Imidazoles-derivatives

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. 5805-52-7, name is 1H-Benzimidazole-2-carboxamide, A new synthetic method of this compound is introduced below., Computed Properties of C8H7N3O

At room temperature, 3.0 g (18.6 mmol)1H-benzimidazole-2-carboxamide and 7.5 g (18.6 mmol)Lawson reagent placed in 250mL eggplant bottle,Add 150 mL of tetrahydrofuran to reflux at 66 C for 5 h.After the completion of the reaction, the solvent was evaporated to drynessWith methylene chloride dissolved, saturated sodium bicarbonate wash, saturated sodium chloride wash, the organic phase, anhydrous sodium sulfate drying, filtration, columnChromatography to obtain a white solid. Yield: 60.0%.

The synthetic route of 5805-52-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shenyang Pharmaceutical University; Zhao Linxiang; Liu Dan; Li Kun; Wang Shuxiang; Jing Yongkui; (21 pag.)CN106905241; (2017); A;,
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Imidazole | C3H4N2 – PubChem

Reference of 17325-26-7, 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. 17325-26-7, name is Methyl 1H-imidazole-5-carboxylate belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Intermediate 121 -(4-Cyano-2-fluoro-rhenyl)-1 H-imidazole-4-carboxylic acid methyl ester: A mixture of 3,4-difluorobenzonitrile (193 mg), 1 H-imidazole-4-carboxylic acid methylester (160 mg), and potassium carbonate (150 mg) in N-methyl-2-pyrrolidinone (4mL) is heated to 15000 for 30 mm in a microwave oven. After cooling to room temperature, the reaction mixture is diluted with water and ethyl acetate. The aqueous phase is extracted with ethyl acetate and the combined extracts are dried over MgSO4 and concentrated in vacuo. The residue is triturated with t-butyl methylether, filtered off, and dried to give the title compound. LC (method 4): tR = 0.78 mm; Mass spectrum (ESI): mlz = 246 [M+H]

The synthetic route of Methyl 1H-imidazole-5-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; NEUROCRINE BIOSCIENCES, INC.; NOSSE, Bernd; ECKHARDT, Matthias; HIMMELSBACH, Frank; LANGKOPF, Elke; ASHWEEK, Neil J.; HARRIOTT, Nicole; WO2014/19967; (2014); A1;,
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Imidazole | C3H4N2 – PubChem

Reference of 6154-30-9,Some common heterocyclic compound, 6154-30-9, name is 2,5-Dibromo-4-nitro-1H-imidazole, molecular formula is C3HBr2N3O2, 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.

A mixture consisting of 2, 5-dibromo-4- nitroimidazole (27.1 g, 100 mmol) and concentrated hydrochloric acid (434 ml) was stirred under heating (77C to 80C, 16 hours). The reaction mixture was left to cool, and then stirred under cooling on ice (5C to 10C, 2 hours). Thereafter, the precipitated crystals were collected by filtration and air-dried (50C, 5 hours). The yield of the dried product was 8.26 g. The filtrate was further extracted with ethyl acetate (300 ml) and then dried (MgSO4), followed by vacuum concentration and exsiccation. The yield of the exsiccated product was 9.63 g. Thus, 17.9 g (in total) of 2, 5-dichloro-4-nitroimidazole was obtained (yield: 98. 3%). IR (KBr) : 1566,1475, 1403,1366, 1332,1272, 1190, 1091,996, 834,679 cm-l. MS (70 eV) m/z (relative intensity): 183 (15, M+), 181 (25), 108 (28), 74 (42), 62 (100).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2,5-Dibromo-4-nitro-1H-imidazole, its application will become more common.

Reference:
Patent; OTSUKA PHARMACEUTICAL CO., LTD.; WO2005/77913; (2005); A1;,
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Imidazole | C3H4N2 – PubChem

Application of 570-22-9,Some common heterocyclic compound, 570-22-9, name is 1H-Imidazole-4,5-dicarboxylic acid, molecular formula is C5H4N2O4, 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 29 Diethyl imidazole-4,5-dicarboxylate (46) Imidazole-4,5-dicarboxylic acid (7.55 g, 50.0 mmol) is dissolved in absolute ethyl alcohol (120 mL). The solution was cooled in an ice bath to 0 C. and bubbled dry HCl gas for 1 h. Later, the reaction mixture was refluxed at 80 C. for 7 h during which time all the starting material was consumed. The solvent was removed and the residue that obtained was dissolved in dichloromethane (200 mL) and the organic layer was neutralized with triethylamine. The organic layer was washed with cold water (100 mL) and brine (50 mL), dried over anhydrous sodium sulfate and concentrated in vacuo to give 5.50 g (52%) of white solid: mp 175-177 C.; 1 H NMR (CDCl3) delta 1.40 (t, 3H), 4.41 (m, 2H), 7.84 (1H, C2 H) and 11.55 (br s, 1H, NH).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1H-Imidazole-4,5-dicarboxylic acid, its application will become more common.

Reference:
Patent; ICN Pharmaceuticals, Inc.; US6130326; (2000); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 641571-11-1, name is 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline, molecular formula is C11H10F3N3, 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. Product Details of 641571-11-1

A solution of 3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline(524 mg, 2.0 mmol) and Et3N (10 mmol) in anhydrous THF (6 mL) wascooled to 0 C in an ice bath. The light yellow solution preparedbefore was then added dropwise. The mixture was allowed to warm toroom temperatureand maintained for 1 h. The reaction mixture was quenched by addition of saturatedNaCl solution and the reaction mixture was extracted several times with EtOAc.Thecombined organic extracts were dried with Na2SO4,filtered, and concentrated in vacuo. The resultant crudematerial was purifiedby column chromatography to give the title compound 7 (873 mg, yield 90% of two steps). 1H NMR (400 MHz, DMSO-d6) d 10.80 (s, 1H), 8.66 (s, 1H),8.47 (d, J = 1.6 Hz, 1H), 8.39 (s, 1H), 8.19 (s, 1H), 7.98 (dd, J = 1.6, 8.0Hz, 1H), 7.79 (s, 1H), 7.66 (s, 1H), 7.53 (d, J = 8.0 Hz ,1H), 2.46 (s, 3H),2.24 (s, 3H). LC-MS (ESI):m/z 486 [M + H]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 641571-11-1, its application will become more common.

Reference:
Article; Lu, Xiaoyun; Zhang, Zhang; Ren, Xiaomei; Pan, Xiaofeng; Wang, Deping; Zhuang, Xiaoxi; Luo, Jingfeng; Yu, Rongmin; Ding, Ke; Bioorganic and Medicinal Chemistry Letters; vol. 25; 17; (2015); p. 3458 – 3463;,
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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 75370-65-9 as follows. Application In Synthesis of 4-Amino-1H-benzo[d]imidazol-2(3H)-one

Preparation of 1-(4-(trifluoromethyl)-2-morpholinobenzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea Amine 2d (300 mg, 1.15mmol) was dissolved in 20 ml of AcOEt and at 0C triphosgene (350 mg, 1 equiv.) was added to the solution. The mixture was warmed at 80C for 4 hours then evaporated and the residue was dissolved in 5ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1a (200 mg, 1.3 mmol) and the mixture was warmed at 80C for 8 hours. (TLC AcOEt 9.5 / MeOH 0.5). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1 X 20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 100mg of a pale yellow solid. Yield = 20% 1HNMR (DMSO, 200 MHz) delta 2.91 (4H, m), 3.76 (4H, m), 4.44 (2H, d, J = 5.6 Hz), 6.63 (1H, d, J = 7.6 Hz), 6.88 (3H, m), 7.64 (1H, d, J = 8.2 Hz), 7.73 (1H, d), 7.85 (1H, bs), 8.44 (1H, bs), 9.99 (1H, bs), 10.60 (1H, bs); [M+1] 436.2 (C20H20F3N5O3 requires 435.4).

According to the analysis of related databases, 75370-65-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Pharmeste S.r.l.; EP2377850; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

These common heterocyclic compound, 4887-88-1, name is 5-Bromo-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. Quality Control of 5-Bromo-1H-benzo[d]imidazole

General procedure: N-(Azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide TFA salt: 3-Amino-azetidine-1-carboxylic acid tert-butyl ester (1.2 g, 6.97 mmol) and (3-trifluoromethyl-benzoylamino)-acetic acid (1.57 g, 6.36 mmol) were treated with EDCI (1.57 g, 6.36 mmol), HOBT (1.22 g, 6.36 mmol) in DCM (10 mL) at room temperature for 4 hours. The reaction solution was partitioned between DCM and water. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give yellow oil, which was then purified by silica gel column on a CombiFlash system using hexanes and ethyl acetate (from 10% ethyl acetate to 100% ethyl acetate) to afford 3-[2-(3-trifluoro-methyl-benzoylamino)-acetylamino]-azetidine-1-carboxylic acid tert-butyl ester as white solid, 2.23 g, 80% yield. 1H NMR (400 MHz, CDCl3) d 8.10 (s, 1H), 8.02 (d, J = 6.6 Hz, 1H), 7.80 (d, J = 6.8 Hz, 1H), 7.56 (t, J = 6.5 Hz, 1H), 4.61 (m, 1H), 4.25 (t, J = 7.2 Hz, 2H), 4.18 (d, J = 5.5 Hz, 2H), 3.82 (t, J = 7.5 Hz, 2H), 1.41 (s, 9H). 3-[2-(3-Trifluoromethyl-benzoylamino)-acetylamino]-azetidine-1-carboxylic acid tert-butyl ester (2.10 g, 5.24 mmol) was dissolved in 1:1 TFA and DCM mixed solution (10 mL) at room temperature. The reaction was stirred for another 2 hours. The solvent was removed and the residue was dried to give N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide as a TFA salt containing extra TFA (colorless oil), ~ 2.5 g, 100% yield. 1H NMR (400 MHz, CDCl3) d 8.10 (s, 1H), 8.05 (d, J = 6.0 Hz, 1H), 7.78 (d, J = 6.2 Hz, 1H), 7.55 (m, 2H), 4.78 (m, 1H), 4.15 (d, J = 3.2 Hz, 2H), 3.95 (t, J = 7.0 Hz, 2H), 3.52 (t, J = 7.0 Hz, 2H).8-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,4-dioxa-spiro[4.5]dec-7-ene (PCT Int. Appl. WO2006064189, 0.292 g, 1.10 mmol), 5-bromobenzo[d][1,3]dioxole (Aldrich, 161 mg, 0.801 mmol), and tetrakis (triphenylphosphino)palladium(0) (Aldrich, 0.048 g, 0.042 mmol) were dissolved in 1,4-dioxane (9 mL), treated with 2M aqueous Na2CO3 (2.0 mL, 4.0 mmol), bubbled with argon for a few minutes, and heated to 100oC under reflux condenser for 24 h. After cooling to ambient temperature, the reaction was diluted with water (30 mL), extracted thrice with dichloromethane, aqueous layer acidified to ca. pH 7, extracted twice more with dichloromethane, and the combined organic layers washed with brine, dried over Na2SO4, filtered, and the filtrate concentrated in vacuo to give an orange oil. This was purified by thin layer chromatography on silica gel (EtOAc) to give 5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)benzo[d][1,3]dioxole as a yellow solid (110 mg, 53%). 5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)benzo[d][1,3]dioxole (110 mg, 0.42 mmol) in MeOH (5 mL) was placed in a hydrogenation Par Shaker under 40 psi at room temperature using 5% Pd/C (~ 50 mg) as catalyst for 2 hour. The resulting solution was filtered through a pad of Celite , concentrated and purified by silica gel column on a CombiFlash system to afford 5-(1,4-dioxaspiro[4.5]decan-8-yl)benzo[d][1,3]dioxole as white solid, 91 mg, 82% yield. 5-(1,4-dioxaspiro[4.5]decan-8-yl)benzo[d][1,3]dioxole (91 mg, 0.35 mmol) was treated with 1N HCl ( ~ 2 mL) in acetone (4 mL) at room temperature for 4 hours. The reaction was neutralized with saturate NaHCO3 solution and the solvent was removed. The residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give yellow solid, which was then purified by silica gel column on a CombiFlash system using hexanes and ethyl acetate (from 10% ethyl acetate to 100% ethyl acetate) to afford 4-(benzo[d][1,3]dioxol-5-yl)cyclohexanone as white solid, 75 mg, 98% yield.4-(benzo[d][1,3]dioxol-5-yl)cyclohexanone (75 mg, 0.35 mmol) and N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide TFA salt (151 mg, 0.50 mmol) in DCM (2 mL) was treated with TEA (0.1 mL, 0.75 mmol) for 10 min followed by NaBH(OAc)3 (Aldrich, 225 mg, 1.05 mmol) for another 4 hours at room temperature. The reaction was quenched with saturated sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted 3 times with chloroform and IPA “cocktail” (~ 3:1, v/v). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was then purified by a CombiFlash system using ethyl acetate and 7N NH3 in MeOH as eluent (from pure ethyl acetate to 5% 7N NH3 in MeOH in ethyl acetate) to afford two title compounds as white solids: 8a, less polar isomer (cis), 67 mg, 38% yield; 9a, more polar isomer (trans), 45 mg, 26% yield.

The synthetic route of 5-Bromo-1H-benzo[d]imidazole has been constantly updated, and we look forward to future research findings.

Reference:
Article; Zhang, Xuqing; Hufnagel, Heather; Markotan, Thomas; Lanter, James; Cai, Chaozhong; Hou, Cuifen; Singer, Monica; Opas, Evan; McKenney, Sandra; Crysler, Carl; Johnson, Dana; Sui, Zhihua; Bioorganic and Medicinal Chemistry Letters; vol. 21; 18; (2011); p. 5577 – 5582;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 106429-59-8, 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. 106429-59-8 name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-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.

Step 4.5-((7-(5-((5-fluoro-2′-(1-hydroxyethyl)-[1,1′-biphenyl]-2-yl)oxy)pyrimidin-4-yl)- 2,7-diazaspiro[4.4]nonan-2-yl)methyl)-1H-benzo[d]imidazol-2(3H)-one (1074) To a solution of 1-(2′-((4-(2,7-diazaspiro[4.4]nonan-2-yl)pyrimidin-5-yl)oxy)-5′- fluoro-[1,1′-biphenyl]-2-yl)ethanol (330 mg, 0.66 mmol, crude) and 2-oxo-2,3-dihydro- 1H-benzo[d]imidazole-5-carbaldehyde (Intermediate 40, 106 mg, 0.66 mmol,) in MeOH (10 mL, anhydrous) was added AcOH (0.2 mL). The mixture was stirred at 17-25 C for about 30 min, then NaBH3CN (82 mg, 1.32 mmol) was added and the resulting mixture was stirred at 17-25 C for about 16 h. The mixture was quenched by sat. aq. NaHCO3 (10 mL) and extracted with CH2Cl2 (3 ¡Á 20 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated to give a residuewhich was purified by RP-HPLC method A to give 5-((7-(5-((5-fluoro-2′-(1- hydroxyethyl)-[1,1′-biphenyl]-2-yl)oxy)pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2- yl)methyl)-1H-benzo[d]imidazol-2(3H)-one (TFA salt) as a white solid. Yield: 290 mg. LCMS method C: Rt = 0.593 min, (M+H)+ = 581.21H NMR (CD3OD): delta 8.00-8.15 (m, 1 H), 7.50-7.70 (m, 2 H), 6.90-7.40 (m, 9 H), 4.67 (s, 1 H), 4.43 (s, 2 H), 3.35-3.95 (m, 8 H), 1.90-2.25 (m, 4 H), 1.20-1.35 (m, 3 H).19F NMR (CD3OD): delta -76.92, -117.29 ~ – 118.17.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, and friends who are interested can also refer to it.

Reference:
Patent; VITAE PHARMACEUTICALS, INC.; CACATIAN, Salvacion; CLAREMON, David, A.; DILLARD, Lawrence, Wayne; DONG, Chengguo; FAN, Yi; JIA, Lanqi; LOTESTA, Stephen, D.; MARCUS, Andrew; MORALES-RAMOS, Angel; SINGH, Suresh, B.; VENKATRAMAN, Shankar; YUAN, Jing; ZHENG, Yajun; ZHUANG, Linghang; PARENT, Stephan, D.; HOUSTON, Travis, L.; (444 pag.)WO2017/214367; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 5465-29-2, 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 5465-29-2 as follows.

Step 3) Methyl 2-[4-[(2-Propyl-1H-benzimidazol-1-yl)methyl]phenyl]-3-pyridinecarboxylate To a solution of 2-propyl-1H-benzimidazole (67 mg, 0.42 mmol) in DMF (1.5 mL) was added NaH (60% dispersion in mineral oil; 17 mg, 0.42 mmol). After 20 min, a solution of methyl 2-[(4-chloromethyl)phenyl]-3-pyridinecarboxylate (100 mg, 0.38 mmol) in DMF (3 mL) was added. After 20 h, the mixture was cooled (0 C.) and water (10 mL) and brine (5 mL) were added. The mixture was extracted with EtOAc, and the combined extracts were washed with brine, dried, and concentrated. Purification by flash chromatography (30% EtOAc/hexane) gave 138 mg (94%) of product as a colorless oil. 1 H NMR (CDCl3) delta 0.96 (t, J=7.3 Hz, 3H), 1.81 (m, 2H), 2.77 (t, J=7.9 Hz, 2H), 3.61 (s, 3H), 5.32 (s, 2H), 7.05 (d, J=8.3 Hz, 2H), 7.14 (m, 3H), 7.26 (dd, J=7.8, 4.8 Hz, 1H), 7.42 (d, J=8.3 Hz, 2H), 7.71 (d, J=7.6 Hz, 1H), 8.03 (dd, J=7.8, 1.8 Hz, 1H), 8.68 (dd, J=4.8, 1.8 Hz, 1H).

According to the analysis of related databases, 5465-29-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; American Home Products Corporation; US5283242; (1994); A;,
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. 3314-30-5, name is 1H-Benzo[d]imidazole-2-carbaldehyde, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 3314-30-5

General procedure: The equimolar aldehyde 3a?3d (1 mmol) and substituted phenylhydrazine 5a?5s (1 mmol) weremixed in CH3OH (10 mL) and stirred at room temperature [18]. After about 2 h, the reaction wascompleted (monitored by TLC). The residual crude was purified via silica gel column chromatogramusing a gradient mixture of petroleum ether and ethyl acetate to obtain the pure target compounds6a?6ai (in 45?80percent yield).

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 3314-30-5.

Reference:
Article; Wang, Xing; Chen, Yong-Fei; Yan, Wei; Cao, Ling-Ling; Ye, Yong-Hao; Molecules; vol. 21; 11; (2016);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem