Category: imidazoles-derivatives

Application of 20485-43-2, 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. 20485-43-2, name is 1-Methyl-1H-imidazole-2-carboxylic acid belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Example 101-4; N- [3- ( {2- [ (cyclopropylcarbonyl) amino] [1,3] thiazolo [5, 4-b] pyridin- 5-yl } oxy) phenyl] -l-methyl-lH-imidazole-2-carboxamide; A mixture of N- [5- (3-aminophenoxy) [1, 3] thiazolo [5, 4- b]pyridin-2-yl] cyclopropanecarboxamide (175 mg, 0.536 mmol) , 1- methyl-lH-imidazole-2-carboxylic acid (101 mg, 0.804 mmol), HATU (367 mg, 0.965 mmol), N,N-diisopropylethylamine (420 muL, 2.41 mmol) and N,N-dimethylformamide (5 mL) was stirred at room temperature for 15 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, hexane/ethyl acetate=50/50->0/100) and recrystallized from ethyl acetate-tetrahydrofuran to give the title compound (152 mg, 65%) as a white solid. 1H-NMR (DMSO-d6, 300 MHz) delta 0.94 – 1.01 (4H, m) , 1.95 – 2.04 (IH, m) , 3.97 (3H, s) , 6.86 – 6.91 (IH, m) , 7.07 – 7.15 (2H, m) , 7.38 (IH, t, J = 8.1 Hz), 7.44 (IH, d, J = 0.3 Hz), 7.67 – 7.74 (2H, m), 8.18 (IH, d, J = 9.0 Hz), 10.47 (IH, s) , 12.70 (IH, 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, 1-Methyl-1H-imidazole-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; WO2008/150015; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 33543-78-1, name is Ethyl 1H-imidazole-2-carboxylate, 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 33543-78-1, category: imidazoles-derivatives

SEMCI (1.519 ml_, 8.56 mmol) was added to a DMF (10 mL) suspension of K2C03 (1.972 g, 14.27 mmol) and ethyl imidazole-2-carboxylate (CAS 33543-78-1 ) (1 g, 7.14 mmol). After the mildly exothermic reaction subsided, the mixture was allowed to stir one hour at room temperature and was quenched with the addition of water and ethyl acetate. The organic phase was washed with water, brine, dried (sodium sulfate), filtered and concentrated. Purification of the residue by FCC (100percent Heptane to 50percent ethyl acetate/Heptane) afforded the title compound. MS (ESI+) m/z 271.4 (M+H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 1H-imidazole-2-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; NOVARTIS AG; BELANGER, David B.; FLOHR, Stefanie; GELIN, Christine Fang; JENDZA, Keith; JI, Nan; LIU, Donglei; LORTHIOIS, Edwige Liliane Jeanne; KARKI, Rajeshri Ganesh; MAINOLFI, Nello; POWERS, James J.; RANDL, Stefan Andreas; ROGEL, Olivier; VULPETTI, Anna; YOON, Taeyoung; WO2015/9977; (2015); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 124312-73-8,Some common heterocyclic compound, 124312-73-8, name is (1-Methyl-1H-imidazol-2-yl)methanamine, molecular formula is C5H9N3, 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.

The compound (225 mg) obtained in Example 55-3 was dissolved in methanol (4.0 ml). The solution was added with the compound (64.5 mg) obtained in Example 14-7 and trimethyl orthoformate (0.13 ml) and the whole was stirred at room temperature for 1.5 hours. After having been cooled to 0C, the reaction solution was added with sodium borohydride (20.8 mg) and the whole was stirred at room temperature for 20 minutes. After the reaction solution was concentrated under reduced pressure, the resultant residue was added with distilled water and the whole was subjected to extraction with chloroform. The organic layer was washed with a saturated saline solution and dried with an anhydrous sodium sulfate. The drying agent was filtrated out and then the organic layer was concentrated under reduced pressure. The resultant was dissolved in methanol (6.0 ml). The reaction solution was added with 2-imidazole carboxaldehyde (83.3 mg) and sodium cyanoborohydride (77.3 mg). The whole was added with acetic acid to adjust the pH to 5 and stirred at room temperature for 18 hours. The reaction solution was concentrated under reduced pressure. The resultant residue was added with a 1 mol/l sodium hydroxide aqueous solution and the whole was subjected to extraction with chloroform. The organic layer was washed with a saturated saline solution and dried with anhydrous sodium sulfate. The drying agent was filtrated out and then the organic layer was concentrated under reduced pressure. The resultant residue was purified through silica gel column chromatography (hexane/ethyl acetate) and treated with hydrochloric acid, thereby obtaining a hydrochloride (174.3 mg) of the subject compound as a white solid. MS(FAB,Pos.):m/z=567[M+H]+ 1H-NMR(500MHz,DMSO-d6):delta=0.90(6H,t,J=7.3Hz),1.64-1.86(8H,m),2.95(4H,br),3.05(2H,br),3.28(2H,br),3.67(3H,s),3.83(2H,s),4.10(2H,s),4.17(2H,s),5.94(2H,s),7.31-7.39(5H,m),7.49-7.54(3H,m),7.60(2H,s),7.72(1H,d,J=8.4Hz),8.17(1H,s),10.43(1H,br),14.94(2H,br).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (1-Methyl-1H-imidazol-2-yl)methanamine, its application will become more common.

Reference:
Patent; Kureha Corporation; EP1724263; (2006); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 137049-00-4, name is 1-Methyl-1H-imidazole-4-sulfonyl chloride, 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 137049-00-4, category: imidazoles-derivatives

3-Isopropyl-2-oxo-2,3-dihydrobenzoimidazole-1-carboxylic acid [(1S,3R,5R)-8-((S)-2-hydroxy-3-methylaminopropyl)-8-azabicyclo[3.2.1]oct-3-yl]amide TFA salt, (prepared as described in Example 12, step (f)), (0.050 g, 0.078 mmol) was suspended in dimethylformamide (5 mL) and cooled to 0 C. N,N-diisopropylethylamine (0.43 mL, 24.6 mmol) was added, followed by 1-methyl-1-H-imidazole sulfonyl chloride (0.017 g, 0.094 mmol). The reaction was allowed to reach room temperature and was judged to be complete after about 1 hr. The reaction was quenched with acetic acid and water (1:1). Volatiles were removed and purification via prep HPLC (reverse phase) was accomplished on a gradient of 15-45% over 50 min; flow rate 20 mL/min, to provide the title compound (0.030 g, 56%) as a TFA salt. (m/z): [M+H]+ calcd for C26H37N7O5S 560.27; found 560.5. Retention time (anal. HPLC: 2-50% MeCN/H2O over 4 min)=4.05 min. 1H NMR (d6-DMSO): 9.28 (d, 1H), 8.08 (d, 1H), 7.79 (d, 2H), 7.45 (d, 1H), 7.21 (m, 2H), 4.75 (br m, 2H), 4.01 (m, 1H), 3.71 (br s, 4H), 3.23 (m, 3H), 2.88 (m, 1H), 2.77 (s, 2H), 2.29 (m, 2H), 2.08 (m, 2H), 1.93 (m, 4H), 1.59 (m, 2H), 1.48 (d, 6H).

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-Methyl-1H-imidazole-4-sulfonyl chloride, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Theravance, Inc.; US2006/276482; (2006); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 20485-43-2,Some common heterocyclic compound, 20485-43-2, name is 1-Methyl-1H-imidazole-2-carboxylic acid, 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.

General procedure: A mixture of 1-methyl-1H-imidazole-2-carboxylic acid (0.130 g,1mmol), EDC.HCl (0.29 g, 1.5mM), HOBt (0.20 g, 1.5mmol) and Et3N(0.15 g, 1.5 mM) in dichloromethane (10 mL) was stirred for 1 h at 0 C. Then, L-phenylalanine methyl ester.HCl (1.05 mM) was added into the solution. The reaction mixture was stirred for 12 h at 25 Cand then evaporated to dryness. The ester obtained was washed with water and extracted with dichloromethane (Scheme 1). To a solutionof the ester (1 equiv) in a dichloromethane/methanol (9:1 v/v)mixture, was added a methanolic solution of NaOH (3 equiv) withfinal concentration of the alkali being about 0.1-0.2 N. The reaction was monitored by TLC for the disappearance of starting ester. After the completion of the reaction, the solvents were removed under vacuum and the residue was diluted with water. Then, the aqueous phase was acidified to pH 2-3 with dilute HCl and extracted with ethyl acetate. The combined organic layers were dried with anhydrous sodium sulfate (Na2SO4) and the solvent was removed to afford the acid (PAIC). Single crystal of PAIC was isolated by slow evaporation of the solvent. Yield: 143 mg (74%), M.P- 129 C; Anal.Calc. for C14H15N3O3: C, 61.53; H, 5.53; N, 15.38. Found C, 61.13; H,5.45; N,15.18; 1H NMR (DMSO-d6, 400MHz): delta/ppm3.16 (d, J 4Hz,2H, CH2), 3.8 (s, 3H, NeCH3), 4.6 (m, H, chiral H), 6.9e7.2 (m, 7H,Aromatic H), 8.2 (d, J 8.4 Hz, 1H, amide-NH); 13C NMR: 34.9 (CH3),36.2 (eCH2), 52.9 (CeNH), 158.5 (COeN), 172(eCOO); FT-IR (KBr, cm-1)1555 (NeH), 1602 (eC]N), 3292 (HOeCO), 1673 (C]Oamide), 2931 (CeH); ESI mass: m/z 272.9.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Methyl-1H-imidazole-2-carboxylic acid, its application will become more common.

Reference:
Article; Annaraj; Mitu; Neelakantan; Journal of Molecular Structure; vol. 1104; (2016); p. 1 – 6;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 1072-62-4, name is 2-Ethyl-1H-imidazole, molecular formula is C5H8N2, 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. Recommanded Product: 1072-62-4

2-Ethylimidazole (0.756 g, 7.9 mmol) dissolvedin acetonitrile (15 mL) was combined with potassium hydroxide (0.550 g, 9.8mmol) and stirred at 80C for 30 minutes. 2-(Chloromethyl)quinolinehydrochloride (1.45 g, 6.8 mmol) and potassium hydroxide (0.440 g, 7.8 mmol)were added and the mixture was stirred and heated at 80C overnight. Thereaction mixture was filtered to remove a white solid (presumed be potassiumchloride) and the volatiles were removed from the filtrate to yield a yellowoil. The oil was suspended with dichloromethane (25 mL) and washed with a basicaqueous solution (4 x 25 mL) and water (2 x 25 mL). The organic layers weredried with magnesium sulfate and concentrated to a yellow oil. The oil wasresuspended in acetonitrile and 2-(bromomethyl)naphthalene (1.50 g, 6.8 mmol)was added to the solution. The mixture was stirred and heated at 80Covernight. A solid precipitated from the hot acetonitrile. The white solid wasfiltered, washed with acetonitrile, and dried in air to yield 4-Br (.715 g, 23% yield). MP =215-216C. HRMS (ESI+) calcdfor C26H24N3+ [M-Br] of m/z =378.1965, found m/z = 378.1942. 1H NMR (500 MHz, DMSO- d6) delta = 8.48 (1H, d, Ar, J =8.3 Hz), 8.03 (2H, t, Ar, J = 8.8 Hz), 7.98 (1H, m, Ar), 7.93 (1H, m, Ar), 7.90(3H, m, Ar), 7.76 (2H, m, Ar), 7.61 (4H, m, Ar), 7.50 (1H, m, Ar), 5.88 (2H, s,CH2), 5.74 (2H, s, CH2), 3.17 (2H, q, CH2, J= 7.6 Hz) 0.94 (3H, t, CH3, J = 7.6 Hz). 13C NMR (125MHz, DMSO- d6) delta = 154.2(Ar), 149.1 (Ar), 146.7 (Ar), 137.4 (Ar), 132.7 (Ar), 132.5 (Ar), 132.4 (Ar),130.1 (Ar), 128.7 (Ar), 128.3 (Ar), 128.0 (Ar), 127.7 (Ar), 127.7 (Ar), 127.1(Ar), 126.9 (Ar), 126.7 (Ar), 126.6 (Ar), 126.4 (Ar), 125.0 (Ar), 123.1 (Ar),122.1 (Ar), 119.8 (Ar), 52.3 (CH2), 50.8 (CH2), 16.6 (CH2),11.2 (CH3).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1072-62-4, its application will become more common.

Reference:
Article; DeBord, Michael A.; Wagers, Patrick O.; Crabtree, Steven R.; Tessier, Claire A.; Panzner, Matthew J.; Youngs, Wiley J.; Bioorganic and Medicinal Chemistry Letters; vol. 27; 2; (2017); p. 196 – 202;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference 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.

To a solution of 2-isopropyl-lH-imidazole (155 mg) in N,N-dimethylformamide (4 ml), was added NaH (56.4 mg) portionwise. After stirring for 15 min at room temperature, 5-fluoro- 2-nitroaniline61 (200 mg) was added and the reaction mixture was heated at 60 C for 16 hours. The reaction mixture was diluted with ethyl acetate and washed with aq. sodium bicarbonate. The organic layer was dried over MgS04, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, eluent: 0 to 5% of methanol in dichloromethane) to afford 5-(2-isopropyl-lH-imidazol-l-yl)-2-nitroaniline (85mg, 27%) as an orange solid. MS (ISP): 247.2 ([M+H]+).

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; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; GOERGLER, Annick; NORCROSS, Roger; DEY, Fabian; KUSZNIR, Eric Andre; (206 pag.)WO2019/43217; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 16042-25-4, These common heterocyclic compound, 16042-25-4, name is 2-Imidazolecarboxylic acid, 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.

lH-Imidazole-2-carboxylic acid (100 mg, 0.892 mmol), 1,4- dichloro-2-(chloromethyl)benzene (382 mg, 1.96 mmol), and K2C03 (370 mg, 2.68 mmol) were combined in DMF. The suspension was stirred at 100 C for 1 h, then added to 5% aqueous HC1 and extracted with EtOAc. The organic phase was washed with saturated aqueous NaHC03, H20, and brine, then dried over Na2S04 and the solvent removed under reduced pressure. The crude residue was purified by flash- column chromatography using a gradient of DCM : MeOH (100 : 0 to 98 : 2) to give 62a (290 mg, 76%) as a yellow oil.

Statistics shows that 2-Imidazolecarboxylic acid is playing an increasingly important role. we look forward to future research findings about 16042-25-4.

Reference:
Patent; ARDELYX, INC.; LEWIS, Jason, G.; REICH, Nicholas; CHEN, Tao; JACOBS, Jeffrey W.; CHARMOT, Dominique; NAVRE, Marc; FINN, Patricia; CARRERAS, Christopher; SPENCER, Andrew; WO2013/96771; (2013); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, 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 1003-21-0, name: 5-Bromo-1-methyl-1H-imidazole

[0206] A solution of isopropylmagnesium chloride/lithium chloride complex (1.3 M in THF, 19.5 mE, 25.35 mmol) was added dropwise by syringe to a solution of 5-bromo-1-me- thyl-1H-imidazole (4.12 g, 25.58 mmol) in dry THF (130 mE) at 0 C. After 15 minutes, the Grignard solution was added via cannulation to a solution of picolinaldehyde (2.0 ml, 20.93 mmol) in dry THF (55 mE) at 0 C. The reaction mixture was stirred for 5 minutes at 0 C., then warmed to room temperature for 1 hour. The reaction mixture was then cooled in an ice bath and quenched with saturated aqueous ammonium chloride. The mixture was partitioned between brine and ethyl acetate. The separated aqueous phase was further extracted with ethyl acetate. The organic phase was dried (Na2504), filtered, and concentrated. The crude product was purified by flash column chromatography (silica gel, 0-5% MeOH-DCM) to provide the title compound as a white solid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Bromo-1-methyl-1H-imidazole, and friends who are interested can also refer to it.

Reference:
Patent; Janssen Pharmaceutica NV; Leonard, Kristi A.; Barbay, Kent; Edwards, James P.; Kreutter, Kevin D.; Kummer, David A.; Maharoof, Umar; Nishimura, Rachel; Urbanski, Maud; Venkatesan, Hariharan; Wang, Aihua; Wolin, Ronald L.; Woods, Craig R.; Fourie, Anne; Xue, Xiaohua; Cummings, Maxwell D.; US2015/105365; (2015); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 131020-36-5, A common heterocyclic compound, 131020-36-5, name is Methyl 1-methyl-1H-benzo[d]imidazole-5-carboxylate, molecular formula is C10H10N2O2, 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.

Preparation of ( 1 -methyl- l H-benzimidazol- – l methanolThe title compound was synthesized by esterification of l//-benzimidazole-5-carboxylic acid using methanol in presence of cone, sulphuric acid followed by N-methylation using methyl iodide in presence of potassium carbonate and subsequent reduction of the ester group by lithium aluminium hydride; NMR (300 MHz, DMSO- 6) delta 3.84 (s, 3H), 4.59 (s, 2H), 5.23 (br s, l H), 7.26 (d, J = 8.4 Hz, 1H), 7.52-7.58 (m, 2H), 8.23-8.31 (m, 1 H).

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; GLENMARK PHARMACEUTICALS S.A.; LINGAM, Prasada, Rao, V., S.; THOMAS, Abraham; KHAIRATKAR-JOSHI, Neelima; BAJPAI, Malini; GULLAPALLI, Srinivas; DAHALE, Dnyaneshwar, Harishchandra; MINDHE, Ajit, Shankar; RATHI, Vijay, Eknath; WO2011/138657; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem