Author: Jessica.F

Synthetic Route of 360-97-4, 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. 360-97-4 name is 4-Amino-1H-imidazole-5-carboxamide, 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.

A solution of 5-amino-1H-imidazole-4-carboxamide (820mg, 6.5mmol), compound 40a (1.83 mg,6.5 mmol), and Et3N (3 mL) in dry acetonitrile (40 mL) was heated at 50 C for 16 h. After cooling,The brown solid precipitated was collected by filtration and washed with H2O to affordcompound 40b (433 mg, 37%) without further purification.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Amino-1H-imidazole-5-carboxamide, and friends who are interested can also refer to it.

Reference:
Article; Bai, Gang; Cai, Shi; Chen, Yun; Ding, Jian; Duan, Wenhu; Ning, Yi; Song, Peiran; Xie, Hua; Zhang, Huibin; Zhang, Tao; Zhou, Jinpei; European Journal of Medicinal Chemistry; vol. 190; (2020);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 32673-41-9, A common heterocyclic compound, 32673-41-9, name is 4-Imidazolemethanol hydrochloride, molecular formula is C4H7ClN2O, 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.

Step A 4-(Hydroxymethyl)-1-(triphenylmethyl)imidazole To a solution of 4-(hydroxymethyl)imidazole hydrochloride (35.0 g, 260 mmol) in dry DMF (250 mL) at room temperature was added triethylamine (90.6 mL, 650 mmol). A white solid precipitated from the solution. Chlorotriphenylmethane (76.1 g, 273 mmol) in DMF (500 mL) was added dropwise. The reaction mixture was stirred for 20 hrs, poured over ice, filtered, and washed with ice water. The resulting product was slurried with cold dioxane, filtered, and dried in vacuo to provide the titled product as a white solid.

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; Merck & Co., Inc.; US6410534; (2002); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application 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.

To the solution of compound 113-lc (500 mg, 3.4 mmol, 1 eq) in DMF (2.5 mL) was added NaH (163 mg, 4.1 mmol, 60% purity, 1.2 eq) at 0 C. The mixture was stirred at 0 C for 30 min. Then compound 113-lb (460 mg, 3.7 mmol, 351 uL, 1.1 eq) was added to the mixture. The solution was warmed up to 20 C and stirred for 16 hr. The reaction was monitored by LCMS. LCMS showed that the starting material remained and the desired MS was observed. H20 (20 mL) was added to the solution. The mixture was extracted with EtOAc (20 mL*3). The combined organic layer was dried with Na2SC>4 and concentrated under reduced pressure. The residue was purified by to give compound 113-la (100 mg, 528.95 umol, 15.55% yield). It was confirmed by HNMR and HMBC. lH NMR (400MHz, CDC13) delta 7.41 (d, J= 1.3 Hz, 1H), 6.93 (d, J = 1.5 Hz, 1H), 4.37 – 4.27 (m, 1H), 1.48 (d, J= 6.8 Hz, 6H).

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:
Patent; VIVACE THERAPEUTICS, INC.; KONRADI, Andrei W.; LIN, Tracy Tzu-Ling Tang; (294 pag.)WO2019/40380; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 39070-14-9, 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. 39070-14-9, name is (1-Methyl-2-nitro-1H-imidazol-5-yl)methanol, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: The corresponding hydroxy startingcompound (1a, 2a and 3a) (2 mmol) in tetrahydrofuran (10 mL) was added to phosgene (4 mL,8 mmol) and tetrahydrofuran (THF) (15 mL) at 0 C. The reaction mixture was stirred for 16 h, then the solvent was removed in vacuo. The crude chloroformate was used without further purification.

The chemical industry reduces the impact on the environment during synthesis (1-Methyl-2-nitro-1H-imidazol-5-yl)methanol. I believe this compound will play a more active role in future production and life.

Reference:
Article; Anduran, Emilie; Aspatwar, Ashok; Bua, Silvia; Dubois, Ludwig; Lambin, Philippe; Nocentini, Alessio; Parkkila, Seppo; Parvathaneni, Nanda-Kumar; Supuran, Claudiu T.; Suylen, Dennis; Winum, Jean-Yves; Molecules; vol. 25; 10; (2020);,
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Imidazole | C3H4N2 – PubChem

These common heterocyclic compound, 1848-84-6, name is 2-Ethyl-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. SDS of cas: 1848-84-6

A mixture of [2-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)-ethyl]- (l,l-dioxo-tetrahydro-l-thiophen-3-yl)amine (45 mg, 0.11 mmol), 2-ethylbenzimidazole (18 mg, 0.12 mmol), Pd2(dba)3 (2.5 mg, 2.5 molpercent), Xphos (5.2 mg, 10 molpercent) and Cs2CO3 (53 mg, 0.16 mmol) in dioxane (1.5 mL) was purged with argon gas then heated at 120 °C, for 4 h, in a sealed tube. The reaction mixture was loaded onto an Isolute.(R). SCX-2 cartridge, washed with MeOH then the desired product eluted with 2 M NH3/MeOH in DCM. The resulting residue was purified by column chromatography (Si-PCC, 0-10percent MeOH in DCM) to give 595 (35 mg, 62percent) as a pale yellow solid. LCMS: (Method I): Rx 2.43 min, [M+H]+ 525.2 1H NMR (300 MHz, CDCl3d): delta 8.02-7.98 (m, 1 H), 7.78-7.74 (m, 1 H), 7.31-7.23 (m, 2 H), 4.50-4.95 (m, 4 H), 3.87 (t, J = 4.7 Hz, 4 H), 3.76 (s, 3 H), 3.73-3.67 (m, 1 H), 3.40- 3.24 (m, 4 H), 3.23-3.14 (m, 2 H), 3.14-3.00 (m, 4 H), 2.94 (dd, J = 13.2, 6.0 Hz, 1 H), 2.49- 2.45 (m, 1 H), 2.15-2.05 (m, 1 H), 1.44 (t, J = 7.5 Hz, 3 H)

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

Reference:
Patent; GENENTECH, INC.; F. HOFFMANN-LA ROCHE AG; CASTANEDO, Georgette; CHAN, Bryan; GOLDSTEIN, David Michael; KONDRU, Rama K.; LUCAS, Matthew C.; PALMER, Wylie Solang; PRICE, Stephen; SAFINA, Brian; SAVY, Pascal Pierre Alexandre; SEWARD, Eileen Mary; SUTHERLIN, Daniel P.; SWEENEY, Zachary Kevin; WO2010/138589; (2010); A1;,
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. 583-39-1, name is 2-Mercaptobenzimidazole, A new synthetic method of this compound is introduced below., Quality Control of 2-Mercaptobenzimidazole

a. A mixture of 0.46 g (0.0016 mol) of benzyl acetate 6, 0.25 g (0.0016 mol) of 1,3-dihydrobenzimidazole-2-thione, 3 mL of acetone, and 3 mL of formic acid was heated at 40C for 6 h. The reaction mixture was cooled down to ambient temperature and poured into aqueous NaCl. The precipitate that formed was filtered off, washed with water, and dried in air. Yield 0.56 g (92%), mp 168-170C (benzene). 1H NMR spectrum (CDCl3), delta,ppm: 1.34 s (18H, CMe3), 4.73 s (2H, CH2N), 5.23 s(1H, OH), 7.17 s (2H, ArH), 7.23-7.30 m (2H, H5,6),7.71-7.78 m (2H, H4,7). Found, %: C 71.45; H 7.83; N 7.27. C22H28N2OS. Calculated, %: C 71.70; H 7.66; N 7.60. b. A solution of benzyl acetate 6 and 1,3-dihydrobenzimidazole-2-thione in a 1 : 1 mixture of acetone and formic acid at ambient temperature for 2 days to obtain 98% of compound 12.

The synthetic route of 583-39-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Tagasheva; Gataullina; Zaripova; Bukharov; Nugumanova; Deberdeev; Voronina, Yu. K.; Russian Journal of General Chemistry; vol. 87; 1; (2017); p. 22 – 28; Zh. Obshch. Khim.; vol. 87; 1; (2017); p. 26 – 32,7;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 106429-59-8,Some common heterocyclic compound, 106429-59-8, name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, molecular formula is C8H6N2O2, 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.

Step 3.5-((7-(5-(4-fluoro-2-(3-hydroxypentan-3-yl)phenoxy)pyrimidin-4-yl)-2,7- diazaspiro[4.4]nonan-2-yl)methyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (0942) To a solution of crude 3-(2-((4-(2,7-diazaspiro[4.4]nonan-2-yl)pyrimidin-5- yl)oxy)-5-fluorophenyl)pentan-3-ol from above and 2-oxo-2,3-dihydro-1H- benzo[d]imidazole-5-carbaldehyde (Intermediate 40, 20 mg, 0.12 mmol) in MeOH (3 mL) was added NaBH3CN (10 mg, 0.16 mmol) at RT and the reaction mixture stirred for 4 h. Evaporation of the solvent followed by RP-HPLC method A afforded 5-((7-(5-(4- fluoro-2-(3-hydroxypentan-3-yl)phenoxy)pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2- yl)methyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one. LCMS method G: Rt = 3.197 min; (M+H)+ = 547.61.1H NMR (CD3OD): delta 8.52 (bs, 1H), 7.60 (m, 1H), 7.45 (dd, J = 2.8, 10.6 Hz, 1H), 7.21-7.18 (m, 2H), 7.11 (d, J = 8.4 Hz, 2H), 7.05-6.96 (m, 1H), 4.43 (s, 2H), 4.20-3.90 (m, 4H), 3.70-3.50 (m, 2H), 3.48-3.33 (m, 2H), 2.34-1.90 (m, 6H), 1.89- 1.80 (m, 2H), 0.78 (t, J = 7.2 Hz, 6H).

The synthetic route of 106429-59-8 has been constantly updated, and we look forward to future research findings.

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

1243204-92-3, name is 3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)benzonitrile, 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. COA of Formula: C12H11N3O

3-Methoxy-4-(4-methyl-lH-imidazol-l-yl)benzonitrile (100 mg, 0.469 mmol) was placed in a reaction vessel, and a 5 M aqueous sodium hydroxide solution (1 mL) and methanol (2 mL) were successively added to the vessel. The resultant mixture was stirred at room temperature for 2 hours, and then further stirred at 65C for 5 hours. The resultant reaction mixture was concentrated under a reduced pressure, and a 2 M aqueous hydrochloric acid solution (4 mL) and water (4 mL) were successively added to the concentrate. The solids collected by filtration were dried under a reduced pressure to obtain 98 mg of a title compound. Yield: 78%.

The synthetic route of 1243204-92-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Eisai R&D Management CO., LTD.; YOSHIKAWA, Seiji; KAYANO, Akio; WO2011/37244; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 33468-69-8, 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 33468-69-8 as follows.

Sodium hydride (7.91 mg, 0.198 mmol, 60% in mineral oil) was added to a solution of 4- (trifluoromethyl)-I H-imidazole (24.46 mg, 0.180 mmol) in dry N,N-dimethylformamide (0.4 ml). The reaction was stirred at room temperature for 30 minutes until gas evolution ceased. A solution of 2-(5- bromo-4-methyl-1 ,2,4-triazol-3-yl)-3-ethylsulfanyl-5-(trifluoromethyl)pyridine (66.0 mg, 0.180 mmol) in N,N-dimethylformamide (2.0 ml) was slowly added and the reaction mixture stirred at room (0511) temperature for 30 minutes. Two more equivalents of the previously described solution consisting of sodium hydride and 4-(trifluoromethyl)-1 H-imidazole were then added and stirring continued overnight at 60C. The mixture was quenched over water and ethyl acetate, the layers separated, the aqueous phase extracted twice with ethyl acetate, the combined organic phases dried over sodium sulfate and concentrated. The residue was purified over silica by flash column chromatography (cyclohexane/ethyl acetate) to afford 3-ethylsulfanyl-2-[4-methyl-5-[4-(trifluoromethyl)imidazol-1-yl]-1 ,2,4-triazol-3-yl]-5- (trifluoromethyl)pyridine (compound P2) as a solid (55 mg). LCMS (method 4): 423 (M+H)+, retention time 0.97 min. H-NMR (CDCb, ppm) 8.70 (t, 1 H), 8.00 (d, 1 H), 7.94 (d, 1 H), 7.71 (m, 1 H), 3.81 (s, 3H), 3.06 (q, 2H), 1.42 (t, 3H).

According to the analysis of related databases, 33468-69-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SYNGENTA PARTICIPATIONS AG; JUNG, Pierre, Joseph, Marcel; MUEHLEBACH, Michel; EDMUNDS, Andrew; RENOLD, Peter; BUCHHOLZ, Anke; (96 pag.)WO2018/41729; (2018); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 4857-06-1, 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. 4857-06-1 name is 2-Chloro-1H-benzo[d]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.

2-Chloro-5,6-dibromobenzimidazole (17) To a suspension of 0.763 g (5 mmole) of 2-chlorobenzimidazole in 50 mL of 1:1 MeOH/H2 O, was added dropwise a solution of 1 mL of Br2 in 10 mL of MeOH over a period of 30 min. The reaction mixture was stirred at room temperature overnight and was then filtered. The solid was washed with portions of H2 O until the washings were neutral. This solid was air dried and recrystallized from MeOH to give 1.115 g (3 crops, 72%) of 17. mp 228 C.; 1 H NMR (DMSO-d6) d 13-14 (br. s, 1,1-NH), 7.93 (s, 2,4-H, 7-H).

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

Reference:
Patent; The Regents of the University of Michigan; US5360795; (1994); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem