Author: Jessica.F

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 152628-03-0 as follows. category: imidazoles-derivatives

Stirring blade, a thermometer, three-neck flask 1L fitted with condenser, 4-methyl–2-n-propyl -1H- benzimidazole-6-carboxylic acid 50.0g (229mmol) and polyphosphoric acid added and stirred and 300 g, heated to around 70 C., the reaction solution obtained was stirred for 30 minutes, added in portions over a period N- methyl -O- phenylenediamine 45.0g of (368mmol) 2 hours It was.After adding the entire amount, stirring for 1 hour at around 70 C., and stirred for 5 h warmed to near yet 130. C..After confirming the disappearance of 4-methyl–2-n-propyl -1H- benzimidazole-6-carboxylic acid by HPLC, was cooled to about 70 C., while maintaining the water 600g The temperature of the reaction solution at 70 to 85 C. It was dropped little by little.After the total amount dropwise, 30 C. and cooled to near, pH of the reaction solution with aqueous ammonia was adjusted to be pH 8.3, after stirring for 1 hour warmed to around 50 C., the solid by vacuum filtration It is filtered off and washed the solid was filtered off with water 200g in the vicinity of 50 , to obtain a wet product of light brown crystals.Stirring blade, a thermometer, three-neck flask 1L fitted with condenser, was added and stirred the wet product of the resulting pale brown crystals and water 900 g, after stirring for 1 hour warmed to around 50 C. , vacuum filtered off the solids by filtration, wash the solid was filtered off with 100g of water around 50 C., the resulting wet product was dried for 15 hours under reduced pressure, a pale crude benzimidazole body as brown crystals to obtain a body 60.3g.The crude product of the benzimidazole body was analyzed by HPLC, the purity was 98.20%, the content of methyl benzimidazole body 0.14%, the content of ethyl benzimidazole body with 0.07% there were. stirring blade, a thermometer, three-necked flask 100mL fitted with a condenser, a mixture of a crude product 5.0g of methanol 12g and water 50g benzimidazole body obtained in Production Example 1 was added after stirring on, the addition of hydrochloric acid 2.1g containing hydrogen chloride 0.78 g (21.4 mmol), stirred for 10 minutes at about 25 C., the solid in the reaction solution was confirmed to be dissolved.Then, was added aqueous ammonia 1.1g containing ammonia 0.28 g (16.5 mmol), precipitation of white crystals was confirmed.After stirring for 1 hour at about 25 C., vacuum filtered through the solid was filtered off, the solid was filtered off with water 5g were washed twice and dried for 12 hours at 60 C. under reduced pressure and the resulting wet biomass, to obtain a benzimidazole body 4.2g (13.9mmol) as white crystals.Recovery rate, which is calculated based on the mass of the crude product of the benzimidazole body was 84.4%.As a result of the benzimidazole body obtained was analyzed by HPLC, the purity was 99.56%, the content of methyl benzimidazole body 0.06%, the content of ethyl benzimidazole body 0.02% met.

According to the analysis of related databases, 152628-03-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; TOKUYAMA CORPORATION; MIYAOKU, TAKAYUKI; (16 pag.)JP2015/160810; (2015); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 7189-69-7, name is 1,1′-Sulfonyldiimidazole, 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 7189-69-7, name: 1,1′-Sulfonyldiimidazole

NaH (60% in oil, 0.070g, 1.76mmol) was added to a stirred solution of compound 13 (0.23g, 0.16mmol) in dry DMF (3.5mL) at room temperature. After 1h, the suspension was cooled at -40C and 1,1?-sulfonyl-diimidazole (0.22g, 1.12mmol) in dry DMF (1.5mL) was added. After 24h the reaction mixture was quenched with MeOH and allowed to warm to room temperature, then diluted with water (40mL). The mixture was extracted with AcOEt (3×50mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated. Flash chromatography (hexane/AcOEt, 7:3) of the crude product gave trisaccharide 14 (0.21g, 85%) as an amorphous solid. [alpha]D20=+1.8 (c=1 in chloroform). 1H NMR (CDCl3): delta=7.94 (br s, 1H, Im), 7.53-7.10 (m, 45H, arom), 7.00 (m, 2H, Im), 5.46 (s, 1H, PhCH), 5.25-5.12 (m, 3H, H-1? and CH2Ph), 4.97 (d, 1H, J=11.1Hz, CH2Ph), 4.85-4.58 (m, 10H, H-1 and CH2Ph), 4.58-4.44 (m, 4H, H-2? and CH2Ph), 4.32 (d, 1H, J1?,2?=7.9Hz, H-1?), 4.23 (dd, 1H, J5?,6?=4.9Hz, J6a?,6b?=10.6Hz, H-6a?), 4.16-4.09 (m, 1H, CH2Ph), 4.09-3.80 (m, 5H, H-2, 3, 3?, 4?, 5?), 3.75-3.52 (m, 5H, H-a, 4, 5, 2?,4?), 3.52-3.20 (m, 7H, H-a?, c, c?, 6a?, 6b?, 3?, 6b?), 3.10-2.98 (m, 1H, H-5?), 1.91-1.69 (m, 2H, 2H-b), 1.29-1.21 (br d, 3H, 3H-6). 13C NMR (CDCl3): delta=155.6 (C=O), 139.1-136.5 (9C, arom), 136.8 (C Im),129.2-126.0 (46C, arom.), 118.6 (C Im), 101.4 (CHPh), 98.6 (C-1?), 98.2 (C-1), 97.1 (br s, C-1?), 85.7 (C-2?), 81.9 (C-4?), 80.3 (br s, C-4), 79.5 (C-3?), 79.2 (C-2?), 78.4 (br s, C-3), 76.7 (C-3?), 76.5 (br s, C-2), 76.2 (C-4?), 75.2 (2C, CH2Ph), 74.6 (br s, CH2Ph), 74.3 (CH2Ph), 73.6 (CH2Ph), 73.1 (br s, CH2Ph), 70.2 (C-5?), 68.4 (C-6?), 68.3 (C-5), 67.3 (C-6?), 67.2 (CH2Ph), 65.7 (C-5?), 65.2 (C-a), 50.8 and 50.5 (NCH2Ph), 44.6 and 43.7 (C-c), 28.4 and 27.9 (C-b), 18.0 (C-6). MS (ESI) m/z (%): 1550.3 (100) [M+NaM+Na]+. HRMS (ESI): m/z calcd for C88H93N3O19NaS 1550.6022 [M+Na]+, found 1550.6055

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, 1,1′-Sulfonyldiimidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Morelli, Laura; Fallarini, Silvia; Lombardi, Grazia; Colombo, Cinzia; Lay, Luigi; Compostella, Federica; Bioorganic and Medicinal Chemistry; vol. 26; 21; (2018); p. 5682 – 5690;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 360-97-4,Some common heterocyclic compound, 360-97-4, name is 4-Amino-1H-imidazole-5-carboxamide, molecular formula is C4H6N4O, 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 mixture of 0.252 g 5-amino-1H-imidazole-4-carboxamide(Acros Organics, 2 mmol) and 0.874 g 5Cl-STB(2 mmol) in 10 cm3 MeOH was heated to reflux for 3 h.The reaction mixture was left at room temperature (24 h)and filtered. The formed solid was crystallized from 5 cm3MeOH to give 0.47 g (80 %) brown crystals of 3d. M.p.:[410 C; 1H NMR (500 MHz, DMSO-d6): d = 13.49 (s,broad, 2H, NH, C(20)-OH), 10.45 (s, 1H, C(40)-OH), 8.34(s, 1H, C(2)-H), 7.54 (s, 1H, C(60)-H), 6.66 (s, 1H, C(30)-H) ppm; 13C NMR (125 MHz, DMSO-d6): d = 165.0,157.5, 154.7, 134.8, 133.4, 130.3, 128.8, 120.5, 117.4,111.7, 103.4 ppm; MS (70 eV): m/z (%) = 295 (M?, 100),261 (14), 260 (15), 235 (13), 187 (19), 165 (7), 171 (14),153 (7), 69 (7).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Amino-1H-imidazole-5-carboxamide, its application will become more common.

Reference:
Article; Matysiak, Joanna; Skrzypek, Alicja; Niewiadomy, Andrzej; Juszczak, Malgorzata; Langner, Ewa; Lemieszek, Marta; Rzeski, Wojciech; Karpiska, Monika M.; Walczak, Katarzyna; Monatshefte fur Chemie; vol. 146; 8; (2015); p. 1315 – 1327;,
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 104619-51-4 as follows. Recommanded Product: Di(1H-imidazol-1-yl)methanimine

Di(imidazole-1-yl)methanimine (10.49 mmol, 1.69 g) was added to a solution of 2-amino-5-chlorophenol (3.50 mmol, 0.50 g) in acetonitrile (50 mL) with constant magnetic stirring. The reaction was then placed under argon atmosphere and gently refluxed for eight hours. The reaction was then concentrated under reduced pressure and silica gel column chromatography (3:1 hexanes/ethyl acetate) provided a crystalline white solid in an 86% yield.

According to the analysis of related databases, 104619-51-4, the application of this compound in the production field has become more and more popular.

Reference:
Article; Rynearson, Kevin D.; Charrette, Brian; Gabriel, Christopher; Moreno, Jesus; Boerneke, Mark A.; Dibrov, Sergey M.; Hermann, Thomas; Bioorganic and Medicinal Chemistry Letters; vol. 24; 15; (2014); p. 3521 – 3525;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 147403-65-4, name is Methyl 2-ethoxy-1-((2′-(N-hydroxycarbamimidoyl)-[1,1′-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate, molecular formula is C25H24N4O4, 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. Formula: C25H24N4O4

10.0 g (22.5 mmol) of Intermediate II was added to 100 ml of 1,4-dioxane, heated to reflux,A solution of 3.84 g (23.7 mmol, 1.05 eq) of carbonyldiimidazole in 50 ml of 1,4-dioxane was slowly added dropwise,After completion of the dropwise addition, the reaction was refluxed for 5 hours; the reaction was stopped and the solvent was distilled off under reduced pressure;The residue was dissolved in ethyl acetate and added with water. Under stirring, HCl was adjusted to pH 3, allowed to stand for delamination,The aqueous phase was removed; water was added for washing, the aqueous phase was separated off and the organic phase was washed with saturated brine,The aqueous phase was removed and the organic phase was cooled with an ice-water bath to cool and crystallize for 1 hour, filtered, washed with a small amount of ethyl acetate,Impurity A was obtained in a yield of 85%

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 147403-65-4, its application will become more common.

Reference:
Patent; Shandong Xinhua Pharmaceutical Co., Ltd.; Wu Hui; Zheng Zhonghui; Wang Jun; Shen Hong; Xu Ling; (6 pag.)CN105924400; (2016); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 312-73-2, A common heterocyclic compound, 312-73-2, name is 2-(Trifluoromethyl)-1H-benzo[d]imidazole, molecular formula is C8H5F3N2, 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: To a methanolic solution (5 mL) of complex 1 (0.5 g, 1.259 mmol) was added dropwise methanolic solution (5 mL) of phen (0.250 g, 1.26 mmol) and the reaction mixture was refluxed at 60 C for 5 h. The reaction mixture yielded a solid product (green coloured) which was isolated, washed with diethyl ether and methanol in portion and dried in vacuum.

The synthetic route of 312-73-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Tabassum, Sartaj; Amir, Samira; Arjmand, Farukh; Pettinari, Claudio; Marchetti, Fabio; Masciocchi, Norberto; Lupidi, Giulio; Pettinari, Riccardo; European Journal of Medicinal Chemistry; vol. 60; (2013); p. 216 – 232;,
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. 1615-14-1, name is 2-(1H-Imidazol-1-yl)ethanol, This compound has unique chemical properties. The synthetic route is as follows., name: 2-(1H-Imidazol-1-yl)ethanol

106-1) 2-(1H-Imidazol-1-yl)ethyl p-tosylate 0.24 g(2.41 mmol) of 2-(1H-imidazol-1-yl)ethanol and 0.55 g(2.88 mmol) of tosylchloride were dissolved in 20 ml of dichloromethane, 0.67 ml of triethylamine was slowly added thereto at 0 C., and the mixture was stirred at room temperature for 4 hours. The organic solvent was removed under reduced pressure. The residue was dissolved in 10 ml of ethyl acetate, washed sequencially with 1N hydrochloric acid solution, saturated sodium bicarbonate solution and aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated. The residue was subjected to column chromatography(eluent: dichloromethane/methanol=20/1, v/v) to give 0.30 g(1.13 mmol, Yield 47%) of the title compound. 1H NMR(CDCl3) delta2.42(s, 3H), 4.17-4.28(m, 4H), 6.88(s, 1H), 6.99(s, 1H), 7.29(d, 2H), 7.45(s, 1H), 7.64(d, 2H)

According to the analysis of related databases, 1615-14-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; LG Chemical Ltd.; US6268363; (2001); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route 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.

General procedure: A mixture of 1d (1.0 eq.) and ethanolamine (10 eq.) was heated to 150 C for 30 min by use of microwave irradiation. After the reaction was completed, the reaction mixture was cooled down to room temperature. The precipitated solid was filtered and washed with diethyl ether. The crude product was purified by flash column chromatography (MeOH/methylene chloride) to give desired product 1e.

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:
Article; Oh, Sangmi; Kim, Sungbum; Kong, Sunju; Yang, Gyongseon; Lee, Nakyung; Han, Dawoon; Goo, Junghyun; Siqueira-Neto, Jair L.; Freitas-Junior, Lucio H.; Song, Rita; European Journal of Medicinal Chemistry; vol. 84; (2014); p. 395 – 403;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 930-62-1, 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 930-62-1 as follows.

Intermediate 27: 2,4-Dimethyl-1-trityl-1H-imidazole; A solution of trityl chloride (15 g, 55 mmol) in dichloromethane (50 mL) was added drop wise over 45 minutes to a solution of 2,4-dimethyl imidazole (5 g, 52 mmol) in a mixture of dichloromethane (100 mL) and triethylamine (11.3 mL, 81 mmol) at room temperature. The mixture was stirred over night, then quenched with methanol (4 mL) and stirred for additional 30 minutes. The solvent was evaporated, the residue taken up in toluene (600 mL), washed with potassium phosphate buffer (pH 7, 1M, 2x 200 mL) and with water (200 mL). The organic phase was diluted with dichloromethane (200 mL), dried over sodium sulfate, and concentrated under reduced pressure to -100 mL. Hexanes (100 mL) were added and the precipitated was collected by filtration and washed with hexanes (2x 50 mL) to give 14.76 g (84 %) of the product as a colourless solid. ¹H-NMR (CDCl3) 5: 1.62 (s, 3H); 2.16 (s, 3H); 6.40 (s, 2H); 7.10-7.40 (m, 15H).

According to the analysis of related databases, 930-62-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/116022; (2005); 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. 1072-62-4, name is 2-Ethyl-1H-imidazole, A new synthetic method of this compound is introduced below., Formula: C5H8N2

(a) 3-[3-(2-Ethylimidazol-l-ylmethyl)phenyl]-5-z^o-butyl-7V-fe7Y-butylthiophene- 2-sulfonamide; To a solution of 3-(3-bromomethylphenyl)-5-ziO-butyl-7V-fe7t-butylthiophene-2- sulfonamide (70 mg, 0.158 mmol; see Example l(e)) in dioxane (2.0 mL) was added 2-ethylimidazole (45.4 mg, 0.473 mmol) and the reaction mixture was stirred for 1 h at 80C. The reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography using MeOH:CH2Cl2 (6:94) as EPO eluent to give the sub-title compound in 85% yield as a colourless syrup (61.2 mg, 0.134 mmol).1H NMR delta (CDCl3): 0.95(s, 9H)5 0.96 (d, J= 6.5 Hz5 6H), 1.29 (t, J= 7.3 Hz5 3H)5 1.80-1.98(m, IH), 2.58-2.72 (m, 4H)5 4.11 (br s, IH)5 5.08 (s, 2H)5 6.70 (s, IH), 6.88 (s5 IH)5 6.98 (s, IH)5 7.08 (d, J – 7.7 Hz5 IH)5 7.39 (apparent t, J = 7.7Hz, IH)5 7.42 (s5 IH)5 7.51 (d, J= 7.7 Hz5 IH).13C NMR delta (CDCl3): 11.9, 20.2, 22.1, 29.4, 30.5, 39.1, 49.1, 54.5, 119.6, 126.7, 127.5, 127.7, 128.5, 128.7, 129.0, 135.5, 136.6, 136.9, 142.3, 148.5, 149.4. IR v (neat, cm”1): 3283, 3053, 2966, 2870, 1493, 1465, 1430, 1313. MS (ESI) m/z: 460 (M+H)+.Anal. Calcd. for C24H33N3O2S2- 1/2H2O: C, 61.50; H, 7.31; N, 8.97. Found: C, 61.53; H, 7.36; N5 8.99.

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; VICORE PHARMA AB; WO2006/109048; (2006); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem