Month: January 2021

Reference of 641571-11-1, These common heterocyclic compound, 641571-11-1, name is 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline, 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.

General procedure: A mixture of acid 7b (or 7c) (1.3 equivalents), 1-hydroxybenzotriazole (1.3 equivalents), andN,N?-dicyclohexylcarbodiimide or 1,1?-carbonyldiimidazole (1.3 equivalents) was dissolved in dryDMF. Et3N (2.5 equivalents) and amine R2NH2 (one equivalent) were added. The resulting mixture was stirred at room temperature. The reaction progress was monitored by TLC. The solvent wasremoved under reduced pressure. The crude was diluted with water, and NH4OH was added to obtainpH = 10-11. The resulting solid was filtered and washed with water. The product was purified bycolumn chromatography on silica gel.

Statistics shows that 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline is playing an increasingly important role. we look forward to future research findings about 641571-11-1.

Reference:
Article; Kalinichenko, Elena; Faryna, Aliaksandr; Kondrateva, Viktoria; Vlasova, Alena; Shevchenko, Valentina; Melnik, Alla; Avdoshko, Olga; Belko, Alla; Molecules; vol. 24; 19; (2019);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 16042-25-4, name is 2-Imidazolecarboxylic acid, 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 16042-25-4, Computed Properties of C4H4N2O2

Step 1: To a solution of compound 1c (1 equivalent) in dichloromethane, compound 14a (1.5 eq.) was added sequentially.HOAT (1.5 eq.), HATU (2 eq.), DIPEA (6 eq.), stirred at room temperature for 12 hours.The solvent is then sparged off and directly isolated by column chromatography to afford intermediate 14b.

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

Reference:
Patent; Chinese Academy Of Sciences Shanghai Pharmaceutical Institute; Chinese Academy Of Sciences Shanghai Life Sciences Institute; Zhang Ao; Gao Daming; Ni Jiabin; Hu Hongli; Ding Chunyong; (55 pag.)CN107814792; (2018); A;,
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. 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, A new synthetic method of this compound is introduced below., Quality Control of 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

To BIT (130 g, 1 eq) was added acetone (650 mL, 5 vol) at 25C – 30C, and the mixture was dissolved. The reaction mixture was cooled to 0C – 5C, and a solution of potassium hydroxide (30.5 g, 3 eq) in desalting water (130 mL, 1 vol) was slowly added over 15 min. The reaction temperature was warmed to 40C – 45C, and the mixture was stirred at 40C – 45C for 5 hr. Using TLC (thin layer chromatography) (TLC eluent: 10% methanol/methylene chloride, detection method: UV), complete disappearance of BIT was confirmed. [0303] The precipitated solid was filtered, and the filtrate was concentrated under reduced pressure at 40C – 45C. To the obtained concentrated residue were added 25% brine (520 mL, 4 vol) and ethyl acetate (780 mL, 6 vol). After stirring for 10 min, the mixture was left standing for 5 min and partitioned. The aqueous layer was extracted with ethyl acetate (2×260 mL, 2×2 vol), and the extracts were combined with the organic layer. To the organic layer was added saturated aqueous sodium hydrogen carbonate (3×390 mL, 3×3 vol), and the mixture was stirred for 5 min, left standing and partitioned. To the organic layer was added saturated brine (650 mL, 5 vol), and the mixture was stirred for 5 min, left standing and partitioned. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure at 40C – 45C to give crude product of BIC (115 g, 87%) as a white solid. The crude product was directly used for the next step.

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; API Corporation; SEKI, Masahiko; EP2891650; (2015); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 32673-41-9, name is 4-Imidazolemethanol hydrochloride, 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 32673-41-9, HPLC of Formula: C4H7ClN2O

EXAMPLE 1 Ethyl 2-ethoxy-6-(4-(hydroxymethyl)imidazole-1-yl)-7-nitroquinoline-3-carboxylate To a solution of ethyl 2-ethoxy-6-fluoro-7-nitroquinoline-3-carboxylate (1.00 g, 3.24 mmol) in acetonitrile (10 ml) were added 4-(hydroxymethyl)imidazole hydrochloride (2.18 g, 16.2 mmol) and successively triethylamine (3 ml), and the mixture was stirred for 16 hours at 120 C. in a sealed tube under shading. After cooling, solvent was distilled off and the residue was submitted to silica gel column chromatography [dichloromethane-methanol(50:1?20:1)] under shading to obtain 583 mg of title compound as light brown powder. Yield 47%. 1H-NMR(DMSO-d6, delta): 1.35(3H,t,J=7.3 Hz), 1.42(3H,t,J=7.3 Hz), 4.38 (2H,q,J=7.3 Hz), 4.42(2H,d,J=6.8 Hz), 4.58(2H,d,J=7.3 Hz), 5.05(1H, t,J=5.4 Hz), 7.27(1H,s), 7.88(1H,s), 8.39(1H,s), 8.50(1H,s), 8.87 (1H,s).

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-Imidazolemethanol hydrochloride, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Kyorin Pharmaceutical Co., Ltd.; US6562839; (2003); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 75370-65-9, 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. 75370-65-9, name is 4-Amino-1H-benzo[d]imidazol-2(3H)-one, This compound has unique chemical properties. The synthetic route is as follows.

Amine 2af (1 g, 5.5 mmol) was dissolved in 20 ml of AcOEt and at 0C triphosgene (1.63 g, l equiv.) was added to the solution. The mixture was warmed at 80C for 4 hours then evaporated and the residue was dissolved in 10ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound la (820 mg, 5.5 mmol) and the mixture was warmed at 80C for 8 hours. (TLC AcOEt). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1 X 20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 550mg of a white solid. Yield = 28% ‘HNMR (DMSO, 200 MHz) delta 2.64 (6H, s), 4.34 (2H, d, J = 5.8 Hz), 6.62 (1H, dd, J = 7.2 Hz, J’ = 1 Hz), 6.73 (1H, t), 6.83 (1H, t, J = 7.6 Hz), 6.90 (1H, dd, J = 8.2 Hz, J’ = lHz), 7.06 (2H, m), 7.31 (1H, d, J = 8.8 Hz), 8.33 (1H, bs), 9.98 (1H, bs), 10.59 (1H, bs); [M+1] 360.7 (C17H18ClN5O2 requires 359.81).

The chemical industry reduces the impact on the environment during synthesis 4-Amino-1H-benzo[d]imidazol-2(3H)-one. I believe this compound will play a more active role in future production and life.

Reference:
Patent; PHARMESTE S.R.L.; NAPOLETANO, Mauro; TREVISANI, Marcello; PAVANI, Maria Giovanna; FRUTTAROLO, Francesca; WO2011/120604; (2011); 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 60-56-0 as follows. Recommanded Product: 1-Methyl-1H-imidazole-2(3H)-thione

General procedure: To a solution containing a thione (1, 6, 8, or 10, 1.0 equiv) in water (2.5 mL) and acetonitrile(1.5 mL) was added saturated aqueous ammonium hydroxide. After the solution was stirred atroom temperature for 30 min, a 3-(chloromethyl)coumarin (2, 1.5 equiv) was added and stirring wascontinued at room temperature for 15 min to 2.0 h. Acetonitrile therein was removed under reducedpressure and water was further removed under reduced pressure over P2O5 with a Kuegelrohr GKR-51apparatus (BUCHI, Flawil, Switzerland). The residue was purified by use of column chromatographypacked with silica gel to give the desired products with purity of >98.0%, as determined by HPLC(see Supplementary Materials).

According to the analysis of related databases, 60-56-0, the application of this compound in the production field has become more and more popular.

Reference:
Article; Tsay, Shwu-Chen; Lin, Shu-Yu; Huang, Wen-Chieh; Hsu, Ming-Hua; Hwang, Kuo Chu; Lin, Chun-Cheng; Horng, Jia-Cherng; Chen, I-Chia; Hwu, Jih Ru; Shieh, Fa-Kuen; Leyssen, Pieter; Neyts, Johan; Molecules; vol. 21; 2; (2016);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 36947-68-9, A common heterocyclic compound, 36947-68-9, name is 2-Isopropyl-1H-imidazole, molecular formula is C6H10N2, 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.

Reference Example 110: 2-Methyl-2-(3-nitro-phenyl)-propionic acid 2-(2- isopropyl-imidazol-l-yl)-ethyl esterTo a solution of 2-methyl-2-(3-nitro-phenyl)-propionic acid 2-bromo-ethyl ester (1.5_g, 4.74 mmol) in DMF (8 mL) was added sodium iodide (0.73 g, 4.87 mmol) and heated at 100 C for 1 h. 2-Isopropyl-imidazole (2.15 g, 19.5 mmol) and triethylamine (2 mL, 14.6 mmol) were added and then refluxed for 4 h. The reaction was diluted with water and extracted with DCM. The organic layer was-washed thoroughly with water, dried over sodium sulfate and evaporated to obtain crude compound. Purification by column chromatography on silica gel (60-120 mesh), eluting with 30% ethyl acetate/hexane gave 2-methyl-2-(3-nitro-phenyl)-propionic acid 2-(2-isopropyl- imidazol-l-yl)-ethyl ester (320 mg, 20%) as a solid.

The synthetic route of 36947-68-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F2G LTD; WO2008/62182; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 4857-06-1, 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. 4857-06-1, name is 2-Chloro-1H-benzo[d]imidazole, This compound has unique chemical properties. The synthetic route is as follows.

2-chloro- 1 -methyl- 1 H-benzo [d] imidazole[670] To a solution of 2-chloro- lH-benzo[d]imidazole (2.0 g, 13.1 mmol) in DMF(10 mL) was added NaH (0.63 g, 15.7 mmol) at 0 C under N2. After stirring for 30 min at 0 C, iodomethane (5.58 g, 39.3 mmol) was added and the mixture was stirred at room temperature for additional 1 hour. The reaction mixture was quenched with water (100 mL). The aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic layers were dried over a2S04, filtered, and concentrated to give the title compound (1.9 mg, 8.9 mmol, 67.9 % yield) as a white solid. MS: MS (M+H)+; XH NMR (400 MHz, CDC13): ? 7.71-7.68 (m, 1H), 7.31-7.27 (m, 3H), 3.79 (s, 3H).

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

Reference:
Patent; ABBVIE INC.; BAYBURT, Erol K.; CLAPHAM, Bruce; COX, Phil B.; DAANEN, Jerome F.; GOMTSYAN, Arthur; KORT, Michael E.; KYM, Philip R.; VOIGHT, Eric A.; SCHMIDT, Robert G.; DART, Michael J.; GFESSER, Gregory; WO2013/62966; (2013); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 4857-06-1,Some common heterocyclic compound, 4857-06-1, name is 2-Chloro-1H-benzo[d]imidazole, molecular formula is C7H5ClN2, 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.

[0700] 2-chloro-1H-benzo[d]imidazole (5 g, 32.8 mmol) was added to a solution of NAH (1.31 g, 32.8 mmol, 60%) in DMF(50 ml) below 10 C. After addition, the reaction mixture was stirred at 20 C for 2h. Then sem-c1 (5.46 g, 32.8 mmol,) was added to the reaction mixture. The reaction mixture was stirred at 20 C for 16hrs. Water (150 ml) and EtOAc (150 ml) were added. The organic layer was separated and washed by brine (100 ml), concentrated to give a residue. The crude product was purified by silica gel column (petroleum ether: ethyl acetate = 20: 1~ 4: 1) to give compound 264a (3.50 g, yield: 37.8%) as an oil. 1H NMR (400mhz, CDCl3) delta 7.78 – 7.71 (m, 1h), 7.54 – 7.48 (m, 1h), 7.41 – 7.32 (m, 2h), 5.62 (s, 2h), 3.66 -3.59 (m, 2h), 0.99 – 0.93 (m, 2h), 0.07 (d, j = 2.0 hz, 2h), 0.00 (s, 9h).

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-1H-benzo[d]imidazole, its application will become more common.

Reference:
Patent; BLADE THERAPEUTICS, INC.; BUCKMAN, Brad, Owen; YUAN, Shendong; ADLER, Marc; EMAYAN, Kumaraswamy; MA, Jingyuang; (687 pag.)WO2018/64119; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 50995-95-4,Some common heterocyclic compound, 50995-95-4, name is 2-Propylimidazole, molecular formula is C6H10N2, 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.

1(a) Ethyl-2-(2-propylimidazol-1-yl)propanoate 2-Propylimidazole (5.5 g), ethyl 2-bromopropionate (9.95 g) and potassium carbonate (12.4 g) were stirred in refluxing acetonitrile (100 ml) for 72 hours. The suspension was allowed to cool, filtered and the solvent removed under reduced pressure, yielding the title compound as an off-white foam, 9.2 g [88%].

The synthetic route of 50995-95-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Pfizer Inc.; US4853392; (1989); A;; ; Patent; Pfizer Limited; EP299727; (1991); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem