Author: Jessica.F

Application of 84946-20-3, 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.

EXAMPLE 43 Norastemizole. To a 25 mL 3-neck flask equipped with a thermometer, ref lux consenser and stir bar were added, under a nitrogen atmosphere, 822 mg (4.8 mmol) of Compound XVI, obtained according to the procedure of Example 6, and 0.93 mL (8.0 mmol) of lutidine. The mixture was heated to 120 C., whereupon a solution of 1.04 g (4 mmol., 1 eq.) of Compound X (Aldrich Chemical Co., Milwaukee, Wis.), 8 mmol of tetrabutylammonium fluoride (obtained from its 1.0M THF solution by distillation under vacuum with anhydrous toluene) and 4 mL of N-methylpyrrolidinone was added slowly over 2 h. The reaction mixture was allowed to stir at 120 C. for 2 h. High-performance liquid chromatography revealed >95% coversion to Compound XVIII. The reaction mixture was allowed to cool to ambient temperature, and slowly poured into a solution of 5% aqueous NaOH while stirring. The resulting suspension was allowed to stir at 0-10 C. for 30 minutes, and the resulting solid product was collected by vacuum filtration, washed with water (3*5 mL), and air dried for 30 minutes under vacuum to afford a crude mixture of Compound XVIII and 6% (HPLC) of migration product Compound XIX. NMR data for Compound XVIII: 1 H NMR (300 MHz, DMSO-d6) delta7.30-7.02 (6H, m two groups), 6.95 (1H, pseudo t, J=7.8, 2.3 Hz), 6.85 (1H, pseudo t, J=7.8, 2.3 Hz), 5.35 (2H, s), 4.33 (1H, pseudo d), 4.02 (1H, m), 3.83 (1H, pseudo d), 3.17 (1H, pseudo t), 2.75 (1H, pseudo t), 2.02 (3H, s), 2.0 (2H, m overlapped), 1.45 (2H, m); 13 C NMR (75 MHz, DMSO-d6) delta168.0, 163.0 and 159.7 (13 C-19 F coupling), 153.9, 142.8, 134.3, 133.5, 129.1, 129.0, 128.2, 120.5, 118.4, 115.5, 115.2, 107.9, 44.8, 43.7, 32.3, 31.5, 21.4. It is to be noted that under the same reaction conditions as above, but without the use of tetrabutylammonium fluoride, only 4.9% conversion (high-performance liquid chromatography) to Compound XVIII was achieved after 3 h at 120 C. In addition, without the use of tetrabutylammonium fluoride, the ratio of Compound XVIII:Compound XIX was 4:1. The mixture of Compound XVIII obtained above was placed in a 50 mL, 3-neck flask equipped with a thermometer, reflux condenser and stir bar. 5 mL of 6N hydrochloric were added, and the resulting mixture was heated to 110 C. and allowed to stir at that temperature for 5 h. After the reaction was complete (>98% conversion to norastemizole as shown by high-performance liquid chromatography), the reaction mixture was allowed to cool to room temperature, and 10 mL of toluene and 10 mL of water were added, with stirring.

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; Sepracor Inc.; US5817823; (1998); A;,
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 38993-84-9 as follows. Application In Synthesis of (1-Methyl-1H-imidazol-5-yl)methanol

To the solution of (1 -methyl- lH-imidazol-5-yl)methanol (570 mg, 5 mmol) in dioxane (50 niL) in a 250 mL round bottom flask, was added NCS (815 mg, 6 mmol). The resulting mixture was stirred at room temperature overnight. Dioxane was removed under vacuum.

According to the analysis of related databases, 38993-84-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CHLORION PHARMA, INC.; UNIVERSITE LAVAL; ATTARDO, Giorgio; TRIPATHY, Sasmita; WO2010/132999; (2010); 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 4857-06-1 as follows. Application In Synthesis of 2-Chloro-1H-benzo[d]imidazole

Example 1N-(4-Fluoro-3-trifluoromethyl-benzyl)-N-(1-methyl-1H-benzimidazol-2-yl)-benzenesulfonamide (Compound No.15)Step A: 2-Chloro-1-methyl-1H-benzimidazoleTo a solution of 2-chloro-1H-benzimidazole (5.03 g, 33.0 mmol) in anhydrous DMF (33 mL) at 0 C. was added portion-wise 95% NaH (871 mg, 36.3 mmol). The ice bath was removed and the resulting mixture was stirred at room temperature for 1 h. Iodomethane (4.68 g, 33.0 mmol) was added and the resulting mixture was stirred at room temperature overnight. The resulting mixture was then diluted with water, and the resulting precipitate was collected by filtration and purified by recrystallization from hexane to yield 2-chloro-1-methyl-1H-benzimidazole. MS 167 (M+1)+

According to the analysis of related databases, 4857-06-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Jetter, Michele C.; Macielag, Mark J.; Xia, Mingde; Xu, Xiaoqing; US2011/3801; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 41716-18-1, 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. 41716-18-1, name is 1-Methyl-1H-imidazole-4-carboxylic acid belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a suspension of [1-METHYL-IMIDAZOLE-4-CARBOXYLIC ACID (11.] 4g, 90 [MMOL)] in THF (500ml) at [0°C,] was added drop-wise a solution of lithium aluminium hydride [(1 M] in THF, [117ML,] 117 [MMOL)] and the mixture was stirred at room temperature overnight and then at [50°C] for 1 hour Water (3 [ML)] was added followed by [NA2SO4] and the mixture was filtered through [CELITETM.] The filtrate was concentrated under reduced pressure to afford the title compound as a solid [(8G,] 78.95percent) ;’H NMR (300 MHz, [CDCI3)] 6 ppm: 7.25 (s, 1 H), 6. 7 (s, 1H), 5.25 (m, 1H), 4.4 (s, 2H), 3.45 (s, 3H).

The synthetic route of 1-Methyl-1H-imidazole-4-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2004/13138; (2004); A2;,
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.

Sodium hydride (purity 55%)(516 mg, 12.0 mmol) was added to a N,N-dimethylformamide solution (8.0 ml) of 2-chloro-1H-benzimidazole (1.52 g, 10.0 mmol), at 0C, under nitrogen stream, and stirring was carried out for 20 minutes. Methyl iodide (0.750 ml, 12.0 mmol) was further added, and stirring was carried out under room temperature for 2 hours. Water was added to the reaction solution, and the resulting solid substance was collected by filtration to afford 2-chloro-1-methyl-1H-benzimidazole (1.51 g, yield 91%) as a white solid.

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; Daiichi Sankyo Company, Limited; EP2258697; (2010); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. 540516-28-7, name is 2-(Hydroxymethyl)-5-bromobenzimidazole belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 2-(Hydroxymethyl)-5-bromobenzimidazole

Synthesis of 5-bromo-1H-benzimidazole-2-carboxylic acid hydrochloride 44 was prepared using 5-bromo-1H-benzimidazole-2-yl)-methanol 28 (0.23 g, 1.0 mmol) dissolved in acetone (10 mL) and potassium permanganate (0379, 2.4 mmol) dissolve in water (10 mL). The crude product was recrystallised from water. 5-Bromo-1H-benzimidazole-2-carboxylic acid in Yield 37% was recovered as a creamy white powder.

The synthetic route of 540516-28-7 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Alasmary, Fatmah A.S.; Snelling, Anna M.; Zain, Mohammed E.; Alafeefy, Ahmed M.; Awaad, Amani S.; Karodia, Nazira; Molecules; vol. 20; 8; (2015); p. 15206 – 15223;,
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. 2963-77-1, name is 4-(1H-Benzo[d]imidazol-2-yl)aniline, This compound has unique chemical properties. The synthetic route is as follows., name: 4-(1H-Benzo[d]imidazol-2-yl)aniline

Example 37: Preparation OF 2-BENZO L, 3] DIOXOL-5-VL-N- [3- (LH-BENZIMIDAZOL-2-YL)- PHENYLL-ACETAMIDE (Compound M To a 5.0 ml methylene chloride solution of (3,4-methylene-dioxy) phenyl acetic acid (182. 9 mg, 1.0 mmol) was added methylene chloride oxalyl chloride solution (2 M, 0.60 ml, 1.2 mmol). Five drops of DMF was added with stirring at ambient temperature. Methylene chloride and other volatile materials were removed by reduced pressure after it was stirred at ambient temperature for 3.0 h. To the residue was added DMAP (10 MG), 4-(1H-benzimidazol-2-yl)-phenylamine (83 mg, 0.40 mmol) and pyridine (2.0 ml). The mixture was stirred at 60 C for 20 hrs. Water (20 ml) was added. The solid formed was collected and was washed with aq. NAOH (3 N, 2x 10 ml), water (10 ml), aq. HCl (2 N, 3 x 10 ml), water (2 x 5 ml), ether (2 x 5 ml). An off-white compound (12 mg, 8%) was obtained. MS M/Z = 372.05 (M+H) ; IH NMR delta 10.56 (s, 1 H), 8.15 (d, J=8. 7 Hz, 2 H), 7. 87 (d, J=8. 7 Hz, 2 H), 7.72 (m, 3 H), 7.42 (m, 2 H), 6.94-6. 80 (m, 3 H), 6.00 (s, 2 H), 3.63 (s, 2H).

According to the analysis of related databases, 2963-77-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; IMCLONE SYSTEMS INCORPORATED; WO2005/30206; (2005); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 104619-51-4, 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. 104619-51-4 name is Di(1H-imidazol-1-yl)methanimine, 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.

An oven dried round bottom flask was charged withdi(IH-imidazol-l-yl)methanimine (500 mg, 3.10 mmol),2-aminophenol (188 mg, 1.724 mmol) and anhydrous THF(20 ml) at room temperature. The resulting suspension wasrefluxed under N2 for 2 hr to give complete conversion basedon LC/MS. The solvent was removed in vacuo and the residuewas purified on a Biotage Flash Collector, eluting with30-80% EtOAc/Hexane (1200 ml) to afford the expectedproduct, benzo[d]oxazol-2-amine (200 mg, 1.5 mmol, 87%yield), as a white solid

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Di(1H-imidazol-1-yl)methanimine, and friends who are interested can also refer to it.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; COOK II, JAMES H; MCDONALD, IVAR M; KING, DALTON; OLSON, RICHARD E; WANG, NENGHUI; IWUAGWU, CHRISTIANA I; ZUSI, F.CHRISTOPHER; MACOR, JOHN E; (330 pag.)JP5714745; (2015); B2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 5805-57-2, name is (1H-Benzo[d]imidazol-2-yl)methanamine, 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 5805-57-2, Safety of (1H-Benzo[d]imidazol-2-yl)methanamine

To a stirred solution of (S)-methyl 2~amino-3~(2,4~ dichiorophenylipropanoate (103 mg, 0.415 mmol) in DCM (10 mL) was added DIPEA ( 1.5 equiv) and cooled to 0 C. A solution of triphosgene (0.33 equiv) in DCM (2 mL) was added dropwise to the reaction mixture and stirred at room temperature for 2 h. The solution was 106 back to 0 C and ( lH-benzo[d]imidazol-2-yl)niethanamine (1.5 equiv) in DCM (2 nil) was added. The reaction mixture was stirred at 0 C for 30niin. The solution washed with brine, dried over anhydrous sodium sulfate and evaporated under vacuum. The residue was purified by flash column chromatography to give (S)-methyi 2-(3-(( lH-benzo[dJimidazol-2- yl)methyl)ureido)-3-(2,4-dich{orophenyl)propanoate.

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, (1H-Benzo[d]imidazol-2-yl)methanamine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; UNIVERSITY OF WASHINGTON; BUCKNER, Frederick, S.; ALVAREZ, Ximena, Barros; FAN, Erkang; GILLESPIE, John, Robert; HOL, Wilhelmus, G.J.; HUANG, Wenlin; KOH, Cho, Yeow; RANADE, Ranae, M.; SHIBATA, Sayaka; VERLINDE, Christophe, L.M.; ZHANG, Zhongsheng; (249 pag.)WO2016/29146; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 641571-11-1, A common heterocyclic compound, 641571-11-1, name is 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline, molecular formula is C11H10F3N3, 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 solution of potassium t-butoxide (11 mL of 1M solution, 5.5 equiv.) in THF was slowly (10 min) added to compound 3b (0.77 g, 2.0 mmol) and 1-(3-amino-5-trifluoromethylphenyl)-4-methyl-1Himidazole (0.45 g, 2.0 mmol) dissolved in THF (30 mL) at -15 to -10 C under an argon atmosphere. The dark red solution was stirred at room temperature for 3.5 h and then cooled to 0 C and treated with saturated NaCl aqueous solution (25 mL). The organic layer was separated; the aqueous one was extracted with EtOAc (2×15 mL). Combined organic extracts were dried (Na2SO4) and evaporated. The yellow solid residue was treated with toluene (5-10 mL) and filtered off to obtain nilotinib trifluoromethyl derivative 7 (0.8 g, 67%) as yellow solid; m.p. 269-271 C (EtOH); 1H NMR: delta 2.14 (3H, s, CH3), 2.32 (3H, s, CH3), 7.44 (1H, s, 5-H imidazole), 7.46 (1H, d, J = 8.1 Hz, 5-H), 7.50 (1H, dd, J = 8.0, 4.8 Hz, 5-H Py), 7.69 (1H, s, 2-H imidazole), 7.79 (1H, dd, J = 8.1, 1.7 Hz, 6-H), 7.88 (1H, s, Pm), 8.11 (1H, s, 2-H Ar), 8.16 (1H, d, J= 1.7 Hz, 2-H), 8.20 (1H, s) and 8.25 (1H, s) 4,6-H Ar, 8.48 (1H, dt, J= 8.0, 1.7 Hz, 4-H Py), 8.68 (1H, dd, J= 4.8, 1.7 Hz, 6-H Py), 9.29 (1H, d, J= 1.7 Hz, 2-H Py), 9.83 (1H, s, NH), 10.57 (1H, s, NH). 13C NMR: delta 13.5 (CH3), 18.2 (CH3), 103.2 (q, J= 3 Hz, C-5 Pm), 111.6 (q, J= 4 Hz, C-6 Ar), 114.2, 114.3 (q, J= 4 Hz, C-4 Ar), 115.0 (C-2 Ar), 120.7 (q, J= 274 Hz, CF3), 123.6 (q, J= 271 Hz, CF3), 123.8 (C-5 Py), 124.5, 124.8, 130.7, 130.8 (q, J= 32 Hz, C-CF3), 131.2, 131.9, 134.8 and 134.9 (C-4 Py, C-3), 137.3, 137.7, 137.9, 138.9, 141.3, 148.5 (C-6 Py), 152.2 (C-2 Py), 156.5 (q, J= 35 Hz, C-CF3Pm), 161.1 (C-4 Pm), 165.1 (C=O), 165.4 (C-2 Pm). Anal. calcd for C29H21N7F6O: C, 58.29; H, 3.54; N, 16.41; found: C, 58.30; H, 3.65; N, 16.22%.

The synthetic route of 641571-11-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Terentjeva; Muceniece; Lusis; Journal of Chemical Research; vol. 39; 4; (2015); p. 223 – 225;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem