Category: imidazoles-derivatives

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 150058-27-8 as follows. Safety of Methyl 2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

The 45g2-ethoxy -1H-benzimidazole-7-carboxylic acid and 500 ml by adding dichloromethane for added to a reaction flask, stirring cooling to 20 °C the following, to-drop 50.7g triethylamine, the drop finishes, drop by adding 54.0g to toluene sulfonyl chloride and 100 ml dichloromethane mixed solution, drop Bi Yu 10-20 °C stirring reaction 3h, for 10-20 °C adding 39.7g4-hydroxymethyl-5-methyl -1,3-dioxol-2-one, the temperature rising to adding 30-40 °C stirring reaction, with used in HPLC. After the reaction is complete, cooling to 15-25°C, by adding 400 ml purified water stirring, layered, with 30g drying by anhydrous sodium sulfate. Decompression jeung dry dichloromethane, by adding 300 ml methyl tert-butyl ether refined, cooling to 0-5 °C stirring crystallization 3h, filtering, with 20 ml cool to 0-5 °C methyl tert-butyl ether washing, for 40-50 °C reduced-pressure drying to the job (5-methyl-2-oxo -1,3-dioxol-4-yl) methyl 2-ethoxy -1H-benzo[d] imidazol-7-carboxylic acid ester 63.6 g. The yield of 91.6percent, purity 98.1percent

According to the analysis of related databases, 150058-27-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Long days Chongqing Pharmaceutical Co., Ltd; Meng, Wenxue; Long, Daobing; Chen, Shunxiang; (14 pag.)CN105622595; (2016); 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. 106429-59-8, name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde

Step 5.5-((7-(5-((5-fluoro-2′-(1-hydroxypropan-2-yl)-[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 (1143) (1144) To a suspension of 2-(2′-((4-(2,7-diazaspiro[4.4]nonan-2-yl)pyrimidin-5-yl)oxy)- 5′-fluoro-[1,1′-biphenyl]- 2-yl)propan-1-ol (20 mg, 0.45 mmol) and 2-oxo-2,3-dihydro- 1H-benzo[d]imidazole-5-carbaldehyde (Intermediate 40, 7.3 mg,0.045 mmol) in anhydrous MeOH (3 mL) was added NaBH3CN (5.8 mg, 0.09 mmol) under a nitrogen atmosphere and the mixture was stirred at 60-65 C for 16 h. An additional batch of 2- oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde (10 mg, 0.062 mmol) and NaBH3CN (7 mg, 0.11 mmol) were added, the reaction mixture was stirred at 60-65 C for an additional 18 h. The reaction mixture was concentrated under reduced pressure and purified by RP-HPLC-method A to give 5-((7-(5-((5-fluoro-2′-(1-hydroxypropan-2-yl)- [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: 13 mg. LCMS method E: Rt = 1.752 min, (M+H)+ = 595.2 1H NMR (CD3OD): delta 8.45 (s, 1H), 7.74 (s, 1H), 7.07- 7.44 (m, 10 H), 4.35-4.50 (m, 2H), 3.40-3.95 (m, 9H), 3.10-3.25 (m, 1H), 2.75-2.85 (m, 1H), 1.95-2.20 (m, 4H), 1.00-1.25 (m, 3H).19F NMR (C MeOD): delta -117.47, -76.69 ~ – 77.90.

According to the analysis of related databases, 106429-59-8, the application of this compound in the production field has become more and more popular.

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

Application of 89830-98-8, The chemical industry reduces the impact on the environment during synthesis 89830-98-8, name is 5-Cyclopropyl-1H-imidazole, I believe this compound will play a more active role in future production and life.

[0357] To a solution of Example 18a (1.00 g, 3.67 mmol) in DMF (10 mL) were added Cul (351 mg, 1.83 mmol), Cs2C03 (2.38 g, 7.30mmol), Example 18b(476 mg, 4.41 mmol), andN1,N2-dimethyl- cyclohexane-l,2-diamine (105 mg, 0.74 mmol). The resulting mixture was degassed with N2 and stirred at 130°C under microwave for 2 h. The mixture was diluted with MeOH and filtered. The filtrate was concentrated under vacuum and the residue was purified byPrep-HPLC (by Ultimate XB-C18, 50 x 250 mm, 10 mum, speed: 80 mL/min, eluent: H20/CH3CN = from 80/20 to 20/80 over 50 min)to give the desired product Example 18c (110 mg, yield 12percent) as a yellow solid. LC-MS: [M+H]+ = 253.0

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, 5-Cyclopropyl-1H-imidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; FRONTHERA U.S. PHARMACEUTICALS LLC; JIN, Bohan; DONG, Qing; HUNG, Gene; (227 pag.)WO2018/151830; (2018); 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 1003-21-0 as follows. SDS of cas: 1003-21-0

5-Bromo-1-methyl-1H-imidazole (6.66 g, 41.4 mmol) was added to a round bottom flask followed by tetrahydrofuran (150 mL) under an N2 atmosphere. The contents were cooled to 0 C. in an ice water bath. EtMgBr (3.0 M solution in THF, 13.3 mL, 39.8 mmol) was added slowly via syringe over approximately 5 minutes, then the ice bath was removed and the contents allowed to warm and stirred at room temperature for approximately 30 minutes. The vessel was then re-cooled to 0 C. and a solution of N-methoxy-N-methylpyrimidine-2-carboxamide (3.09 g, 15.9 mmol, Intermediate 66: step a) in THF (20 mL) was cannulated into the reaction vessel. The contents were allowed to stir at 0 C., then slowly warmed to room temperature, then heated to 40 C. in an oil bath for approximately 36 hours. The contents were then cooled to 0 C., quenched with a saturated aqueous NH4Cl solution, diluted with ethyl acetate and transferred to a separatory funnel. The aqueous layer was separated, extracted twice with EtOAc, then the combined organic phases were dried over MgSO4, filtered, then distilled under reduced pressure to yield an amber oil. The crude product was purified by flash column chromatography (silica gel, 0-10% DCM/(10% of a 2 M NH3 MeOH in DCM)) to provide the title compound.

According to the analysis of related databases, 1003-21-0, the application of this compound in the production field has become more and more popular.

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

Reference of 870837-18-6, A common heterocyclic compound, 870837-18-6, name is 3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde, molecular formula is C12H12N2O2, 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.

Synthesis of (Z)-(6S,9aR)-6-(3,4-difluorophenyl)-3-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]hexahydropyrido[2,1-c][1,4]oxazin-4-one A solution of (4R,6S)-6-(3,4-difluorophenyl)-3-hydroxyhexahydropyrido[2,1-c][1,4]oxazin-4-one (151 mg) and triphenylphosphonium bromide (220 mg) in acetonitrile (7 mL) was heated under reflux for one hour and then left to cool to room temperature. To the reaction solution, 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde (115 mg) and triethylamine (0.22 mL) were added, and the reaction solution was stirred at room temperature for 12 hours. Ethyl acetate and saturated sodium bicarbonate water were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with brine, dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane:ethyl acetate=1:1->ethyl acetate) to obtain 150 mg of the title compound. The property values of the compound are as follows. ESI-MS; m/z 466[M++H]. 1H-NMR(CDCl3) delta (ppm): 1.38-1.58(m,2H), 1.66-1.80(m,2H), 2.10-2.28(m,2H), 2.30(s,3H), 3.85(s,3H), 4.03(t,J=10.4 Hz,1H), 4.05-4.16(m,1H), 4.35(dd,J=10.4,2.0 Hz,1H), 5.33(t,J=4.0 Hz,1H), 6.82(s,1H), 6.92(brs,1H), 6.98-7.02(m,1H), 7.04-7.16(m,2H), 7.20(d,J=8.0 Hz,1H), 7.35(d,J=2.0 Hz,1H), 7.36(dd,J=8.0,2.0 Hz,1H), 7.71(d,J=1.2 Hz,1H).

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; Eisai R&D Management Co., Ltd.; US2007/117798; (2007); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

These common heterocyclic compound, 32673-41-9, name is 4-Imidazolemethanol hydrochloride, 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 4-Imidazolemethanol hydrochloride

C. By hydrolysis of the esters obtained by the Friedel-Crafts reaction. 2-hydroxy-3-[(1H-imidazol-4-yl)methyl]-benzoic acid and 2-hydroxy-5-[(1H-imidazol-4-yl)methyl]-benzoic acid (hydrochloride). 181 g (1.35 mole) of 1H-imidazole-4-methanol hydrochloride are added in portions to a mixture of 156 ml (1.2 mole) of methyl 2-hydroxybenzoate and 675 g of polyphosphoric acid heated to 80 C. The reaction mixture is maintained with good stirring at this temperature for 288 hours. The mixture is then decomposed on ice, and extracted twice with toluene. The aqueous phase is alkalinized to pH 9.5 by the addition of 790 ml of a saturated aqueous solution of sodium hydroxide. The mineral salts which precipitate are removed by filtration and washed with methanol. The methanolic washing solution is added to the aqueous phase and the resulting mixture is concentrated with partial elimination of the methanol. The solution is then alkalinized to pH 10.3 by addition of a 10N aqueous solution of sodium hydroxide, and is heated at 100 C. for one hour and a half so as to saponify the esters. The aqueous solution is neutralized to pH 7.5 by addition of 10 N hydrochloric acid, filtered on Norit (activated carbon) and the filtrate is evaporated under reduced pressure. The residue is taken up three times in succession in a toluene-ethanol mixture and dried by azeotropic distillation. It is then partially dissolved in hot methanol and the insoluble mineral salts are removed by filtration. The filtrate is evaporated under reduced pressure, the residue is redissolved in a minimum of water, and purification is then carried out by passing through a column of Amberlite IR93 (height of the column: 60 cm; diameter: 8 cm; equivalence: 2.64 mole). Excess 1H-imidazole-4-methanol, together with its polymers, are eluted with water (the pH of the elude varies from 11.2 to 7.3). The elution is then continued with a 4% aqueous solution of hydrochloric acid. The acid elude (9 liters) is adjusted to pH 7.7 by addition of a saturated agueous solution of sodium hydroxide and is then evaporated under reduced pressure. The residue thus obtained is once again dried by azeotropic distillation with a toluene-ethanol mixture, and is then taken up in 1.6 liter of acetonitrile. It is then filtered. The residue on the filter (129 g) is chromatographed on silica (800 g, 15 mum) after having been previously deposited on 300 g of silica (0.2 to 0.5 mm) (eluent: 75:25 v/v ethyl acetate-ethanol). 5.99 g of 2-hydroxy-3-[(1H-imidazol-4-yl)methyl]-benzoic acid is thus obtained. M.P.: 245-252 C. (water). At the same time, 31 g of 2-hydroxy-5-[(1H-imidazol-4-yl)methyl]-benzoic acid are obtained.

The synthetic route of 4-Imidazolemethanol hydrochloride has been constantly updated, and we look forward to future research findings.

Reference:
Patent; U C B Societe Anonyme; US4923865; (1990); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 288-32-4, 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. 288-32-4, name is 1H-Imidazole belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 1 N-(Triphenylmethyl)imidazole (2) A stirred suspension of triphenylmethanol (2.6 g, 10 mmol) and 1.36 g (20 mmol) of imidazole in 10 mL of HOAc was heated to 100° C. under N2 for 1 h. The cooled mixture was diluted with Et2 O and washed with water, saturated Na2 CO3, water (until neutral), brine, dried (MgSO4), filtered and concentrated. The crude product was purified by flash chromatography (110 g SiO2, 25percent-50percent EtOAc-hexanes) to give 0.78 g (25percent) of a solid. This was recrystallized from EtOAc to give 0.20 g of (2), m.p. 221°-223° C. IR (KBr) 1489, 1443, 1210, 1072, 750, 701, 662 cm-1. NMR (CDCl3): d 6.82, 7.07, 7.47 (all t, J=1, imidazole CH); 7.14 (m, 6H); 7.32 (m, 9H). Anal. Calc’d (C22 H18 N2): C, 85.13; H, 5.84; N, 9.03. Found: 85.16; 5.87; 9.02.

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

Reference:
Patent; Alcon Laboratories, Inc.; US6051573; (2000); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

496-46-8, name is Tetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-dione, 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. HPLC of Formula: C4H6N4O2

Synthesis of cucurbit[n]urils in hydrochloric acid using paraformaldehyde Unsubstituted glycoluril (20 g) and hydrochloric acid (37 % w/v, 30 mL) were placed in a reaction flask and heated to 90C. Paraformaldehyde (8.87 g) was added in portion-wise and the reaction mixture was then heated to 100 C (internal) for 18 hours. The reaction mixture was cooled and added to methanol (150 mL) to produce a beige powder which was analysed by1H NMR.Approximate Yields by1H NMR (% of recovered product) cucurbit[5]uril 8%, cucurbit[6]uril 44%, cucurbit[7]uril 28%, cucurbit[8]uril 18%, cucurbit[9]uril 0%, cucurbit[10]uril 0% cucurbit[11]uril 0%.Residual formaldehyde by HPLC method was 682 ppm.

The synthetic route of 496-46-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AQDOT LIMITED; COULSTON, Roger; DIEC, David; NOGUEIRA, Guilherme; GERARDUS DE ROOIJ, Johannes; (23 pag.)WO2018/115822; (2018); 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. 930-62-1, name is 2,4-Dimethylimidazole, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 930-62-1

PREPARATIVE EXAMPLE 51. A mixture of 2-chloroethylamine hydrochloride (7.66 g, 66 mmol), 2,4- dimethylimidazole (5.88 g, 61 mmol), tetrabutyl ammonium sulfate (0.83 g, 2.5 mmol), solid NaOH (8.81 g, 220 mmol) and anhydrous acetonitrile (80 mL) Is stirred at reflux for 48 h under N2- The mixture is filtered, concentrated in vacuo and purified by flash column chromatography (silica gel) using 2% MeOH-CH2Cl2 saturated with aqueous ammonium hydroxide to give the title compound.

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 930-62-1.

Reference:
Patent; SCHERING CORPORATION; WO2007/84498; (2007); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 4238-71-5, 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. 4238-71-5 name is 1-Benzyl-1H-imidazole, 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: To a mixture of acetylene 2 (127 mg, 1 mmol) and S (32 mg, 1 mmol) was added 1-methylimidazole (1a; 82 mg, 1 mmol). The mixture was stirred at 20-25 C for 24 h. Column chromatography afforded thione 3a (132 mg, 67%), 4.3.7 (Z)-3-(3-Benzyl-2-thioxo-2,3-dihydro-1H-imidazol-1-yl)-3-phenyl-2-propenenitrile (3e) Analogously, from acetylene 2 (64.0 mg, 0.5 mmol), S (16.0 mg, 0.5 mmol), and 1-benzylimidazole (1e; 79.0 mg, 0.5 mmol) in MeCN (1 mL) (20-25 C, 24 h) thione 3e (27 mg, 96%) was obtained as a light-yellow microcrystalline powder, mp 129-131 C (washed with ether). Initial imidazole 1e was recovered (65 mg, conversion was 18%). 1H NMR (400.13 MHz, CDCl3): delta=7.50-7.30 [m, 10H, Ho,m,p from C(6)-Ph and Ph from N-Bn], 6.74 (s, 2H, 4-H, 5-H), 6.06 (s, 1H, 7-H), 5.27 (s, 2H, CH2 from N-Bn) ppm. 13C NMR (100.62 MHz, CDCl3): delta=164.7 (C-2), 154.1 (C-6), 135.2 (Ci, Ph from N-Bn), 132.4 [Ci from C(6)-Ph], 131.8 [Cp from C(6)-Ph], 129.1 [Cm from C(6)-Ph], 128.9 (Cm, Ph from N-Bn), 128.2 (Cp, Ph from N-Bn), 128.1 (Co, Ph from N-Bn), 126.7 [Co from C(6)-Ph], 118.3 (C-4), 117.1 (C-5), 114.5 (CN), 97.2 (C-7), 51.3 (CH2 from N-Bn) ppm. IR (KBr): 2221 (CN), 1621 (C=C), 1398 (C=S) cm-1. Anal. Calcd for C19H15N3S (317.41): C, 71.90; H, 4.76; N, 13.24; S, 10.10. Found: C, 71.67; H, 4.85; N, 12.92; S, 9.84.

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

Reference:
Article; Belyaeva, Kseniya V.; Andriyankova, Ludmila V.; Nikitina, Lina P.; Mal’Kina, Anastasiya G.; Afonin, Andrei V.; Ushakov, Igor A.; Bagryanskaya, Irina Yu.; Trofimov, Boris A.; Tetrahedron; vol. 70; 5; (2014); p. 1091 – 1098;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem