Month: December 2020

A common heterocyclic compound, 496-46-8, name is Tetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-dione, molecular formula is C4H6N4O2, 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. 496-46-8.

3a-Methylglycoluril 1 (0.26 g, 1.67 mmol), glycoluril 2 (1.42 g, 10 mmol) and paraformaldehyde (0.9 g, 30 mmol) were added to concentrated hydrochloric acid (5 ml), and the resultant mixture was heated at 95 C for 24 h. After evaporation of the solvent, the residue was added to water (300 ml) and heated under stirring. The white solid was filtered, and then added to a mixed solvent (30 ml) consisting of formic acid and acetic acid in a ratio of 2:1 (v/v). After thorough stirring, the insoluble material (CB[6]) was removed by filtration, and acetone was added to the acidic filtrate. The precipitates generated therein were collected to afford the desired product 4 in a yield of 14%. TOF mass: m/z 1033 (M+Na+). 1H NMR (500 MHz, in D2O with Na2SO4): delta 5.66 (d, Jin,out = 15.8 Hz, 11H, methylene Hout), 5.59 (d, Jin,out = 16 Hz, 1H, methylene Hout), 5.55 (s, 10H, methine H), 5.29 (s, 1H, methine H), 4.35 (d, Jin,out = 16 Hz, 1H, methylene Hin), 4.28 (d, Jin,out = 15.8 Hz, 11H, methylene Hin) and 1.75 ppm (s, 3H, methyl H). 13C NMR (125 MHz, in D2O with Na2SO4): delta 157.7 (C’O), 157.2 (CO), 77.1 (CH), 74.8 (C-CH3), 71.0 (CH), 52.1 (CH2), 48.1 (CH2) and 20.2 ppm (CH3).

The synthetic route of Tetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-dione has been constantly updated, and we look forward to future research findings.

Reference:
Article; Ahmed, Mostafa M.; Koga, Kazutaka; Fukudome, Makoto; Sasaki, Hideaki; Yuan, De-Qi; Tetrahedron Letters; vol. 52; 36; (2011); p. 4646 – 4649;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

A common heterocyclic compound, 583-39-1, name is 2-Mercaptobenzimidazole, molecular formula is C7H6N2S, 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. 583-39-1.

Acetic anhydride (30 mL, 0.033 mol) was added to 1H-benzo[d]imidazole-2(3H)-thione 1 (5 g,0.033 mol) and the stirred mixture was heated to 110-115 C for 30 min. The solution was cooledthen water (150 mL) was added, and finally kept for 30 min at room temperature. Colorless crystalswere filtered off (6.21 g, 97% Yield); TLC, Rf = 0.773 (1:1, n-hexane:ethyl acetate). The product wasrecrystallized from benzene to give white crystals. m.p. 201-202 C, (lit. [21] m.p., 195 C); IR (KBr) nu 1716 (C=O), 1368 (CH3), 2996 (CH aliphatic), and 3146 (CH aromatic), 1591 cm-1 (C=C). 1H-NMR(CDCl3/D2O) delta: 1.92 (s, 3H, CH3), 7.19 (m, 2H, Ar-H), and 7.26 ppm (m, 2H, Ar-H). 13C-NMR(DMSO-d6) delta: 27.1 (CH3), 108.5 (CH), 114.3 (CH), 122.3 (CH), 124.3 (CH), 129.8 (C), 130.1 (C), 168.9(C=S), and 171.1 ppm (C=O).

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

Reference:
Article; El Ashry, El Sayed H.; Kilany, Yeldez El; Nahas, Nariman M.; Barakat, Assem; Al-Qurashi, Nadia; Ghabbour, Hazem A.; Fun, Hoong-Kun; Molecules; vol. 21; 1; (2016);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

4887-80-3, 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. 4887-80-3, name is 5-Methoxy-1H-benzo[d]imidazole, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of NaH (972 mg, 40.5 mmol) in DMF (20 mL) was added 5- methoxy-lH-benzo[d] imidazole (2.0 g, 13.5 mmol) at 27C. After stirring for 5 minutes, Mel (2.3 g, 16.2 mmol) was added and the resulting mixture was stirred for 16 h. The mixture was then diluted with water (100 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine (30 mL), dried over Na2S04 and concentrated to give the crude product (1.2 g, 54.5%) as a grown solid. This crude was used in next step without further purification. LCMS (m/z): 163.1 (M+l).

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; EPIZYME, INC.; DUNCAN, Kenneth, W.; CHESWORTH, Richard; BORIACK-SJODIN, Paula, Ann; MUNCHHOF, Michael, John; JIN, Lei; WO2014/100730; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 10111-08-7, name is Imidazole-2-carboxaldehyde, molecular formula is C4H4N2O, 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. 10111-08-7

(Reference Example 21) Synthesis of 1-isopropyl-1H-imidazole-2-carbaldehyde: Potassium carbonate (0.863 g, 6.24 mmol) and 2-iodopropane (0.614 mL, 6.24 mmol) were added to a solution of 1H-imidazole-2-carbaldehyde (0.500 g, 5.20 mmol) in N,N-dimethylformamide (5.2 mL) at room temperature and the reaction liquid was stirred at 60C for 4 hours. The reaction liquid was cooled to room temperature and ethyl acetate and distilled water were added to the reaction liquid. The organic layer was washed with a 10% aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate) to obtain 1-isopropyl-1H-imidazole-2-carbaldehyde (0.355 g, 2.57 mmol, 49%) as a colorless oil. 1H-NMR (400 MHz, CDCl3) delta: 1.48 (3H, d, J=6.4 Hz), 1.48 (3H, d, J=6.4 Hz), 5.48 (1H, quint, J=6.4 Hz), 7.30 (1H, s), 7.33 (1H, s), 9.83 (1H, s). ESI-MS: m/z= 139 (M+H)+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 10111-08-7, its application will become more common.

Reference:
Patent; Toray Industries, Inc.; ARAI Tadamasa; MORITA Yasuhiro; UDAGAWA Shuji; ISEKI Katsuhiko; IZUMIMOTO Naoki; (95 pag.)EP3263565; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

4597-21-1, These common heterocyclic compound, 4597-21-1, name is 1,2-Dimethyl-1H-benzo[d]imidazole-5-carbaldehyde, 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.

Grignard reagent was prepared in an oven-dried three necked flask outfitted with a reflux condenser, dropping funnel, and magnetic stirrer. 3,5-dimethoxy-bromobenzene (2.0 g, 9.0 mmol) in THF (10 mL) was added to a mixture of magnesium turning (0.2 g, 9.0 mmol) in THF (5 mL) with a small piece of iodine. The resulting mixture was refluxed for about 3 h then cooled to room temperature for about 30 min. The (3,5-dimethoxyphenyl)magnesium bromide was then added slowly to a stirred solution of 1,2-dimethoxy-1H-benzoimidazole-5-carbaldehyde (1.3 g, 7.5 mmol) in THF (10 mL) at 0 C. After complete addition, the solution was allowed to stir at room temperature for about 1 h. The mixture was cooled to 0 C. and quenched with saturated NH4Cl solution (40 mL). The aqueous layer was extracted with EtOAc (3¡Á20 mL). The combined organic layers were washed with water (2¡Á30 mL), brine (30 mL) and dried (MgSO4). Solvent was removed and the crude product was slurried in hexane to afford (3,5-dimethoxy-phenyl)-(1,2-dimethyl-1H-benzoimidazlo-5-yl)-methanol (2.1 g, 91%) as a off white solid: 1H NMR (CDCl3) delta 7.66 (s, 1H), 7.24-7.20 (dd, J=1, 8 Hz, 1H), 7.17 (d, J=8 Hz, 1H), 6.56 (d, J=2 Hz, 2H), 6.31 (t, J=2 Hz, 1H), 5.84 (s, 1H), 3.72 (s, 6H), 3.63 (s, 3H), 3.55 (b, 1H), 2.52 (s, 3H). A suspension of (3,5-dimethoxy-phenyl)-(1,2-dimethyl-1H-benzoimidazol-5-yl)-methanol (2.1 g, 6.7 mmol) and MnO2 (2.9 g, 33.6 mmol) in CH2Cl2 (300 mL) was stirred at room temperature for 17 h. The mixture was filtered through celite and solvent was removed. The crude product was slurried with ether to afford (3,5-dimethoxy-phenyl)-(1,2-dimethyl-1H-benzoimidazol-5-yl)-methanone (2.0 g, 99%) as an off white solid: 1H NMR (DMSO-d6) delta 7.90 (s, 1H), 7.71-7.62 (m, 2H), 6.80 (s, 3H), 3.80 (s, 3H), 3.35 (s, 3H), 2.58 (s, 3H); 13C NMR (DMSO-d6) delta 195.28, 160.17, 154.83, 141.54, 140.27, 139.15, 130.15, 123.50, 120.73, 109.70, 107.19, 103.62, 55.47, 29.96, 13.52. 3-(3,5-Dimethoxy-phenyl)-3-(1,2-dimethyl-1H-benzoimidazol-5-yl)-acrylonitrile (E and Z isomers) were prepared analogously to 3-(3-amino-4-methoxy-phenyl)-3-(3,4-dimethoxy-phenyl)-acrylonitrile (E and Z isomers) using (3,5-dimethoxy-phenyl)-(1,2-dimethyl-1H-benzoimidazol-5-yl)-methanone (2.0 g, 6.4 mmol), lithium bis (trimethylsilyl)amide (7.7 mL, 7.7 mmol) and diethyl cyanomethylphosphate (1.4 g, 7.7 mmol). The crude product was purified by flash chromatography (silica gel, CH2Cl2:CH3OH 95:5) to afford mixture of isomers of 3-(3,5-dimethoxy-phenyl)-3-(1,2-dimethyl-1H-benzoimidazol-5-yl)-acrylonitrile (1.1 g, 50%) as a white solid: mp 199-201 C.; 1H NMR (CDCl3) delta 7.69 (m, 3H), 6.56-6.42 (m, 3H), 5.70 (5.74) (s, 1H), 3.77 (s, 3H), 3.73 (3.74) (s, 6H), 2.61 (s, 3H); 13C NMR (CDCl3) delta 163.76 160.63 (160.60), 153.22 (153.54), 142.35 (142.57), 141.69 (139.43), 137.04 (137.38), 130.69 (132.54), 123.74 (122.64), 120.81 (119.54), 118.23 (118.09), 108.84 (108.80), 107.02 (107.72), 102.08 (102.02), 94.32 (93.47), 55.42 (55.41), 30.05 (30.00), 13.88; Anal Calcd for C20H19N3O2+0.2H2O: C, 71.28; H, 5.80; N, 12.47. Found: C, 71.18; H, 5.86; N, 12.42.

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 4597-21-1.

Reference:
Patent; Muller, George W.; Man, Hon-Wah; US2006/52596; (2006); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

These common heterocyclic compound, 1964-77-8, name is 5-Bromo-2-methyl-1H-benzo[d]imidazole, 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. 1964-77-8

To 5-bromo-2-methylbenzimidazole (38 g, 180 mmol) in TEtaF (400 mL) was added di-tert-buty dicarbonate (39 g, 189 mmol). The reaction mixture was stirred at room temperature for 24 h and then concentrated. Ethyl acetate (400 mL) was added to the residue, and the solution was washed with 10% aqueous citric acid (2 x 100 mL), water (100 mL), and brine (100 mL), dried over sodium sulfate, and concentrated. Column chromatography on silica (gradient 20-30% ethyl acetate in hexane) provided 1,1 -dimethyl 6-bromo-2-methyl-lH-benzimidazole-l-carboxylate (27 g, 48% yield) as a beige solid. MS (EI) for Ci3Hi5BrN2O2: 312 (MH+).

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 1964-77-8.

Reference:
Patent; EXELIXIS, INC.; AAY, Naing; ARCALAS, Arlyn; BOWLES, Owen, Joseph; BUSSENIUS, Joerg; CURTIS, Jeffry, Kimo; DEFINA, Steven, Charles; DUBENKO, Larisa; HARRIS, Jason, R.; JACKSON-UGUETO, Eileen, E.; MANALO, Jean-Claire, Limun; KIM, Angie, Inyoung; PACK, Michael; PETO, Csaba, J.; RICE, Kenneth, D.; TSANG, Tsze, H.; WO2010/138487; (2010); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

68282-53-1, Adding some certain compound to certain chemical reactions, such as: 68282-53-1, name is 5-Methyl-1H-imidazole-4-carbaldehyde, 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 68282-53-1.

COMPOUND 12.1. 20: 4- {5. 8-DIMETHOXY-2-rf4-METHYL-l-IMIDAZOL-5- YL)METHYL]-1,2,3,4-TETRAHYDROISOQUINOLIN-1-YL}-N,N- DIETHYLBENZAMIDE; INTERMEDIATE 5.1. 10 (115 mg, 0.31 mmol) and 4-methyl-5- imidazolecarbaldehyde (108 mg, 0.62 mmol) were dissolved in DCE (5.0 mL). After stirring for 10 min at room temperature, sodium triacetoxyborohydride (197 mg, 0.93 mmol) was added and the mixture was stirred for 18 h at room temperature. DCM and 1 M sodium hydroxide solution were added and the mixture was passed through a Whatman 1PS silicon-treated filter paper. The organic phase was evaporated and the crude product was purified by flash chromatography to yield the product (103 mg, 0. 20 mmol, 65%).’H NMR (500 MHz, CDC13) : 8 0. 99, 1.18 (2 brs, 6H), 2.58-2. 74, 3.17-3. 50 (2 m, 8H), 3.32, 3.35 (2 s, 6H), 3.44, 3.65 (2 d, J 12.0 Hz, 2H), 5.05 (s, 1H), 6.51, 6.63 (2 d, J 9. 0 Hz, 2H), 6.87 (s, 1H), 7.00, 7.14 (m, 4H), 7. 21 (m, 5H), 7.80 (d, J 3. 5 Hz, 2H).

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 68282-53-1.

Reference:
Patent; ASTRAZENECA AB; WO2005/61484; (2005); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

139481-44-0, name is Methyl 1-((2′-cyano-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate, 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. 139481-44-0

Raw material (compound 2A) 20 g, in the reaction bottle, adding ethanol to 200 ml, triethylamine 5 g, 50% aqueous hydroxylamine solution 37 g, reaction 24h, the cooling crystallization, the white solid obtained 13.6 g (63.0%). HPLC detection reaction in the reaction solution at the end of the major amide impurity (compound 6A): product is 7.15% : 92.84% (that is, the impurity and the product of the ratio of 1 : 12.9), see Figure 2.

Statistics shows that 139481-44-0 is playing an increasingly important role. we look forward to future research findings about Methyl 1-((2′-cyano-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate.

Reference:
Patent; Shanghai Institute of Pharmaceutical Industry; China State Institute of Pharmaceutical Industry; Wang, Xiaomei; Sui, Qiang; Tang, Chao; Liu, Shuai; Ouyang, Qunxiang; Shi, Huilin; (17 pag.)CN103664792; (2016); B;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1792-40-1, A common compound: 1792-40-1, name is 2-Methyl-5-nitro-1H-benzo[d]imidazole, 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.

General procedure: 1/3-Butyl-2-methyl-5-nitro-1H/3H-benzimidazole was synthesized by previous reported method by the alkylation of 2-methyl-5-nitro-benzimidazole (0.05 mol) with butyl bromide (0.075 mol) in the presence of NaH (0.126 mol) in THF at room temperature for 8h. To a suspension of SnCl2.2H2O (135 mmol) in 2 N HCl (95.2 ml), 1/3-butyl-2-methyl-5-nitro-1H/3H-benzimidazole (36.4 mmol) was heated at 110 C for 7 h. After the completion of the reaction (monitored by TLC), the suspension was neutralized with 2 N NaOH and diluted with ethanol. Filtered the solid product and extracted the filtrate with chloroform, dried over Na2SO4, filtered and concentrated to get mixture of products which were separated through column chromatography using ethylacetate:methanol (9.5:0.5) to get pure solid compounds 2b and 2d.

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, 2-Methyl-5-nitro-1H-benzo[d]imidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Sharma, Alka; Luxami, Vijay; Paul, Kamaldeep; European Journal of Medicinal Chemistry; vol. 93; (2015); p. 414 – 422;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

3034-50-2, Adding a certain compound to certain chemical reactions, such as: 3034-50-2, name is Imidazole-4-carbaldehyde, 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 3034-50-2.

12.0 g (124 mmol) 4-formyl-imidazole are placed together with 750 mg Raney nickel in 1000 ml of methanolic ammonia solution and shaken at 40¡ã C. for 30 min. Then the mixture is hydrogenated in a Parr apparatus under a hydrogen atmosphere at 5 bars pressure at 40¡ã C. for 14 h. Another 750 mg Raney nickel are then added and the mixture is again hydrogenated at 50¡ã C. under a hydrogen atmosphere at 5 bars pressure for 14 h. The mixture is filtered, evaporated down i. vac., and in each case methanol, toluene and ethanol are added to the residue and it is again evaporated down completely i. vac. The residue is combined with ethereal hydrochloric acid in methanol and evaporated down completely i. vac. The residue is in each case combined with methanol and dichloromethane and evaporated down completely i. vac.Yield: 21.2 g (quant.)Rt value: 0.49 min (D)C4H7N3*2 HCl (170.04/97.12)Mass spectrum: (M+H)+=98

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, Imidazole-4-carbaldehyde, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Dahmann, Georg; Gerlach, Kai; Pfau, Roland; Priepke, Henning; Wienen, Wolfgang; Schuler-Metz, Annette; Nar, Herbert; US2008/51578; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem