Month: March 2021

Adding a certain compound to certain chemical reactions, such as: 5465-29-2, name is 2-Propylbenzimidazole, 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 5465-29-2, COA of Formula: C10H12N2

General procedure: To a solution of [DodecIm][HSO4]* (5.00 mol%, 16.7 mg) in 95% EtOH (5.00 mL) was added aldehyde (2) (1.00 mmol) and o-phenylenediamine (1a) (1.20 mmol, 129.8 mg) or 2-amino-4-fluoroaniline (1c) (1.20 mmol, 151.2 mg) at room temperature respectively. The reaction mixture was stirred at room temperature for 12 h and then ethanol solvent was removed by rotary evaporator. The crude residue was diluted with water (5.00 mL)No. and extracted with ethyl acetate (3 * 5 mL). The combine organic layer was concentrated using rotary evaporator. Then crude residue was dissolved in acetonitrile (5.00 mL), followed by adding KOH (2.00 mmol, 112 mg) and alkyl halide (2.00 mmol) at room temperature respectively. The reaction mixture was stirred at room temperature for 0.5-24 h. After the reaction completed, the reaction mixture was neutralized with sat. NH4Cl and extracted with ethyl acetate (3 * 15 mL). The combine organic layer was dried over sodium sulfate anhydrous and concentrated using rotary evaporator. The crude product was purified by column chromatography (SiO2, 10-50% ethyl acetate/n-hexane as eluent depend on each derivatives) to give the desired products 5a-5z. *Recycling experiment. After extraction, the water layerNo. was removed to give the catalyst III. Recovered catalyst III was reused directly by adding EtOH and substrates in the next run without purification. Spectral data of compounds 5b [24], 5c [24], 5l [3c], 5o [26], and 5q [25], were previously described in the literature.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Propylbenzimidazole, and friends who are interested can also refer to it.

Reference:
Article; Senapak, Warapong; Saeeng, Rungnapha; Jaratjaroonphong, Jaray; Promarak, Vinich; Sirion, Uthaiwan; Tetrahedron; vol. 75; 26; (2019); p. 3543 – 3552;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 221289-88-9,Some common heterocyclic compound, 221289-88-9, name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile, molecular formula is C8H5N3O, 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 a suspension of 2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile (XVTI, 1.19 g, 7.48 mmol, 1 equiv) in acetonitrile (5 mL) was added phosphorus(v) oxy chloride (1.398 mL, 14.95 mmol). The reaction was stirred at 1 10 C for 16 hours, then cooled to room temperature. It was diluted with acetonitrile and then slowly added to a cold, rapidly -stirring beaker of saturated aqueous sodium bicarbonate (50 mL). The mixture was extracted with ethyl acetate; which was dried over anhydrous magnesium sulfate, filtered, and concentrated to provide 2~chloro-1H-benzo d]imidazole~6-carbonitrile as a tan powder. (ESI, pos. ion) m/z: 178.2 [M+i]

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile, its application will become more common.

Reference:
Patent; AMGEN INC.; BARTBERGER, Michael D.; CHAKKA, Nagasree; GAO, Hua; GUZMAN-PEREZ, Angel; HORNE, Daniel B.; HUA, Zihao; KIEFFER, Madeleine; LIN, Daniel C. H.; MILGRAM, Benjamin Charles; PANTELEEV, Jane; SCHENKEL, Laurie; STELLWAGEN, John; WEISS, Matthew; WHITE, Ryan D.; ZHAO, Wei; (345 pag.)WO2019/79578; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 84946-20-3,Some common heterocyclic compound, 84946-20-3, name is 2-Chloro-1-(4-fluorobenzyl)-1H-benzo[d]imidazole, molecular formula is C14H10ClFN2, 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 4 8-[1-(4-Fluorobenzyl)-1H-benzimidazol-2-yl]-1,4-dioxa-8-azaspiro[4.5]decane (2) A mixture formed by 50 g of 2-chloro-1-(4-fluorobenzyl)benzimidazol, 41 g of 1,4-dioxa-8-azaspiro[4.5]decane and 84 mL of diisopropylethylamine in 350 mL of isoamylic alcohol is heated under reflux for 48 hours. Once the reaction has finished, 175 mL of solvent are distilled and slowly cooled to a temperature of 0-5C so that a white solid precipitates. The precipitate produced is filtered and washed with 75 mL of cold isoamylic alcohol, and is dissolved again in 250 mL of water and 250 mL of ethyl acetate. It is stirred, and the organic phase is isolated by decanting. The product is isolated by removing the solvent under reduced pressure, obtaining 60 g of 8-[1-(4-fluorobenzyl)-1H-benzimidazol-2-yl]-1,4-dioxa-8-azaspiro[4.5]decane (2).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Chloro-1-(4-fluorobenzyl)-1H-benzo[d]imidazole, its application will become more common.

Reference:
Patent; Ragactives, S.L.; EP1564212; (2005); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 144690-33-5, name is Ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-((2′-(1-trityl-1H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylate, 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 144690-33-5, name: Ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-((2′-(1-trityl-1H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylate

20L reactor was added 300.0g (1.25mol) imidazole mono-, 1043.6g (1.87mol) BBTT, 44.8g (1.87mol) of lithium hydroxide and 7kg acetonitrile. The reaction system was increased to 70-75 5h, TLC or HPLC in control, raw reaction was complete. After cooling to 30-45 system To the system was added in portions 280.6g (5.0mol) of potassium hydroxide and 700g of water to form a solution. Plus complete, insulation reaction 4-5h, TLC or HPLC in control, raw reaction was complete. After 300g of water added to the system dropwise acetic acid adjusted to pH 5.5 to 6.5. After stirring for 1h incubation continued cooling to room temperature, filtered, the filter cake washed with a small amount of acetone to obtain 777.4g of intermediate 5 run. HPLC: 95.9%,Yield: 90.4%.

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, Ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-((2′-(1-trityl-1H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Jiangsu Bang Pharmaceutical Co., Ltd.; Zhao, Guangrong; Huan, Shuang; Zhao, Huayang; Liu, Liping; Chen, Guoping; Tang, Jingyu; (19 pag.)CN105481842; (2016); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 152628-03-0, 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. 152628-03-0, name is 4-Methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows.

The compound IIc (534 mg, 2.45 mmol)Was slowly added to polyphosphoric acid (15 mL) heated to 80 C,Stirred and heated to 150 C.Compound IIIb (320 mg, 2.94 mmol) was added slowly to the former polyphosphoric acidAfter the addition was complete, the reaction was stirred at 150 C for 12 h. After completion of the reaction, the reaction solution was poured into 100 mL of ice water,And adjust the pH to 8-10 with concentrated ammonia, there will be a large number of precipitation, filtration, filter cake with 5% ethanol solution washed three times. To be filteredAfter drying the cake, the resulting filter cake was purified by chromatography to give about 357 mg (yield 58.7%) of the pale yellow compound IVb.

The chemical industry reduces the impact on the environment during synthesis 4-Methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylic acid. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Donghua University; Chen Zhilong; Bao Xiaolu; Zhu Weibo; Wu Zhuo; Zhang Ruijing; Ren He; Zhang Jinyan; Zhu Xingbo; Zhou Huayuan; Tang Hesheng; Yu Xinhai; Yan Yijia; (15 pag.)CN106749220; (2017); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 934-32-7, 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. 934-32-7 name is 1H-Benzo[d]imidazol-2-amine, 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: In a typical experiment, different aromatic aldehyde (1 mmol),1,3-cyclic diketon (1 mmol), 2-amino-benzimidazole (1 mmol) andcatalyst (0.019 g) in solvent free condition were taken in a 25 mLround bottomed flask. The flask was stirred at 100C for an appro-priate time. The reaction mixture was cooled, eluted with hotethanol (5 mL), centrifuged and filtrated to collect the formed pre-cipitate. The crude product was recrystallized from ethanol to yieldpure benzimidazoloquinazolinone derivatives.

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

Reference:
Article; Amoozadeh, Ali; Rahmani, Salman; Journal of Molecular Catalysis A: Chemical; vol. 396; (2015); p. 96 – 107;,
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. 3304-70-9, name is Dimethyl 4,5-imidazoledicarboxylate, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C7H8N2O4

EXAMPLE VI Dimethyl 2-bromo-1H-imidazole-4.5-dicarboxylate 6.11 ml bromine are added to 19.80 g dimethyl 1H-imidazole4,5-dicarboxylate and 14.92 g potassium carbonate in 600 ml methylene chloride. The reaction mixture is stirred for one hour at ambient temperature, then a mixture of saturated sodium sulphite solution and saturated sodium chloride solution (1:1) is added. The organic phase is largely separated off and the aqueous phase is extracted with ethyl acetate several times. The combined organic phases are dried over magnesium sulphate and evaporated down, leaving about 7.40 g crude product. The aqueous phase is combined with ethyl acetate and extracted overnight in an extraction apparatus. The ethyl acetate extract is evaporated down and the flask residue is combined with the crude product already obtained. Yield: 13.10 g (46% of theory) Mass spectrum (ESI+): m/z=263, 265 [M+H]+

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 3304-70-9.

Reference:
Patent; Boehringer ingelheim international GmbH; US2005/26921; (2005); 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. 89830-98-8, name is 5-Cyclopropyl-1H-imidazole, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 5-Cyclopropyl-1H-imidazole

Step 2: 2-(4-cyclopropyl-1H-imidazol-1-yl)-9-(oxazol-5-yl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one A mixture of 9-(oxazol-5-yl)-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione (180 mg, 0.61 mmol) in DCE (10 mL) was treated with POCl3 (114 muL, 1.22 mmol) and heated to 100¡ã C. for 1 h. The mixture was then allowed to cool to RT, poured onto cold H2O and extracted with DCM. The org. phases were dried over Na2SO4, filtered and concentrated in vacuo. The brown residue obtained was taken up in DCE (5 mL) and 4-cyclopropyl-1H-imidazole (79 mg, 0.73 mmol) and pyridine (148 muL, 1.83 mmol) were then added. The mixture was heated to 100¡ã C. for 1 h, and then allowed to cool to RT, poured onto H2O and extracted with DCM. The org. layers were then dried over Na2SO4, filtered and concentrated in vacuo. Purification by SFC (column: 2-Ethylpyridine 5 mum, 250*30 mm, 60A, Princeton; eluent: 9percent MeOH/CO2 for 1 min, then from 9percent MeOH/CO2 to 14percent MeOH/CO2 in 6 min; then from 14percent MeOH/CO2 to 50percent MeOH/CO2 in 1 min; flow 100 mL/min; UV detection at 220 nm) afforded the title compound (7 mg) as pale brown solid. UPLC-MS: MS 386.1 (M+H+); UPLC rt 0.79 min. 1H NMR (400 MHz, CHLOROFORM-d): delta ppm 0.78 (m, 2H); 0.81-0.87 (m, 2H); 1.79-1.93 (m, 1H); 3.14 (t, J=6.02 Hz, 2H); 3.94 (t, J=6.15 Hz, 2H); 4.38 (br. s., 2H); 6.66 (s, 1H); 7.20 (s, 1H); 7.30 (s, 1H); 7.42-7.60 (m, 1H); 7.77 (d, J=7.78 Hz, 1H); 7.74 (d, J=8.03 Hz, 1H); 7.90 (s, 1H); 8.03 (s, 1H).

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 89830-98-8.

Reference:
Patent; NOVARTIS AG; BEHNKE, Dirk; CARCACHE, David; ERTL, Peter; KOLLER, Manuel; ORAIN, David; US2014/57902; (2014); 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. 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., Application In Synthesis of 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline

Example-19: Preparation of Nilotinib : In 3 lit four necked round bottom flask equipped with mechanical stirrer, thermometer, reflux condenser and an addition funnel, 4-methyl-3-{[4-(3-pyridinyl)-2- pyrimidinyl] amino (benzoic acid (100 g) and N-methyl-2-pyrrolidone (750 ml) was added under nitrogen atmosphere at 25-35C and heated to 60-65C. To this, thionylchloride (30 ml) was added at 60-65C and stirred for 3 hrs at the same temperature. After completion of reaction, a solution of 3 -(4-methyl- lH-imidazol-1- yl)-5-(trifluoromethyl)aniline (86.6 g) in N-methyl-2-pyrrolidone (150 ml) was added to the reaction mass at 60-65C over a period of 45 mins. The reaction mass was further heated to 90-95 C and stirred for 5 hrs at the same temperature. After completion of reaction, the reaction mass was cooled to 75-85C and water (1000 ml) was added to it over a period of 60 mins. Then reaction mass basified with aqueous sodium hydroxide solution at 75-85C; cooled to 35-45C and then stirred for 2 hrs. The reaction mass was further cooled to 5-l0C and stirred for 3 hrs. The solid obtained was filtered, washed with water and dried under vacuum for 12 hrs at 60- 65C to get the title compound. Yield: 145 g.

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 641571-11-1.

Reference:
Patent; LAURUS LABS LTD; BOLLU, Ravindra Babu; BANDLAMUDI, Veera Narayana; KUDIRILLA, Vivek Kumar; VEMULA, Rambabu; VASIREDDI, Uma Maheswer Rao; (36 pag.)WO2019/130254; (2019); 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. 2302-25-2, name is 4-Bromo-1H-imidazole, A new synthetic method of this compound is introduced below., Recommanded Product: 4-Bromo-1H-imidazole

A mixture of 4-methyl-3-(4-(pyridin-2-ylmethoxy)benzamido)phenyl boronic acid (50 mg, 0.14 mmol), Cs2CO3 (135 mg, 0.41 mmol), Pd(PPh3)4(23.93 mg, 0.02 mmol) and 4- bromo-lH-imidazole (26 mg, 0.18 mmol) was purged with nitrogen before adding degassed dioxane (690 muL) and water (230 muL) and heating in a microwave for 40 min at 150 C. After cooling, the aqueous layer was removed with a pipette, and the organic layer was diluted with DMSO (1 mL) and filtered through a 0.2 mum filter. The filtrate was concentrated to a volume of 1 mL and purified by Gilson HPLC (20-75% MeCN/10 mM NH4OAc in water). The fractions were concentrated and lyophilized to yield the title compound (19 mg, 0.049 mmol, 35%). 1U NMR (DMSOd6) 12.11 (s, IH), 9.76 (s, IH), 8.59 (d, IH), 7.97 (d, 2H), 7.85 (td, IH), 7.70 (s, IH), 7.67 (s, IH), 7.56 (m, 2H), 7.36 (dd, IH), 7.21 (d, IH), 7.15 (d, 2H), 5.27 (s, 2H), 2.18 (s, 3H). MS (M+H+) = 385.

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; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2009/27746; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem