Author: Jessica.F

3543-74-6, Adding some certain compound to certain chemical reactions, such as: 3543-74-6, name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, 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 3543-74-6.

Example 12 Synthesis of 4-[5-[bis(2-chloroethyl)amino]-1-methyl-1H-benzimidazol-2-yl]butanoic acid (9, Bendamustine) To a solution of compound (7) (5.00 g, 14 mmol) in 40 ml methylene chloride thionyl chloride (4.26 g, 36 mmol) is added at 5 C. Afterwards, the solution is stirred at ambient temperature for 16 h. The solvent is removed by distillation under vacuum. To the thereby produced brown oil 45 ml of 37% hydrochloric acid and 30 ml water is added and heated to 95 C. for 30 min. Subsequently 0.9 g activated carbon is added and stirred for 10 minutes at 95 C. The product is filtered and concentrated under vacuum until a dried product is formed. Afterwards a crystallisation of compound (9) is carried out in 20 ml water. The product was filtered, washed with water and acetone and dried under vacuum for 2 h at 50 C. The yield of compound (9) amounts to 4.3 g (11 mmol) with a content >99% (73% of theory).

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 3543-74-6.

Reference:
Patent; Heyl Chemisch-pharmazeutische Fabrik GmbH & Co. KG; Frey, Michael; Walther, Dirk-Detlef; US2014/31560; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 22884-10-2, name is 2-(1H-Imidazol-1-yl)acetic acid, molecular formula is C5H6N2O2, 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. 22884-10-2

Example 1; [0022] An oven-dried 250 ml_ 4-neck RB flask was fitted with a mechanic stirrer, K-thermocouple, condenser, nitrogen inlet and outlet and two 1/8 inch polytetrafluoroethylene (PTFE) feeding lines. The system was flushed with nitrogen for 30 minutes. Under nitrogen protection, imidazoIe-1-ylacetic acid (15.97 g, 0.13 mole), sulfolane (70 ml_) and phosphorous acid (2.67 g, 0.033 mol) were charged to the RB flask. The reaction mixture was mixed at 210 RPM and heated to 600C. PCI3 (9.18 g, 0.067mol) was added slowly (1.3 mL/mn) via a masterflex tubing pump. Five minutes were allowed for mixing. Alternately fed were 26 wt% phosphorous acid sulfolane solution (30.7 g, 10.23 g each addition at 1.6 mL/min) and PCI3 (27.5 g, 9.18 g each portion at 1.3 mL/min). Three to five minutes of mixing were allowed between additions. The addition took 1 hr 3 min and temperature was maintained between 600C and 670C. After addition was complete, the temperature of the reaction mixture was raised to 800C and was held at this temperature for 4 hours. Then the temperature of the reaction mixture was raised to 880C and held for 30 minutes. Ambient temperature water (50 g) was added in to quench the reaction. The solution was refluxed for 3 hrs . temperature, the product was vacuum-filtered and rinsed with 38 g of acetone. Zoledronic acid was obtained as a white crystalline solid (24.1 g, 95.3wt% purity by quantitative NMR, 65% yield). Example 2; [0023] An oven-dried 250 mL 4-neck RB flask was fitted with a mechanic stirrer, K-thermocouple, condenser, nitrogen inlet and outlet and two 1/8 inch PTFE feeding lines. The system was flushed with nitrogen for 30 minutes. Under nitrogen protection, imidazole-1-ylacetic acid (15.97 g, 0.13 mole), sulfolane (70 mL) and phosphorous acid (2.67 g, 0.033 mol) were charged to the RB flask. The reaction mixture was mixed at 300 RPM and heated to 600C. PCI3 (9.18 g, 0.067mol) was added in slowly (1.3 mL/min) via a masterflex tubing pump. Five minutes were allowed for mixing. Alternately fed were 26 wt% phosphorous acid sulfolane solution (30.7 g, 10.23 g each addition at 1.6 mL/min) and PCI3 (27.5 g, 9.18 g each portion at 1.3 mL/min. Three to five minutes of mixing were allowed between additions. The addition took 1 hr 6 min and temperature was maintained between 54 and 64C. After addition was complete, the temperature of the reaction mixture was raised to 800C and held for 4 hours. Then the temperature of the reaction mixture was raised to 880C and held for 30 minutes. This slurry was transferred via 3/8″ PTFE tubing using nitrogen pressure into 100 mL of pre-heated (80C) water under mixing. The resultant water solution was heated to refluxing and held at that temperature for 4 hr. It was then slowly cooled to room temperature then to 1-2C and held for 1.5 hr at this temperature. The product was collected via vacuum filtration. The cake was rinsed with acetone (20 g) and zoledronic acid was obtained as a white crystalline solid (19.1 g, 98.3 wt% purity by quantitative NMR, 53% yield). Example 3; [0024] An oven-dried 250 mL 4-neck RB flask was fitted with a mechanic stirrer, K-thermocouple, condenser, nitrogen inlet and outlet and two 1/8 inch PTFE feeding lines. The system was flushed with nitrogen for 30 minutes. Under nitrogen protection, imidazole-1-ylacetic acid (15.9 g, 0.13 mole), sulfolane (70 mL) and phosphorous acid (2.67 g, 0.033 mol) were charged to the RB flask. The reaction mixture was mixed and heated to 6O0C. PCI3 (36.7 g, 0.267 mol) and phosphorous acid (8.0 g, 0.098 mol) in – . mL/min respectively. Reaction temperature remained between 6O0C and 67C during feeding, After addition of PCI3 and phosphorous acid, the reaction slurry was heated to 800C and held at that temperature for 4 hours. This slurry was then transferred via 3/8″ PTFE tubing using nitrogen pressure into 50 m._ of pre-heated (8O0C) water under mixing. The resultant water solution was heated to refluxing and held at that temperature for 4 hr. It was then slowly cooled to 48-500C. Acetone (200 ml_) was added in slowly and then it was cooled to 1-2C and held for 2 hr at this temperature. The product was collected via vacuum filtration. The cake was rinsed with acetone (35 g) and zoledronic acid was obtained as a white crystalline solid (22.1 g, 98.6 wt% purity by quantitative NMR, 61 % yield). Example 4; [0025] A 2.5 L resin-kettle was fitted with a mechanic stirrer, K-thermocouple, condenser, nitrogen inlet and outlet, two 1/8 inch PTFE tubing as PCI3 and phosphorous acid sulfolane solution feeding lines. The system was dried under a stream of nitrogen. Under nitrogen, imidazoleacetic acid (79.92 g, 0.63 mol), phosphorous acid (13.90 g, 0.17 mol) and sulfolane (350 ml_) were added to the resin-kettle and mixed at 200 RPM. The mixture was heated to 62C then PCI3 (36.7 g, 0.267 mol) was added in slowly (1.3 mL/min) using a masterflex tubing pump. The slurry was mixed for 5 minutes. Phosphoro…

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 22884-10-2, its application will become more common.

Reference:
Patent; ALBEMARLE CORPORATION; WO2008/157050; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

The chemical industry reduces the impact on the environment during synthesis 641571-11-1, name is 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline, I believe this compound will play a more active role in future production and life. 641571-11-1

0 ~ 5 ,will3- (4-methyl-1H-1-imidazolyl) -5-trifluoromethylaniline(24.1 g, 0.1 mol),Di-tert-butyl dicarbonate (21.8 g, 0.1 mol)And 200 mL of dichloromethane were added to a three-necked reaction flask,Triethylamine (28.5 g, 0.15 mol) was added dropwise with stirring,After that,Heating up to 25 ~ 35 ,Reaction for 12 hours,TLC detection,To the raw material reaction completely.The solvent was removed under reduced pressure,The resulting residue was recrystallized from ethyl acetate to give a white solidN- [3- (4-methyl-1H-1-imidazolyl) -5-trifluoromethylbenzene] tert-butoxycarbonylamine (III)(Tert-butoxycarbonyl protected compound of formula II), 29.5 g,Yield 86.5%.

The chemical industry reduces the impact on the environment during synthesis 641571-11-1. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Suzhou Lixin Pharmaceutical Co., Ltd.; Xu Xuenong; Bao Zhijian; Su Jian; Xue Jia; Gu Xinyu; Huang Dongliang; Chen Wei; Wang Zhe; (6 pag.)CN107188887; (2017); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

46006-36-4, 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. 46006-36-4, name is 1H-Benzimidazole-7-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows.

(3-Methylbenzoimidazol-4-yl)-(l-methyl-lH-spiro[chromeno[4,3- c]pyrazole-4,4′-piperidine]-l’-yl)methanone [00562] Step 1: (lH-Benzo[d]imidazol-4-yl)(l-methyl-lH-spiro[chromeno[4,3- c]pyrazole-4,4′-piperidine]-l’-yl)methanone To a solution of l-methylspiro[chromeno[4,3-c]pyrazole-4,4′-piperidine] (211 mg, 0.830 mmol), lH-benzimidazole-4-carboxylic acid (134 mg, 0.830 mmol) and triethylamine (346 mu, 2.50 mmol) in dichloromethane (2 mL) was added HATU (314 mg, 0.830 mmol) in one portion and the mixture was stirred for 12 hours. The reaction mixture was treated with 1M NaOH (1 mL) for 10 minutes. Dichloromethane (5 mL) was added. The two layers were separated and the aqueous layer was extracted with dichloromethane (2 x 5 mL). The organic layers were combined, washed with brine, dried over MgSC^, filtered and evaporated to yield a residue that was purified on silica using a gradient of 0.5-30% MeOH in dichloromethane to yield (lH-benzo[d]imidazol-4-yl)(l -methyl- lH-spiro[chromeno[4,3-c]pyrazole-4,4′- piperidine]-l’-yl)methanone. ESI-MS m/z calc. 399.5, found 400.5 (M+l)+. Retention time: 1.12 minutes (4 min run).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; HADIDA-RUAH, Sara, Sabina; KALLEL, Edward, Adam; MILLER, Mark, Thomas; PONTILLO, Joseph; ANDERSON, Corey; NUMA, Mehdi; FRIEMAN, Bryan, A.; BEAR, Brian, Richard; ARUMUGAM, Vijayalaksmi; HILGRAF, Nicole; MCCARTNEY, Jason; GROOTENHUIS, Peter, Diederik Jan; JOHNSON, James, Philip; WO2011/140425; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

A common heterocyclic compound, 152628-03-0, name is 4-Methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylic acid, molecular formula is C12H14N2O2, 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. 152628-03-0.

Methyl-6-carboxybenzimidazole 5. 00 kg, methylene chloride 15. 00 kg A solution of 3. 28 kg of thionyl chloride was added dropwise under stirring at 25 C with stirring. Reaction 1 hour, spare

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; WEITE(Hunan)Pharmaceutical co.,ltd,; he, liang; Luo, Hui; Mo, Wei; (9 pag.)CN105237457; (2016); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1632-83-3, 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. 1632-83-3, name is 1-Methylbenzimidazole belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: To a flame-dried reaction tube was added 1,3-azoles (0.5 mmol, 1.0 eq), 1,10-phenoline (0.5 mmol, 1.0 eq), LiOtBu (1.0 mmol, 2.0 eq), CuBr2 (0.10 mmol, 0.2 eq) and iodine (0.75 mmol, 1.5 eq). Dry 1,4-dioxane (2 mL) was added to the mixture and the mixture was heated to 80C by putting the reaction tube to a preheated oil bath until the products were not increased. The mixture was cooled to room temperature and filtered through a short pad of silica gel. The silica gel was washed with EtOAc (20 mL) and the combined the organic phase was concentrated under reduced pressure to give a residue which was purified by silica gel column chromatography to afford the iodination product.

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

Reference:
Article; Zhao, Xia; Ding, Fang; Li, Jingyu; Lu, Kui; Lu, Xiaoyu; Wang, Bin; Yu, Peng; Tetrahedron Letters; vol. 56; 3; (2015); p. 511 – 513;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

2302-25-2, Adding a certain compound to certain chemical reactions, such as: 2302-25-2, name is 4-Bromo-1H-imidazole, 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 2302-25-2.

The 2-(4-bromo-lH-imidazol-l-yl)-5-(trifluoromethyl)pyridine was obtained as follows:A dried pressure tube was charged with 4-bromo-lH-imidazole (100 mg, 667 muiotaetaomicron), tetrahydrofuran (3 ml), N,N-dimethylformamide (2 ml), 2-(methylsulfonyl)-5- (trifluoromethyl)pyridine (150 mg, 667 muiotaetaomicron), and cesium carbonate (261 mg, 800 muiotaetaomicron). The tube was sealed and heated at 105 C for 16 hours. For the workup, the reaction mixture was evaporated at reduced pressure and the residue directly purified by chromatography on silica gel using a gradient of heptane/ethyl acetate = 100:0 to 60:30 as the eluent. The 2-(4-bromo-lH- imidazol-l-yl)-5-(trifluoromethyl)pyridine (167 mg, 86% yield) was obtained as a crystalline white solid. MS (ISP): m/z = 292.0 [M+H]+ and 294.2 [M+2+H]+.

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, 4-Bromo-1H-imidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; SIENA BIOTECH S.P.A.; NARQUIZIAN, Robert; WOLTERING, Thomas; WOSTL, Wolfgang; WO2012/136603; (2012); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

The chemical industry reduces the impact on the environment during synthesis 934-22-5, name is 6-Aminobenzimidazole, I believe this compound will play a more active role in future production and life. 934-22-5

2,3-Dibromo-5-ethoxy-6-hydroxybenzaldehyde (0.1 g, 0.31 mmol), 5-Aminobenzimidazole (0.03 g, 0.20 mmol), and isoamyl alcohol (2 mL) were stirred at room temperature under N2. Acetic acid (0.07 mL) was added drop-wise, and the mixture was refluxed overnight. The reaction mixture was filtered, washed with CH2Cl2, MeOH, and dried to yield 29 (0.06 g, 0.13 mmol, 65.4%) as an orange powder. 1H NMR (DMSO, 300 MHz) delta 15.57 (s, 1H), 12.50 (bs, 1H), 9.20 (s, 1H), 8.31 (s, 1H), 7.81-7.68 (m, 2H), 7.38 (s, 1H), 7.35 (s, 1H), 4.10 (q, 2H, J=6.9 Hz), 1.36 (t, 3H, J=6.9 Hz); 13C NMR (DMSO, 700 MHz) delta 162.36, 154.82, 148.63, 144.23, 140.92, 120.40, 119.77, 117.69, 117.42, 117.30, 116.15, 113.00, 111.88, 104.91, 65.01, 15.00. Rf=0.48 (CH2Cl2/MeOH 9:1)

The chemical industry reduces the impact on the environment during synthesis 934-22-5. I believe this compound will play a more active role in future production and life.

Reference:
Article; Shim, Hyun Jae; Yang, Hye Ran; Kim, Han Ie; Kang, Shin-Ae; No, Kyoung Tai; Jung, Young Hoon; Lee, Seung-Taek; Bioorganic and Medicinal Chemistry Letters; vol. 24; 19; (2014); p. 4659 – 4663;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

60-56-0, name is 1-Methyl-1H-imidazole-2(3H)-thione, 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. 60-56-0

2-chlorosulfonyl-1-methylimidazole Bleach (12% w/w aq, 110 ml) was cautiously added dropwise to a solution of 2-mercapto-1-methylimidazole (2.0 g) in conc. H2SO4 (50 ml) cooled to 0 C. After stirring 30 minutes at 0 C. the mixture was diluted with H2O (30 ml) and dichloromethane (30 ml). The aqueous layer was re-extracted with dichloromethane and the combined organic layers dried (MgSO4) and evaporated to give the product as an oil (730 mg).

Statistics shows that 60-56-0 is playing an increasingly important role. we look forward to future research findings about 1-Methyl-1H-imidazole-2(3H)-thione.

Reference:
Patent; Lewis, Huw David; Harrison, Timothy; Shearman, Mark Steven; US2009/215775; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

These common heterocyclic compound, 16042-25-4, name is 2-Imidazolecarboxylic acid, 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. 16042-25-4

To a suspension of 0.31 g of imidazole-2-carboxylic acid (2.76 mmol) in 14 ml DMF was added 0.448 g of CDI (2.76 mmol), 0.38 ml triethylamine (2.76 mmol) and stirred at ambient temperature for 1 h. Then the mixture was refluxed for 30 min. After cooling to ambient temperature, 0.5 g of 5-phenyl-o-anisidine (2.5 mmol) was added and the reaction mixture was heated to reflux for 16 h. The mixture was evaporated and the residue taken up in water (40 ml) and extracted 3 times with methylene chloride. The combined organic phases were tried on sodium carbonate, evaporated and the residue was stirred in hot ethyl acetate. After filtration and drying, 0.11 g 1H-imidazole-2-carboxylic acid (4-methoxy-biphenyl-3-yl)-amide (14%) were obtained as a light yellow solid; M.p.: 276 C. 0.1 g of 1H-Imidazole-2-carboxylic acid (4-methoxy-biphenyl-3-yl)-amide (0.36 mmol) was taken up in toluene (5.0 ml) and treated with 0.435 g of Lawesson reagent (1.0 mmol). The reaction mixture was heated to reflux for 16 h. After cooling to ambient temperature, water (25 ml) was added and the mixture was extracted 3 times with dichloro methane. The combined organic phases were dried on sodium carbonate, evaporated and the residue triturated in methanol. 0.08 g of 1H-imidazole-2-carbothioic acid (4-methoxy-biphenyl-3-yl)-amide (73%) were obtained as a yellow solid; M.p.: 223-226 C. [0204] 0.049 g of 1H-Imidazole-2-carbothioic acid (4-methoxy-biphenyl-3-yl)-amide (0.16 mmol) was taken up in chloroform and treated with 8.1 mul of Br2 (0.16 mmol) for 4 h at reflux. Then the reaction was quenched with sodium thiosulfate (38%) and extracted with chloroform. The combined organic phases were dried on sodium sulfate, filtered and evaporated. The residue was subjected to column chromatography (silica gel, methylene chloride/methanol 40:1) to yield 0.016 g of 2-(1H-imidazol-2-yl)-4-methoxy-7-phenyl-benzothiazole (33%) as a colorless solid; M.p.: 205-206 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 16042-25-4.

Reference:
Patent; Flohr, Alexander; Jakob-Roetne, Roland; Norcross, Roger David; Riemer, Claus; US2004/229862; (2004); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem