Category: imidazoles-derivatives

Reference of 17325-26-7,Some common heterocyclic compound, 17325-26-7, name is Methyl 1H-imidazole-5-carboxylate, 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.

To a solution of methyl lH-imidazole-4-carboxylate (1.26 g, 10.0 mmol, 1.0 eq) in DMF (18.0 mL) was added K2C03 (3.5 g, 25.0 mmol, 2.5 eq), followed by 2- (trimethylsilyl)ethoxym ethyl chloride (2.3 mL, 13.0 mmol, 1.3 eq). The reaction mixture was stirred at 80 C for 12.0 h, then cooled and quenched by water (100.0 mL) and extracted with EA (50.0 mL X 2). The combined organic layers were dried over Na2S04, filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (EA/PE=l/30, v/v) to provide methyl l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole-4- carboxylate (1.08 g, 42.5%).

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

Reference:
Patent; LIFESCI PHARMACEUTICALS, INC.; MCDONALD, Andrew; QIAN, Shawn; (346 pag.)WO2018/11628; (2018); 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. 36947-68-9, name is 2-Isopropyl-1H-imidazole, A new synthetic method of this compound is introduced below., Safety of 2-Isopropyl-1H-imidazole

To a stirred solution of 157 2-isopropyl-1H-imidazole (80.0 g, 0.73 mol) in 12 DMF (800 mL) at 0 C. was added 105 K2CO3(301 g, 2.2 mol) followed by 51 bromoacetonitrile (77 mL, 1.1 mol). Then the reaction mixture was allowed to stir at rt for 16 h. The mixture was diluted with EtOAc (800 mL) and water (1 L), the organic layer was separated and the aqueous layer was extracted with EtOAc (2×1 L). The combined organic extracts were dried over Na2SO4 and the solvent was removed by evaporation. Purification (FCC, SiO2, 30-40% EtOAc/hexanes) afforded the title compound (58.3 g, 54%) as a dark brown oil. 1H NMR (400 MHz, CDCl3) delta 7.00 (d, 1H, J=1.6 Hz), 6.94 (d, 1H, J=1.6 Hz), 4.89 (s, 2H), 3.05-3.01 (m, 1H), 1.37-1.35 (d, 6H, J=6.8 Hz).

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; Dart NeuroScience, LLC; Bookser, Brett; Botrous, Iriny; Branstetter, Bryan; Dyck, Brian; Weinhouse, Michael; US2019/177327; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 10040-98-9, A common heterocyclic compound, 10040-98-9, name is 4-Imidazol-1-yl-benzaldehyde, molecular formula is C10H8N2O, 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 mixture of malonitrile (60.0 mg, 0.9 mmol) and 4-(1H-imidazol-1-yl)benzaldehyde (155.0 mg, 0.9 mmol) in anhydrous ethanol ( 4.0 mL) was charged with N-methylmorpholine (0.1 mL, 0.9 mmol) for 2 minutes. To the mixture was added 3-benzyl-1-methyl-1H-pyrazol- 5(4H)-one (170.0 mg, 0.9 mmol) in one portion at room temperature. The reaction mixture was stirred at room temperature for 48 hrs. The suspension was filtered under vacuum and off white solid was obtained. The solid was gently washed with hexanes (20 mL) and chilled ethanol (10 mL) and further dried under high vacuum to provide compound 21 as an off white solid (330 mg, 89%).1H NMR (400 MHz, DMSO-d6) delta (ppm): 8.20 (s, 1H), 7.69 (s, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 7.15-7.08 (m, 6H), 6.86 (d, J = 7.2 Hz, 2H), 4.46 (s, 1H), 3.66 (s, 3H), 3.53 (d, J = 15.2 Hz, 1H), 3.28 (s, 1H). MS (ESI): Calcd for C24H20N6O: 408, found: 409 (M+H)+.

The synthetic route of 10040-98-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NANTBIOSCIENCE, INC.; TAO, Chunlin; YU, Chengzhi; POLAT, Tulay; YAN, Chao; RABIZADEH, Shahrooz; THEODORESCU, Daniel; (108 pag.)WO2016/205460; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 496-46-8, 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.

3a-isopropylglycoluril dimer diether (compound 2.3) (1 g, 2.5 mmol) and unsubstituted glycoluril (720 mg, 5.0 mmol) were mixed in 7M hydrochloric acid (12 mL). The mixture was stirred at room temperature for 1 hr. The mixture was heated to 100C for 2-3 hr. Evaporation of the acid in vacuo gave the a, P, 5, G-TETRAISOPROPYLCUCURBIT [4,2] uril as the major product.

The synthetic route of 496-46-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UNISEARCH LIMITED; WO2005/26168; (2005); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 760212-58-6, 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. 760212-58-6, name is 1-(4-Bromophenyl)-2-phenyl-1H-benzo[d]imidazole belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

1.0 g (2.9 mmol) of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole, 1.5 g (3.2 mmol) of 9,10-di(2-naphtyl)anthracene-2-boronic acid, and 0.067 g (0.058 mmol) of tetrakis(triphenylphosphine)palladium were dissolved into 20 mL of 1,2-dimethoxyethane. Then, 10 mL of a 2 M aqueous solution of sodium carbonate were added, and the whole was refluxed under heating for 8 hours in an argon atmosphere. After the completion of the reaction, the resultant was filtered, and the resultant solid was washed with water, methanol, and toluene to obtain 1.7g of a greenish white solid (84% yield) . Mass spectral analysis confirmed that the solid was a target product. The solid had an m/e of 698 with respect to a molecular weight of 698.27.

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

Reference:
Patent; IDEMITSU KOSAN CO., LTD.; EP1734038; (2006); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 33468-69-8,Some common heterocyclic compound, 33468-69-8, name is 4-(Trifluoromethyl)-1H-imidazole, molecular formula is C4H3F3N2, 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.

Sodium hydride (60% in mineral oil; 0.4 g, 10 mmol) was added portionwise to a stirred solution of 4-(trifluoromethyl)-lH-imidazole (1.15 g, 8.45 mmol) in THF (19 mL) at 0 C. After stirring at 0 C for 30 minutes 2-(trimethylsilyl)ethoxymethyl chloride (1.69 g, 10 mmol) was added and the reaction mixture was stirred at room temperature for 30 minutes. Water was added and the product extracted with EtOAc. The organic layer was separated, dried (MgS04), filtered and the solvent was evaporated in vacuo to yield 4-(trifluoromethyl)-l-{[2-(trimethylsilyl)ethoxy]methyl}- lH-imidazole (2.2 g, 98 % yield) that was used in the next step without further purification.

The synthetic route of 33468-69-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; TRABANCO-SUAREZ, Andres, Avelino; DELGADO-JIMENEZ, Francisca; VEGA RAMIRO, Juan, Antonio; TRESADERN, Gary, John; GIJSEN, Henricus, Jacobus, Maria; OEHLRICH, Daniel; WO2012/85038; (2012); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 17325-26-7, 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. 17325-26-7, name is Methyl 1H-imidazole-5-carboxylate belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 25-1 (0.5g, 4.0mmol) in anhydrous THF (15ml) in a dried flask was added NaH (O.lg, 4.8mmol) in portions. Once bubbling had subsided iodopropane (0.8ml, 8.0mmol) was added and stirred at room temperature overnight. To the reaction mixture was added another 0.5eq of NaH was added along with 3eq of iodopropane. After stirring for 5Oh another 0.5eq of NaH was added along with 2eq of iodopropane. The reaction mixture stirred for another 2Oh before being quenched with ethanol (5ml). Solvent removal afforded the desired product 25-2 as a solid. MS calculated M+H: 169.2, found 155.1 (M-CH2).

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, Methyl 1H-imidazole-5-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK & CO., INC.; WO2006/135627; (2006); A2;,
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

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

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