Month: February 2021

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;,
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 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

Adding a certain compound to certain chemical reactions, such as: 6160-65-2, name is 1,1′-Thiocarbonyldiimidazole, 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 6160-65-2, Product Details of 6160-65-2

A solution of the amine (0.1 10 g, 0.43 mmol) in anhydrous CH2CI2 (2 mL) was added dropwise over 2-5 minutes to an ice-salt bath cooled solution of 1 , 1 ‘-thiocarbonyldiimidazole (95%, 0.162 g, 0.87 mmol, 2 eq.) in anhydrous CH2CI2 (6 mL). After 15 minutes, the cooling bath was removed and the reaction mixture was stirred at room temperature for 1 .5 hours after which time analysis by TLC (10% MeOH in CH2CI2) indicated complete consumption of the starting aniline. The mixture was cooled once again in an ice bath and 7 M NH3 in MeOH (620 muIota_, 4.3 mmol, 10 eq.) was added dropwise over 2-5 minutes. The bath was removed and the mixture was stirred over night at room temperature. Silica gel (~1 g) was added and the mixture was concentrated to dryness under reduce pressure. Flash column chromatography (RediSepRf Si02 (40 g), 100% CH2CI2? 10% MeOH in CH2CI2) gave the thiourea as an amber oil that solidified upon standing (0.130 g, 97%).

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

Reference:
Patent; DUKE UNIVERSITY; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; LIEDTKE, Wolfgang; STEINHOFF, Martin; GUILAK, Farshid; (150 pag.)WO2016/28325; (2016); 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. 17325-26-7, name is Methyl 1H-imidazole-5-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C5H6N2O2

A solution of [1H-IMIDAZOLE-4-CARBOXYLIC] acid methyl ester (1.0 g, 7.93 mmol) in [N, N] dimethylformamide at [25 oC] was treated with triethylamine (2.2 mL, 15.86 mmol) and triphenylmethylchloride (2.43 g, 8.72 [MMOL).] The reaction was stirred at [25 oC] for 8 h and then concentrated in vacuo. The residue was diluted with ethyl acetate and then washed with water, a IN aqueous hydrochloric acid solution, water, and a saturated aqueous sodium chloride solution. The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60,230- 400 mesh, 50: 50 ethyl acetate/petroleum ether) afforded 1-trityl-1H-imidazole-4- carboxylic acid methyl ester (2. [88] g, 98.6%) as a white foam

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 17325-26-7.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2003/106459; (2003); A1;,
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 29043-48-9 as follows. SDS of cas: 29043-48-9

To a stirred solution of 2-methyl-1 H-benzo[d]imidazol-5-amine (187 mg) in DCM (5 mL) at 0 C was added 3-carbamoyl-4-hydroxybenzene-1 -sulfonyl chloride (lnt-1 , 300 mg). The reaction mixture was allowed to warm to RT and stirred for 16 hr. The reaction mixture was diluted with water (30 mL) and extracted with DCM (2 x 50 mL). The combined DCM extracts were washed with saturated brine (25 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to afford the crude product (300 mg). The crude product was purified by reversed phase preparative HPLC (Sunfire C18, 30 x 250 mm) using a gradient of 10-100% acetonitrile in 10 mM ammonium bicarbonate (aq). The desired fraction was concentrated under reduced pressure and the resulting solid was collected by filtration, washed with water (10 mL) and dried under vacuum to afford the titled compound (55.6. mg). LCMS m/z 347.04 (M+H)+. NMR after D20 exchange (400 MHz, DMSO-c/6) delta ppm 2.27 – 2.50 (m, 3 H) 6.76 (d, J=8.33 Hz, 1 H) 6.85 (dd, J=8.55, 1 .75 Hz, 1 H) 7.02 – 7.21 (m, 1 H) 7.28 (d, J=8.33 Hz, 1 H) 7.40 – 7.61 (m, 1 H) 8.19 (d, J=2.19 Hz, 1 H).

According to the analysis of related databases, 29043-48-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; ADAMS, Jerry Leroy; DUFFY, Kevin J.; GRAYBILL, Todd L.; MOORE, Michael Lee; NEIPP, Christopher E.; RALPH, Jeffrey M.; SQUIRE, Michael Damien; (304 pag.)WO2017/153952; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem