with sat. aq. NH4C1 (50 mL) and the mixture was filteredthrough a pad of celite. The filtrate was extracted with EtOAc (100 mL), washed with H20 (100 mL) and brine (100 mL), dried over Na2504 and concentrated under reduced pressure to afford mixture of (1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-benzo [d] imidazol-5-yl) methanol and (1- ((2-(trimethylsilyl)ethoxy)methyl)- 1 H-benzo[d]imidazol-6-yl)methanol as an oil, which was used in next step without further purification. ?H NMR (CDC13, 400 MHz) oe 8.03 (s, 1H), 8.02(s, 1H), 7.86-7.79 (m, 2H), 7.64 (s, 1H), 7.61-7.55 (m, 1H), 7.43 (d, J= 7.3 Hz, 1H), 7.36 (d, J=8.4 Hz, 1H), 5.59 (s, 4H), 4.90 (s, 2H), 4.87 (s, 2H), 3.59-3.53 (m, 4H), 0.99-0.91 (m, 4H), 0.00 (s, 9H).To a solution of Step B product (0.3 g, 1.1 mmol) in DCM(10 ml) was added SOC12 (0.8 ml, 10.8 mmol) dropwise at 0C, then the reaction mixture was stirred at room temperature for 3 hours. When TLC showed that the reaction completed, the reaction mixture was diluted with DCM (50 mL), washed with sat. aq. NaHCO3 (50 mL) and brine (50 mL), dried over Na2SO4 and concentrated under reduced pressure to afford a mixture of 5-(chloromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)- 1 H-benzo[d] imidazole and 6-(chloromethyl)- 1 -((2- (trimethylsilyl) ethoxy)methyl)-1H-benzo[d]imidazole as an oil, which was used in next step without further purification. LC/MS (m/z): 297 (M+H).

According to the analysis of related databases, 26663-77-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MSD R&D (CHINA) CO., LTD.; CAI, Jiaqiang; CRESPO, Alejandro; DU, Xiaoxing; DUBOIS, Byron Gabriel; LIU, Ping; LIU, Rongqiang; QUAN, Weiguo; SINZ, Christopher; WANG, Liping; (61 pag.)WO2016/49100; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 39021-62-0, name is 1-Methyl-1H-imidazole-5-carbaldehyde, 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 39021-62-0, COA of Formula: C5H6N2O

A solution of isopropylmagnesium chloride/lithium chloride complex (1.3 M in THF, 10.6 mL, 13.8 mmol) was added dropwise by syringe to a solution of 4-bromo-2-(trifluoromethyl)pyridine (3.12 g, 13.8 mmol) in dry THF (50 mL) at 0 C. After 30 minutes, a solution of 1-methyl-1H-imidazole-5-carbaldehyde (1.38 g, 12.5 mmol) in THF (28.5 mL) was added to the Grignard solution by syringe at 0 C. The reaction mixture was warmed to room temperature over 2 hours after which it was quenched with saturated aqueous ammonium chloride solution. The mixture was partitioned between water and ethyl acetate. The separated aqueous phase was further extracted with ethyl acetate and washed with saturated aqueous NaCl solution. The organic phase was dried (MgSO4), filtered, and concentrated. The crude product was purified by flash column chromatography (silica gel, 0-10% MeOH-DCM) to provide the title compound.

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-imidazole-5-carbaldehyde, other downstream synthetic routes, hurry up and to see.

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

6160-65-2, name is 1,1′-Thiocarbonyldiimidazole, belongs to imidazoles-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. SDS of cas: 6160-65-2

INTERMEDIATE 45Methyl 3-(f(35r)-4-(aminocarbonothioyl)mophiholin-3-yllmethyl|-l-methyl-lH-indole-5- carboxylateTo a stirred slurry of Intermediate 44 (31.64 g, 109.7 mmol) in TetaF (221 mL) at r.t. was added l,r-thiocarbonyldiimidazole (21.51 g, 120.7 mmol) portionwise over 10 minutes. The reaction mixture was stirred at r.t. for 5 h, then transferred to a pressure vessel and NH3 (111 mL of a 28% aqueous solution, 1.6 mol) was added. This mixture was stirred at 600C for 17 h, then cooled to r.t. It was diluted with water (158 mL) and solid product was filtered off, washed with water and dried in vacuo at 450C, to give the title compound (37.79 g, 99.1%) as a white solid. LCMS (ES+) 348.0 (M+H)+, RT 2.88 minutes (Method I).

The synthetic route of 6160-65-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UCB PHARMA S.A.; WO2009/71895; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 939-70-8,Some common heterocyclic compound, 939-70-8, name is 1-(1H-Benzo[d]imidazol-2-yl)ethanone, molecular formula is C9H8N2O, 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.

General procedure: A 10%solution of NaOH (5 ml) in EtOH was added to a solutionof 2-acetylbenzimidazole (4) (1.6 g, 0.01 mol) in absoluteEtOH (20 ml) at 0C with stirring. Then the solution of anaromatic aldehyde (0.01 mol) in absolute EtOH (10 ml)was added dropwise. The reaction mixture was stirred for12 h at room temperature. After completion of reaction(monitored by TLC), the reaction mixture was poured ontocrushed ice. The separated solid was filtered off, washedwith water, and dried. The residue was purified by columnchromatography (silica gel, eluent 10% ethyl acetate inpetroleum ether) to afford pure benzimidazole-derived chalcone 5a-m.

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

Reference:
Article; Meshram, Gangadhar A.; Vala, Vipul A.; Chemistry of Heterocyclic Compounds; vol. 51; 1; (2015); p. 44 – 50; Khim. Geterotsikl. Soedin.; vol. 51; 1; (2015); p. 44 – 50,7;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 2302-25-2,Some common heterocyclic compound, 2302-25-2, name is 4-Bromo-1H-imidazole, molecular formula is C3H3BrN2, 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.

General procedure: A mixture of 4-methyl-3-(4-(pyridin-2-ylmethoxy)benzamido)phenyl boronic acid (50 mg, 0.14 mmol), Cs2CO3 (135 mg, 0.41 mmol), Pd(PPh3)4(23.93 mg, 0.02 mmol) and 4-bromo-1H-imidazole (26 mg, 0.18 mmol) was purged with nitrogen before adding degassed dioxane (690 muL) and water (230 muL) and heating in a microwave for 40 min at 150 C. After cooling, the aqueous layer was removed with a pipette, and the organic layer was diluted with DMSO (1 mL) and filtered through a 0.2 mum filter. The filtrate was concentrated to a volume of 1 mL and purified by Gilson HPLC (20-75% MeCN/10 mM NH4OAc in water). The fractions were concentrated and lyophilized to yield the product (19 mg, 0.049 mmol, 35%). 1H NMR (DMSO-d6) delta ppm 12.11 (s, 1H), 9.76 (s, 1H), 8.59 (d, 1H), 7.97 (d, 2H), 7.85 (td, 1H), 7.70 (s, 1H), 7.67 (s, 1H), 7.56 (m, 2H), 7.36 (dd, 1H), 7.21 (d, 1H), 7.15 (d, 2H), 5.27 (s, 2H), 2.18 (s, 3H). LCMS (M+H) = 385.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Bromo-1H-imidazole, its application will become more common.

Reference:
Review; Yang, Bin; Hird, Alexander W.; Russell, Daniel John; Fauber, Benjamin P.; Dakin, Les A.; Zheng, Xiaolan; Su, Qibin; Godin, Robert; Brassil, Patrick; Devereaux, Erik; Janetka, James W.; Bioorganic and Medicinal Chemistry Letters; vol. 22; 14; (2012); p. 4907 – 4911;,
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. 5465-29-2, name is 2-Propylbenzimidazole, A new synthetic method of this compound is introduced below., Application In Synthesis of 2-Propylbenzimidazole

Step A: 2-Propyl-1-(4-(2–t-butoxycarbonylbenzoyl)phenyl)methylbenzimidazole To a suspension of NaH (0.013 mg) in dry DMF (3 ml), 2-propyl benzimidazole (0.052 g, 0.325 mmol) was added, and the mixture was stirred at room temperature for 30 minutes to give a clear solution. To the solution was added t-butyl-2-[4–(bromomethyl)benzoyl]benzoate (0.125 g, 0.33 mmol) [prepared according to the procedure described in European Patent Application 0,253,310]. The mixture, after stirring at room temperature for 3 hours, was poured into ice-water (50 ml) and extracted with ethyl acetate (3 x 20 ml). The combined organic phase was washed with brine, then dried (MgSO4), and evaporated. The crude product was then purified by flash chromatography on silica-gel using ethyl acetate-hexane (1:6). Yield 0.12 g (81%, as amorphous solid). NMR(CDCl3): delta 1.0 (t, J=7Hz, 3H), 1.26 (s, 9H), 1.88 (m, 2H), 2.86 (t, J=7Hz, 2H), 5.4 (s, 2H), 7.05-7.8 (m, 12H); FAB-MS: m/e 455 (M+H).

The synthetic route of 5465-29-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Merck & Co., Inc.; EP400835; (1990); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

These common heterocyclic compound, 33543-78-1, name is Ethyl 1H-imidazole-2-carboxylate, 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. Safety of Ethyl 1H-imidazole-2-carboxylate

(Reference Example 8) Synthesis of ethyl 1-(difluoromethyl)-1H-imidazole-2-carboxylate: Potassium carbonate (1.28 g, 9.28 mmol) and sodium chlorodifluoroacetate (1.31 g, 8.56 mmol) were added to a solution of ethyl 1H-imidazole-2-carboxylate (1.00 g, 7.14 mmol) in acetonitrile (35 mL) at room temperature and the resultant mixture was stirred at 60°C for 24 hours. Further, potassium carbonate (0.640 g, 4.63 mmol) and sodium chlorodifluoroacetate (0.660 g, 4.33 mmol) were added at room temperature and the reaction liquid was stirred at 80°C for 8 hours. The reaction liquid was cooled to room temperature and distilled water was added to the reaction liquid and the reaction liquid was extracted with ethyl acetate. The organic layer was washed with a 10percent aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, hexane/ethyl acetate) to obtain ethyl 1-(difluoromethyl)-1H-imidazole-2-carboxylate (0.838 g, 4.41 mmol, 62percent) as a colorless oil. 1H-NMR (400 MHz, CDCl3) delta: 1.46 (3H, t, J=7.2 Hz), 4.47 (2H, q, J=7.2 Hz), 7.28 (1H, s), 7.53 (1H, d, J=1.6 Hz), 8.16 (1H, t, J=60.8 Hz).

The synthetic route of Ethyl 1H-imidazole-2-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Toray Industries, Inc.; ARAI Tadamasa; MORITA Yasuhiro; UDAGAWA Shuji; ISEKI Katsuhiko; IZUMIMOTO Naoki; (95 pag.)EP3263565; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 3314-30-5, 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. 3314-30-5 name is 1H-Benzo[d]imidazole-2-carbaldehyde, 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 methyl diethylphosphonoacetate(3.17g, 15.0 mmol) in dry THF (40 mL) was added sodium carbonate (3.79 g, 27.4 mmol), the mixturewas stirred for 30 min at room temperature prior to the addition of compound 2 (2.0 g, 13.7 mmol).The mixture was stirred and refluxed for 24 h under an argon atmosphere and monitored by TLC.After complete conversion of starting material, the reaction mixture was filtered, the filtrate wasconcentrated and re-dissolved by ethyl acetate, and then washed with saturated NaCl solution anddried over anhydrous sodium sulfate, concentrated in vacuo and purified by flash silica gel column(PE/EA = 4/1, v/v) to obtain 3 as white solid in 87.5% yield. LC-MS m/z: 203.1 [M + H]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1H-Benzo[d]imidazole-2-carbaldehyde, and friends who are interested can also refer to it.

Reference:
Article; Wang, Shuxiang; Guan, Lihong; Zang, Jie; Xing, Kun; Zhang, Jian; Liu, Dan; Zhao, Linxiang; Molecules; vol. 24; 7; (2019);,
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Imidazole | C3H4N2 – PubChem

Electric Literature of 20485-43-2, 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 20485-43-2 as follows.

Example 16 rac-(3aR,14bR)-10-Cyclohexyl-N7-(dimethylsulfamoyl)-13-methoxy-N3a,N3a- dimethyl-2-((l-methyl-lH-imidazol-2-yl)carbonyl)-l,2,3,14b-tetrahydroindolo[2,l- a]pyrrolo[3,4-d][2]benzazepine-3a, 7(4H)-dicarboxamide. HATU (37.5 mg, 0.099 mmol) was added to a solution of rac-(3aR,14bR)-10-cyclohexyl-N7- (dimethylsulfamoyl)-13-methoxy-N3a,N3a-dimethyl-l,2,3,14b-tetrahydroindolo[2,l- alpha]pyrrolo[3,4-d][2]benzazepine-3a,7(4H)-dicarboxamide (30 mg, 0.049 mmol) and 1- methyl-lH-imidazole-2-carboxyIic acid (12.5 mg, 0.099 mmol) in DMF (1 mL) and TEA (0.03 mL, 0.2 mmol). The reaction mixture was stirred at rt for 16 h, diluted with MeOH, and purified by preparative HPLC (H2O/MeOH with 0.1% TFA buffer) to yield rac-(3aR,14bR)-10-cyclohexyl-N7-(dimethylsulfamoyl)-13-methoxy-N3a,N3a- dimethyl-2-(( 1 -methyl-1H-imidazol-2-yl)carbonyl)- 1 ,2,3 , 14b-tetrahydroindolo[2, 1 – alpha]pyrrolo[3,4-d][23benzazepine-3a,7(4H)-dicarboxamide (20.3 mg, 0.028 mmol, 57% yield) as a bright yellow solid. Complex mixture of rotamers was observed, partial 1H NMR (aromatic region) reported for 2 major rotamers (~3:2 ratio). 1H NMR (500 MHz, DMSO-d6) delta 6.78 (s, 0.6H), 6.91 (s, 0.4H), 7.00 (s, 0.4H), 7.05 (s, 0.4H), 7.08 – 7.22 (m, 2.2H), 7.32 (d, J= 8.2 Hz, 0.6H), 7.37 (d, J= 8.2 Hz, 0.4H), 7.54 (dd, J= 8.6, 1.2 Hz, 0.4H), 7.61 (dd, J= 8.6, 1.2 Hz, 0.6H), 7.81 (d, J= 8.6 Hz, 0.6H), 7.84 (d, J= 8.6 Hz, 0.4H), 8.09 (br s, 0.4H), 8.31 (br s, 0.6H), 11.31 (s, 0.4H), 11.69 (s, 0.6H). LCMS: m/e 716 (M+H)+, ret time 3.67 min, 4 minute gradient.

According to the analysis of related databases, 20485-43-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; WO2009/120733; (2009); 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. 3034-38-6, name is 5-Nitro-1H-imidazole, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 5-Nitro-1H-imidazole

General Procedure:To a solution of 3-chloro-1-phenylpropan-1-one (2, 2.0 mmol) in toluene (25-30 mL) was added azoles (3.0 mmol) and triethylamine (4.0 mmol) at room temperature. The reaction mixture was heated at reflux under stirring for 3-4h in an oil bath. Solvent was distilled off under reduced pressure and the residue was taken into ethyl acetate (20 mL). Organic layer was washed with water (10 mL x 3) and dried over sodium sulfate. Sodium sulfate was filtered off and washed with ethyl acetate (5 mL x 2). The combined filtrate was concentrated under reduced pressure to yield crude product which was purified by recrystallization with ethyl acetate/hexane to give 3-(substituted 1H- azol-1-yl)-1-phenylpropan-1-one (3-9).

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 3034-38-6.

Reference:
Article; Kumar, Lalit; Sarswat, Amit; Lal, Nand; Jain, Ashish; Kumar, Sumit; Kiran Kumar; Maikhuri, Jagdamba P.; Pandey, Atindra K.; Shukla, Praveen K.; Gupta, Gopal; Sharma, Vishnu L.; Bioorganic and Medicinal Chemistry Letters; vol. 21; 1; (2011); p. 176 – 181;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem