Author: Jessica.F

Synthetic Route of 53484-17-6,Some common heterocyclic compound, 53484-17-6, name is 1-Methyl-1H-benzo[d]imidazole-5-carboxylic acid, molecular formula is C9H8N2O2, 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.

(4aR,9aS)-2,3,4,4a,9,9a-hexahydro-1Hindeno[2,1-b]pyridine-6-carbonitrile (0.91 g, 4.59 mmol) and 1-methyl-1Hbenzimidazole-5-carboxylic acid (1.02 g, 95.0%, 5.51 mmol, 1.2 Eq) were addedinto a 100-ml round-bottom flask. Anhydrous acetonitrile (5 ml) was added, andstirring was started to obtain a slurry. Triethylamine (2.56 ml, 18.38 mmol, 4.0Eq) was added at room temperature. The reaction mixture was cooled toapproximately 3C and propane phosphonic acid anhydride [3.05 g, 50 wt.% intetrahydrofuran (THF), 4.80 mmol, 1.05 Eq] was added dropwise, keeping theinternal temperature below 11C. The resulting slurry was stirred at roomtemperature and monitored by HPLC and LC-MS for conversion. After 20 hoursat room temperature, the reaction reached approximately 98% conversion. Water(5 ml) was added dropwise, keeping the internal temperature below 35C.Subsequently, a 50% sodium hydroxide aqueous solution (1.84 g, 22.97 mmol,5.0 Eq) was added. The resulting mixture was stirred at room temperature for2 hours. The mixture was extracted with 2-methyl-THF (2 50 ml), and thelayers were separated. The combined organic layers were dried over anhydrousmagnesium sulfate (MgSO4), filtered and concentrated to give a crude oil, which was purified by flash chromatography (100 g silica gel 230-400 mesh) by elutionwith pure ethyl acetate first, and then a solution of 5%-20% methanol in ethylacetate. The fractions containing the desired product were pooled togetherand concentrated under vacuum to give (4aR,9aS)-1-(1-methyl-1H-benzo[d]-imidazole-5-carbonyl)-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridine-6-carbonitrile (N-methylbenzimidazole regioisomer 1, M1) as an off-white solid(1.50 g, 91.6% yield). The identity of M1 was confirmed by NMR analysis (1H,13C, correlation spectroscopy, rotating-frame nuclear Overhauser effect correlationspectroscopy, heteronuclear multiple quantum coherence, and heteronuclearmultiple bond coherence) in DMSO-d6 at 80C (Supplemental Figs. 1-6). 1HNMR (CD3SOCD3, 600 MHz, 353 K) d 8.18 (s, 1H), 7.67 (d, J = 1.2 Hz, 1H),7.63 (s, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.55 (dd, J = 7.8 and 1.8 Hz, 1H), 7.41 (d, J= 7.8 Hz, 1H), 7.32 (dd, J = 7.8 and 1.8 Hz, 1H), 4.80 (br, 1H), 4.05 (br, 1H), 3.84(s, 3H), 3.24 (dd, J = 16.2 and 10.8 Hz, 1H), 3.14 (dt, J = 11.4 and 6.6 Hz, 1H),2.95-3.05 (m, 2H), 1.98-2.04 (m, 1H), 1.59-1.65 (m, 1H), 1.47-1.56 (m, 1H),1.28-1.36 (m, 1H). 13C NMR (CD3SOCD3, 150 MHz) d 170.45, 147.16, 145.40,145.29, 142.53, 134.81, 130.34, 129.72, 126.61, 125.67, 120.63, 118.50, 117.31,109.65, 109.05, 54.80, 41.00, 39.50 (br), 32.16, 30.20, 27.24, 22.44. LC-MScalculated for C22H20N4O [M+ H]+: 357.17, Found: 357.20.

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

Reference:
Article; Maw, Hlaing H; Zeng, Xingzhong; Campbell, Scot; Taub, Mitchell E; Teitelbaum, Aaron M; Drug Metabolism and Disposition; vol. 46; 6; (2018); p. 770 – 778;,
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. 641571-11-1, name is 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline, This compound has unique chemical properties. The synthetic route is as follows., name: 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline

Example 2[69] Synthesis of 4-methyl-N-[3-(4-methylimidazole-l-yl)-5-trifluoromethyl-phenyl] -3-(4-pyrazine-2-yl-pyrimidine-2-yl amino)benzamide[70][71] Method A[72] A pale yellow solid final compound (18.7g, yield 85%) was obtained by reacting3-(4-methyl-imidazole-l-yl)-5-trifluoromethyl-phenylamine (1Og, 41.46mmol) with 4-methyl -3-(4-pyrazine-2-yl-pyrimidine-2-yl amino)-benzoic acid ethyl ester in a similar manner as described in Method A of Example 1, except that 4-methyl-3-(4-pyrazine-2-yl-pyrimidine-2-yl amino) -benzoic acid ethyl ester (15.3g, 45.60mmol) was used, instead of 4-methyl-3-(4-thiazole-2-yl-pyrimidine-2-yl amino)benzoic acid ethyl ester.[73] 1H-NMR(DMSOd , delta= 2.21(s,3H), 2.38(s,3H), 7.35(s,lH), 7.39(s,lH), 7.54(s,lH),7.63(d,lH), 7.75(d,lH), 8.14(d,2H), 8.38(d,2H), 8.54(d,2H), 8.68(s,lH), 9.06(s,lH), 9.45(s, IH), 10.56(s,lH)

According to the analysis of related databases, 641571-11-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; IL-YANG PHARM. CO., LTD.; KIM, Dong Yeon; CHO, Dae Jin; LEE, Gong Yeal; KIM, Hong Youb; WOO, Seok Hun; WO2010/18895; (2010); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

These common heterocyclic compound, 37148-86-0, name is 4-(4-(Trifluoromethyl)phenyl)-1H-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. SDS of cas: 37148-86-0

Sodium hydride (60% in oil) (32 mg) was added at 0 C. to a DMF (6.7 mL) solution of Reference Example 2 (0.17 g), and the mixture was stirred at 0 C. for 30 minutes. 2-Fluoro-4- (trifluoromethyl) benzonitrile (0.13 g) was added to the reaction solution at 0 C., and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with a saturated saline solution and dried over sodium sulfate. After evaporation of the solvent of the organic layer after drying under reduced pressure, the obtained residue was purified by silica gel chromatography (elution solvent; hexane: ethyl acetate) to obtain Reference Example 5 (0.18 g).

The synthetic route of 4-(4-(Trifluoromethyl)phenyl)-1H-imidazole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUMITOMO DAINIPPON PHARMA COMPANY LIMITED; ISOBE, YOSHIAKI; BAN, HITOSHI; SAITO, YASUHIRO; WATANABE, HITOSHI; (44 pag.)JP2018/135270; (2018); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 939-70-8, 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 939-70-8 as follows.

General procedure: To the solution of 2-acetyl benzimidazole 1 (0.01 mol) in MeOH (20 mL) was added 10% aqueous NaOH (2 mL) at 0C with stirring. Then, the solution of aromatic aldehydes (0.01 mol) in MeOH was added drop-wise. The reaction mixture was magnetically stirred for 12 h. After completion of the reaction (monitored by TLC) the reaction mixture was poured over crushed ice. The separated solid was filtered, washed with water and dried. The residue was purified by column chromatography (silica gel with 10% ethyl acetate in petroleum ether) to afford pure benzimidazole derived chalcone 2a-m.

According to the analysis of related databases, 939-70-8, the application of this compound in the production field has become more and more popular.

Reference:
Article; Meshram, Gangadhar A; Vala, Vipul A.; Wagh, Pramod A.; Deshpande, Shruti S.; Indian Journal of Chemistry – Section B Organic and Medicinal Chemistry; vol. 55B; 5; (2016); p. 613 – 623;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 15469-97-3, 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. 15469-97-3 name is 1-Trityl-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.

(i) (2R)-1-(benzyloxy)-3-(1-trityl-1H-imidazol-2-yl)-2-propanol In an argon atmosphere, n-butyllithium (1.6 M solution in hexane, 6.9 ml) was added drop by drop to a solution of 1-tritylimidazole (3.10 g) in THF (80 ml) under ice cooling. After stirring at the same temperature for 30 minutes, (R)-2-[(benzyloxy)methyl]oxirane (1.52 ml) was added. After stirring under ice cooling for 1.5 hours and at room temperature for 1 hour, water was added and the reaction mixture was extracted with ethyl acetate. The extract was washed with water and saline and dried over magnesium sulfate, after which it was concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: ethyl acetate-hexane 1:1) to yield the titled compound (1.402 g) as a pale-yellow oily substance. 1H-NMR (CDCl3) delta: 2.06 (2H, dd, J=2.8 Hz, 18.0 Hz) 3.08 (1H, dd, J=5.4 Hz, 9.8 Hz), 3.21 (1H, dd, J=5.4 Hz, 9.8 Hz), 3.55-3.7 (1H, m), 4.36 (2H, s), 6.73 (1H, d, J=1.4 Hz), 6.93 (1H, d, J=1.4 Hz), 7.0-7.4 (20H, m).

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

Reference:
Patent; Tasaka, Akihiro; Hitaka, Takenori; Matsutani, Etsuya; US2002/173526; (2002); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 870837-18-6, 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. 870837-18-6, name is 3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

t-BuLi (0.188 ml_, 0.32 mmol, 1.7 M) was added dropwise to a solution of compound D6 ((S), R6 = H, R7 = Ph; 46 mg, 0.21 mmol) in THF (1.5 ml_) at -78 0C. The mixture was stirred for 45 minutes before compound D7 (R10 = 3-MeO- Phenyl, R9 = 4-(4-methylimidazol-1-yl)) was added in THF (1.0 ml_) in fast drops. The resulting mixture was stirred for 2 hours before it was diluted with EtOAc (50 ml_) and NH4CI solution (10 mL). The organic layer was washed with brine, dried over MgSO4, and concentrated to give the crude product which was purified by column chromatography eluting with EtOAc/hexanes to yield compound D8 ((S), R6 = H, R7 = Ph; R10 = 3-MeO-Phenyl, R9 = 4-(4-methylimidazol-1 -yl)).

The synthetic route of 3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SCHERING CORPORATION; WO2008/153793; (2008); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

288-32-4, name is 1H-Imidazole, 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. Safety of 1H-Imidazole

Synthesis of 1-benzylimidazole 9 illustrated by step (a) of FIG. 3. (0085) According to the selected experimental protocol, 44 g of imidazole (0.65 mol.), 100 g of benzyl chloride (0.78 mol.), and 60 g of KOH (1.07 mol.) in 700 ml of THF are placed in a 1-liter balloon flask. The reaction mixture is brought to reflux for 120 h, then cooled at ambient temperature. The organic phase is filtered and the solvent is evaporated under reduced pressure. The obtained solid product is dissolved in 500 ml of CH2Cl2, then washed with water (3¡Á100 ml). The organic phase is dried on Na2SO4, filtered, then evaporated under reduced pressure. The collected solid is recristallized in toluene to yield 67 g of desired product.

The synthetic route of 288-32-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Peugeot Citroen Automobiles SA; CNRS (Centre National de la Recherche Scientifique); Glipa, Xavier; Ameduri, Bruno; Delon, Louis; Jones, Deborah; Roziere, Jacques; Frutsaert, Guillaume; US8859160; (2014); B2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 1003-21-0,Some common heterocyclic compound, 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, molecular formula is C4H5BrN2, 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: Ethyl 2-chloro-2-oxoacetate (8.19 g, 60.0 mmol) was added dropwise over 20 min to the corresponding imidazole (60.0 mmol) in CH2Cl2 (500 mL) at -20 C. Then, DIPEA (7.75 g, 10.5 mL, 60.0 mmol) was added at -20 C, the mixture was warmed up to rt and stirred for 12 h. The resulting mixture was washed with H2O (3 ¡Á 150 mL), the organic layer was dried over Na2SO4 and evaporated in vacuo [50]. 4.2.1 Ethyl 2-(5-bromo-1-methyl-1H-imidazol-2-yl)-2-oxoacetate (10h) (0013) Yield 15.0 g (96%); yellowish oil. 1H NMR (500 MHz, CDCl3) delta 7.32 (s, 1 H), 4.46 (q, J =7.1 Hz, 2 H), 4.02 (s, 3 H), 1.41 (t, J =7.1 Hz, 3 H). 13C NMR (126 MHz, CDCl3) delta 176.5, 163.2, 140.9, 132.6, 114.8, 62.6, 33.9, 14.0. LC/MS (CI): m/z = 261/263 [M+H]+. Anal. Calcd. for C8H9BrN2O3: C 36.80; H 3.47; N 10.73; Br 30.61. Found: C 36.66; H 3.65; N 10.58; Br 30.53.

The synthetic route of 1003-21-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Geraschenko, Oleksandr V.; Solomin, Vitalii V.; Vashchenko, Bohdan V.; Khodakivskyi, Pavlo; Tolmachev, Andrey A.; Grygorenko, Oleksandr O.; Journal of Fluorine Chemistry; vol. 229; (2020);,
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. 96797-15-8, name is 4-Iodo-1-trityl-1H-imidazole, A new synthetic method of this compound is introduced below., Computed Properties of C22H17IN2

Compound 1 (2.2 g, 5.0mmol), o-formylphenylboronic acid(1.2 g, 7.5mmol), K3PO4 (3.2 g, 15mmol), Pd (PPh3)4 (0.6 g, 1.0mmol) is dissolved in DMF/H20 (30mL/6mL). The system is replaced with nitrogen and warmed at 90C, the reaction is stirred overnight. The reaction solution is diluted with ethyl acetate (50mL), wash with saturated brine (25mL X 3), dry over anhydrous sodium sulfate, and dry under reduced pressure. Crude column chromatography (PE: EA = 5:1), and then obtained brown solid compound 2 (810 mg, 39%).

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; Lunan Pharmaceutical Group Co., Ltd.; Zhang Guimin; Guan Yongxia; Li Xin; (15 pag.)CN107556315; (2018); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

3304-70-9, name is Dimethyl 4,5-imidazoledicarboxylate, 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. Safety of Dimethyl 4,5-imidazoledicarboxylate

1H-Imidazole-4,5-dicarboxylic acid dimethyl ester (2 g, 10.87 mmol, 1 equiv. ) was dissolved in THF (55 mL, 0.2 M) and DMAP (1.46 g, 11.95 mmol, 1.1 equiv. ) before Di- tert-butyl dicarbonate (3.50 g, 16.29 mmol, 1.4 equiv. ) was added. The reaction was stirred for 16 hours before being quenched with saturated NH4Cl (30 mL) and extracted with ethyl acetate (2 x 30 mL) and the organic layer washed several times with water (4 x 30 mL), brine solution (50 mL). It was dried over Na2SO4, filtered and concentrated in vacuo. Imidazole-1,4,5-tricarboxylic acid 1-tert-butyl ester 4,5-dimethyl ester 252 (3.85 g, 100%, 10.87 mmol). 1H NMR (300 MHz) CDCl3 delta 8.02 (s, 1 H), 3.99 (s, 3 H), 3.92 (s, 3 H). MS: 306.8 (M+23). TLC Rf: 0.6 Hexanes/Ethyl acetate (1/1)

The synthetic route of 3304-70-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Gilead Sciences, Inc.; WO2004/35576; (2004); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem