Tag: M.W=200-300

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. 84946-20-3 name is 2-Chloro-1-(4-fluorobenzyl)-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. 84946-20-3

Example 4; A/-[3-(1-{3-[1-(4-Fluoro-benzyl)-1H-benzoimidazol-2-ylamino]-propyl}-piperidin-4-yl)-phenyl]-acetamide; 2-Chloro-1-(4-fluoro-benzyl)-1H-benzoimidazole (58 mg, 0.22 mmol) and A/-{3-[1-(3-Amino-propyl)-piperidin-4-yl]-phenyl}-acetamide (Example 1 Step 2, 90 mg, 0.33mmol) were mixed in ethanol (1 ml) and heated in the micro wave at 150 C for 2h.The reaction was extracted with dichloromethane and Na2CO3(aq) and the combinedorganic phases was dried over Na2SO4, filtered, and evaporated giving the crudeproduct which was purified by chromatography (silica,dichloromethane/methanol/ammoniac, 9:1:1%) giving the title compound Example 4.1H-NMR (300 MHz, CDCI3); 8 7.5.1 (d, 1H), 7.38 (s, 1H), 7.10-7.31 (m, 6H), 6.92-7.02(m, 4H), 6.79 (d, 1H), 6.61 (br s, 1H), 5.17 (s, 2H), 3.71 (t, 2H), 3.14 (d, 2H), 2.62 (t,2H), 2.48-2.61 (m, 1H), 2.21 (s, 3H) 2.06-2.15 (m, 2H), 1.91-2.00 (m, 2H), 1.65-1.86(m, 4H).LCMS: Rt 3.48 min, m/z 499.6 [M+].

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-1-(4-fluorobenzyl)-1H-benzo[d]imidazole, and friends who are interested can also refer to it.

Reference:
Patent; 7TM PHARMA A/S; WO2006/10446; (2006); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1450-93-7, Adding some certain compound to certain chemical reactions, such as: 1450-93-7, name is 1H-imidazol-2-amine sulfate(2:1), 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 1450-93-7.

2-Aminoimidazole sulfate (1.53 g) is dissolved in 0.97 mL of concentrated HCI, 1 mL of water, and 3 mL of acetic acid. The resulting solution is cooled to 0 oC. A solution 799 mg of NaN02 in 2 mL of water is added dropwise, and the internal temperature is maintained below 5C. The resulting yellow-brown solution is stirred for 30 minutes at 0 o20 C. In a separate flask equipped with a mechanical stirrer a mixture of 1.65 g of 1, 4-diallyl-l, 2,3, 4- tetrahydroquinoxaline, 1.9 g of sodium acetate and 10 mL of acetic acid is cooled to 0 C. The diazonium solution is added slowly to this slurry while stirring. After the addition is complete, the resulting red suspension is stirred for 1 hour at 0 oC. The dark reaction mixture is poured into a beaker containing 10 g of ice. Aqueous NaOH (20%) is added to the suspension slowly until pH 6.5 is reached. The mixture is filtered and the dark solid is dried. (E)-6-((lH-imidazol- 2-yl)diazenyl)-l,4-diallyl-l,2,3,4-tetrahydroquinoxaline (2.3g) is used in the next step without further purification.

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 1450-93-7.

Reference:
Patent; NOXELL CORPORATION; MURPHY, Bryan Patrick; ZHANG, Guiru; ZHAO, Jielu; (106 pag.)WO2018/53034; (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 3543-73-5 as follows. 3543-73-5

[0079] To a solution of 81.3 g (650.6 mmol) 2-bromoethanol, 1 g potassium iodide and 100 g water was added 17.0g (65 mmol) compound (6). The reaction mixture was heated to 65-70 C and held at this temperature for 8 h to 12 h.The pH value of the solution was held between 4.2-5.5 during this period by dropwise addition of a solution of 20.0 g(151.4 mmol) diammonium hydrogen phosphate in 35 g water. The control of pH over the duration of the reaction waseffected through use of a pH electrode. The conversion was followed by HPLC. The reaction was continued until thefraction of compound (7A) was ? 1.5 %. Thereby ca. 8% of compound (7B) had formed and the proportion of compound(7) was ca. 87%. The reaction mixture was subsequently concentrated to dryness at ca. 55-60 C under vacuum. Tothe residue was added 150 g water and, preferably with an alkali metal carbonate, the pH value adjusted to ca. 8.5. Thedesired product (7) was extracted with 200 g methylene chloride or 225 g chloroform, and the organic phase subsequentlywashed with 60 – 80 g water. The organic phase was then concentrated to dryness and the remaining oil or alreadycrystalline residue dissolved in 200 g ethyl acetate or alternatively in 60 g actetonitrile. Compound (7) crystallised at ca.5 C and was filtered under suction, washed with 20 g cold ethyl acetate or alternatively with 15 g cold acetonitrile anddried at 60 -70 C. The yield of compound (7) was 18.3 g (52.4 mmol) with a content of ? 98.2% (80.5 % of theory). Thecrude product contained ?0.6% compound (7A) and compound (7B) respectively as well as 99.2%, wherein compound (7A)was removed below a content of 0.2 % and compound (7B) below 0.3 %. Through the course of the reaction, the contentof compound (7C) was kept below 0.15 %, as this compound can only poorly be removed by recrystallization from theabove described solvents. The overall yield of this step was 76.5% of theory and was thus ca. 12.5% higher than thatdescribed in the procedure using ethylene oxide as according to DD34727 and ca. 31% higher in comparison to thefavoured procedure of W02011079193 involving addition of Huenig?s base.Example 5: Synthesis of ethyl 4-[5-[bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-

According to the analysis of related databases, 3543-73-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; HEYL Chemisch-Pharmazeutische Fabrik GmbH und Co. KG; Frey, Michael; Walther, Dirk-Detlef; EP2690096; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

152628-03-0, 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. 152628-03-0, name is 4-Methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylic acid belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Preparation 1 7-Methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid ((R)-1-benzyl-2-benzyloxycarbamoylethyl)amide To a solution of 7-methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid (164 mg, 752 mumol) and (R)-3-amino-N-benzyloxy-4-phenylbutyramide (TFA salt: 300 mg, 754 mumol) in DMF (10 mL) containing triethylamine (210 muL), was added HOBt (151 mug, 755 mumol) and EDC (151 mg, 788 mumol). The mixture was stirred at room temperature overnight and concentrated in vacuo, yielding a pale brown residue. The residue was dissolved in DCM (100 mL) and washed sequentially with 1M H3PO4, a saturated NaHCO3 solution, and saturated aqueous NaCl. The organic layer was collected, dried over MgSO4, and concentrated to afford the title compound as a pale yellow oil (150 mg; 41% yield), which was used without further treatment. ESMS [M+H]+ calcd for C29H32N4O3, 485.26; found 485.5.

The synthetic route of 4-Methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Choi, Seok-Ki; Fatheree, Paul R.; McKinnell, Robert Murray; Olson, Brooke; US2009/149521; (2009); A1;,
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. 641571-11-1

To a solution of 3 (500 mg, 2.1 mmol) and 48 (489 mg, 2.1 mmol) in CH2CI2 (10mL) was added pyridine (242 mg, 3.1 mmol), dropwise. The reaction was stirred atroom temperature overnight. Water was added and the mixture was extracted with CH2CI2 twice. The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography to give 49 (180 mg, 20%) as a slightly yellow solid. LCMS (m/z: m+1): 441 .1.

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:
Patent; CARDIO THERAPEUTICS PTY LTD; TREUTLEIN, Herbert; ZENG, Jun; DIXON, Ian; JAMES, Ian; PALMER, James T; (169 pag.)WO2018/165718; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

144689-93-0, Adding a certain compound to certain chemical reactions, such as: 144689-93-0, name is Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-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 144689-93-0.

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%.

According to the analysis of related databases, 144689-93-0, the application of this compound in the production field has become more and more popular.

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

144689-93-0, The chemical industry reduces the impact on the environment during synthesis 144689-93-0, name is Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate, I believe this compound will play a more active role in future production and life.

400 ml of acetone was added to a 1 L glass reaction flask, and 111. 4 g of N-(triphenylmethyl)-5-(4′-bromomethylbiphenyl-2-yl)tetrazole, 48.0 of ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazol-5-carboxylate was added with stirring, 55.2 g of potassium carbonate, 6.4 g of tetrabutylammonium bromide, heated to 50-60 C, After the incubation reaction for 20 hours, the temperature was lowered to 20-30 C, 200 ml of water was added, stirred for 30 minutes, and filtered, and the filter cake was successively rinsed with 200 ml of water and 200 ml of acetone. The filter cake was air-dried at 40-50 C for 12 hours to give a white solid, 130.0 g ( Intermediate 1), yield: 90.7%, HPLC: 98.6%.

The chemical industry reduces the impact on the environment during synthesis Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Jiashi (Hunan) Pharmaceutical Technology Co., Ltd.; Dai Yongzhi; Liu Hu; Zhu Laifa; Cai Jian; (8 pag.)CN108341804; (2018); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

113775-47-6, A common compound: 113775-47-6, name is Dexmedetomidine, belongs to imidazoles-derivatives compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

A mixture of (+)-(S)-4-[1-(2,3-dimethyl-phenyl)-ethyl]-1H-imidazole (dexmeditomidine; 2.00 g, 10.0 mmol) prepared as described in Cordi et al., Synth. Comm. 26: 1585 (1996), in THF (45 mL) and water (40 mL) was treated with NaHCO3 (8.4 g, 100 mmol) and phenylchlorothionoformate (3.7 mL, 27.4 mmol). After stirring for four hours at room temperature, the mixture was diluted with water (30 mL) and ether (75 mL). The organic layer was removed, and the aqueous layer extracted with ether (2¡Á50 mL). The organic layers were dried over MgSO4 and filtered. The residue was concentrated under vacuum, diluted with MeOH (54 mL) and reacted with NEt3 (6.5 mL) at room temperature for 16 hours. The solvent was removed under vacuum and replaced with 30% CH2Cl2:hexane. The solvent was removed again and solids formed. After further resuspension in 30% CH2Cl2:hexane, the solid was collected on a filter, washed with CH2Cl2:hexane and dried under vacuum to give Compound 1 ((+)-(S)-4-[1-(2,3-dimethyl-phenyl) ethyl]-1,3-dihydro-imidazole-2-thione) 1.23 g (53%). Characterization of the product yielded the following. Optical rotation: [a]D20+14 (c 1.25 in MeOH). 1H NMR: (300 MHz, DMSO) d 11.8 (s, 1H), 11.6 (s, 1H), 7.03-7.01 (m, 2H), 6.95-6.91 (m, 1H), 6.50 (s, 1H), 4.15 (q, J=6.9 Hz, 1H), 2.25 (s, 3H), 2.20 (s, 3H), 1.38 (d, J=6.9 Hz, 3H)

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, Dexmedetomidine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Allergan, Inc.; US2005/59664; (2005); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1080-79-1, These common heterocyclic compound, 1080-79-1, name is Diethyl 1H-imidazole-4,5-dicarboxylate, 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.

A. N-o-Nitrophenylimidazole 4,5-dicarboxylic acid diethyl ester To a solution of o-fluoronitrobenzene (106 g) and imidazole 4,5-dicarboxylic acid diethyl ester (106 g) in one liter of N,N-dimethyl formamide (DMF) was added anhydrous potassium carbonate (200 g). The reaction mixture was stirred vigorously for at least four hours. After removal of solvent under oil pump vacuum, the residue was treated with water, then extracted with chloroform (300 ml*3). The combined chloroform extracts were washed with water, dried by magnesium sulfate, then concentrated under vacuum to an oil. Upon treatment with ether, the oil was solidified and the product was obtained as a white solid (136 g, 81% yield). Recrystallized from chloroform-hexane, m.p. 93-95 C.

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 1080-79-1.

Reference:
Patent; USV Pharmaceutical Corporation; US4440929; (1984); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

A common heterocyclic compound, 144689-93-0, name is Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate, molecular formula is C12H20N2O3, 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. 144689-93-0.

Example 2; Preparation of olmesartan medoxomilTo dimethyl acetamide (600 ml) was added 4-(1-hydroxy-1-methylethyl)-2-propyl imidazol- 5-carboxylic acid ethyl ester (100 gms) and powdered potassium hydroxide (50 gms). To this was charged 4-[2-(trityltetrazol-5-yl)phenyl]benzyl bromide (270 gms) at 45-50C. The contents were stirred for 5 hours at 45-50C. Diisopropylethyl amine (200 ml) was charged to the reaction mass at 40-450C. To this was slowly added a solution of 5-methyl-2-oxo- 1 ,3-dioxane-4-yl)methyl chloride (160 gms) diluted with dimethyl acetamide (320 ml) at 40- 45C over a period of 1 hour. The contents were heated to 60-650C and maintained for 4 hours. The reaction mass was then cooled to 30-350C and was neutralized with concentrated hydrochloride acid. The reaction mass was filtered to remove inorganic impurities. The reaction mass was charcoalized using charcoal (20 gms) and was stirred for 30 minutes at 40-450C. The reaction mass was filtered over hyflo. The clear filtrate was acidified with hydrochloric acid (200 ml) slowly at 25-300C. The contents were stirred at 60C for 1 hour. The reaction mass was chilled to 0-50C and was filtered to remove tritanol. The reaction mass was concentrated under reduced pressure. The residue was quenched with water (1000 ml), neutralized with base and extracted in dichloromethane (1000 ml). The clear dichloromethane extract was then concentrated under reduced pressure, stripped off with acetone. The residue thus obtained was isolated from the acetone (500 ml) to give 110 gms of the title compound. Chromatogrphic purity- > 99%; Example 4Preparation of trityl olmesartan medoxomilTo dimethyl acetamide (300 ml) was added 4-(1-hydroxy-1-methylethyl)-2-propyl imidazol- 5-carboxylic acid ethyl ester (50 gms) and powdered potassium hydroxide (25 gms). To this was charged 4-[2-(trityltetrazol-5-yl)phenyl]benzyl bromide (135 gms) at 45-500C. The contents were stirred for 5 hours at 45-500C. Diisopropylethyl amine (100 ml) was charged to the reaction mass at 40-45C. To this was slowly added a solution of 5-methyl-2-oxo- 1 ,3-dioxane-4-yl) methyl chloride (80 gms) diluted with dimethyl acetamide (160 ml) at 40- 45C over a period of 1 hour. The contents were heated to 60-650C and maintained for 4 hours. The reaction mass was then cooled to 30-350C. and was neutralized with concentrated hydrochloride acid. The reaction mass was filtered to remove inorganics. The reaction mass was charcoalized using charcoal (10 gms) and was stirred for 30 minutes at 40-450C. The reaction mass was filtered over hyflo. The clear filtrate was quenched with purified water(200 ml)at 25-30C over a period of 3-4 hours. The contents were stirred at 25-300C for 30 minutes. Crude trityl olmesartan medoxomil was isolated by filtration, slurried in water (500 ml), centrifuged and dried under reduced pressure at 45-50C.

The synthetic route of Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CIPLA LIMITED; CURTIS, Philip, Anthony; WO2008/43996; (2008); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem