Author: Jessica.F

Some common heterocyclic compound, 41716-18-1, name is 1-Methyl-1H-imidazole-4-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. 41716-18-1

Preparation of Compound 69aAt 0¡ã C., a suspension of 1-methyl-1H-imidazole-4-carboxylic acid (100.9 mg, 0.8 mmol) in CH2Cl2 (8 mL) was added oxalylchloride (305 mg, 0.21 mL, 2.4 mmol) followed by addition of 1 drop of DMF. The mixture was stirred for 2 days at 25¡ã C. All solvent was removed in vacuo to give a crude 69a.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 41716-18-1, its application will become more common.

Reference:
Patent; Pfizer Inc.; US2009/318440; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

51605-32-4, A common heterocyclic compound, 51605-32-4, name is Ethyl 5-methyl-1H-imidazole-4-carboxylate, molecular formula is C7H10N2O2, 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.

Ethyl 2-bromo-4-methyl-1H-imidazole-5-carboxylate (EV-AT8648-001)? Step 1 To a stirred solution of ethyl 4-methyl-1H-imidazole-5-carboxylate (CAS 51605-32- 4, 500 mg, 3.24 mmol) in acetonitrile (10 ml) and chloroform (10 ml) was added N- bromosuccinimide (577 mg, 3.24 mmol) and the reaction stirred under a nitrogen atmosphere at room temperature for 18h. The reaction mixture was concentrated and the residue was purified by flash column chromatography (10-100percent ethyl acetate/heptane) to afford 560 mg (73percent) of ethyl 2-bromo-4-methyl-1H-imidazole-5-carboxylate (EV-AT8648-001) as an off-white solid. LCMS (method D): retention time 0.87 min, M/z = 233/235 (M + 1).

The synthetic route of 51605-32-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PADLOCK THERAPEUTICS, INC.; DEVRAJ, Rajesh; KUMARAVEL, Gnanasambandam; ATTON, Holly; BEAUMONT, Edward; GADOULEAU, Elise; GLEAVE, Laura; KERRY, Philip Stephen; LECCI, Cristina; MENICONI, Mirco; MONCK, Nat; PALFREY, Jordan; PAPADOPOULOS, Kostas; TYE, Heather; WOODS, Philip A.; (158 pag.)WO2017/147102; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding some certain compound to certain chemical reactions, such as: 312-73-2, name is 2-(Trifluoromethyl)-1H-benzo[d]imidazole, 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 312-73-2. 312-73-2

General procedure: A solution of this chloromethyl ester (1.8 mmol) in N,N-dimethylformamide (4 ml) was treated with the 2-substituted benzimidazoles (1.8 mmol) and cesium carbonate (2.8 mmol). The mixture was stirred for 3 h at r.t. and partitioned with water and ethyl acetate (20 ml). The aqueous layer was further extracted with ethyl acetate (20 ml) and the combined organic layers washed with brine (20 ml), dried (sodium sulfate), filtered and concentrated. Flash chromatography with ethyl acetate provided the desired product as colored oil.

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 2-(Trifluoromethyl)-1H-benzo[d]imidazole.

Reference:
Article; Sengupta, Prabal; Puri, Chetan S.; Chokshi, Hemant A.; Sheth, Chetana K.; Midha, Ajay S.; Chitturi, Trinadha Rao; Thennati, Rajamannar; Murumkar, Prashant R.; Yadav, Mange Ram; European Journal of Medicinal Chemistry; vol. 46; 11; (2011); p. 5549 – 5555;,
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 41716-18-1 as follows. 41716-18-1

A mixture of (+/-)-ferf-butyl ((c/s)-3-aminocyclohexyl)carbamate (5 g, 23.3 mmol) and DMAP (7.1 g, 58.3 mmol) in CH2CI2 (100 mL) was stirred at ambient temperature, then 1 -methyl-1 h-imidazole-4-carboxylic acid (2.9 g, 23.3 mmol) was added. After stirring for 10 minutes at room temperature, EDC (6.7 g, 35 mmol) was added. The mixture stirred for 18h at room temperature. The reaction mixture was washed with citric acid (5percent aq.), the organic layer was removed, dried (MgS04), the solids removed by filtration, and the solvent of the filtrate removed under reduced pressure to give (+/-)-f-butyl ((c/’s)-3-(1 -methyl-1 – -imidazole-4- carboxamido)cyclohexyl)carbamate. LC-MS ES+ m/z = 323.5; Rt: 0.75 min, method A.

According to the analysis of related databases, 41716-18-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JANSSEN SCIENCES IRELAND UC; JONCKERS, Tim, Hugo, Maria; RABOISSON, Pierre, Jean-Marie, Bernard; GUILLEMONT, Jerome, Emile, Georges; MC GOWAN, David, Craig; EMBRECHTS, Werner, Constant, Johan; COOYMANS, Ludwig, Paul; MICHAUT, Antoine, Benjamin; (162 pag.)WO2016/20526; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding some certain compound to certain chemical reactions, such as: 152628-03-0, name is 4-Methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylic acid, 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 152628-03-0. 152628-03-0

Example 1:Orthophosphoric acid (210 gms) was taken in round bottomed flask and Rho205 (210 gms) was added in portions with vigorous stirring. (Note: Sharp increase in temperature > 200 C). The above mass is allowed to cool to 70 C and 2-n-propyl- 4-methyl-benzimidazole-6-carboxylic acid (70 gms, 0.321 mol) was added slowly. Then N-methylbenzene-l,2-diamine hydrochloride (62.3 gms, 0.321 mol) was added in small portions at same temperature and then the temperature was raised to 125-130 C. After completion, reaction was quenched with ice cold water (1 Lt), adjusted pH of the reaction mixture to 9-10 by the addition of aqueous ammonia solution. Obtained solid was filtered and washed with cold water until the pH of the filtrate becomes neutral. Then the crude solid was washed with hot water until colorless filtrate was observed. The crude solid was boiled in ethyl acetate (700 ml) for 2-3 hrs. The reaction mass was cooled and the suspension was filtered off and dried to yield 2-n-propyl-4-methyl-6-(l-methylbenzimidazol-2-yl)-lH- benzimidazole (V) (80 gms, Yield : 82 %).

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 4-Methyl-2-propyl-1H-benzo[d]imidazole-6-carboxylic acid.

Reference:
Patent; OGENE SYSTEMS (I) PVT LTD; LAKKOJU, Chakrapani; KONETI, Naga Raju; KOKKALLA, Sridhar; MALLELA, Sambhu Prasad Sarma; BOYAPATI, Nanoranjan Choudary; WO2012/28925; (2012); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1003-21-0, 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.

Example 5; N1-(3-Fluoro-4-(2-(1-methyl-1H-imidazol-5-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-phenylmalonamide (5e) Step 1: 7-Chloro-2-(1-methyl-1H-imidazol-5-yl)thieno[3,2-b]pyridine (16); Nitrogen was bubbled through a mixture of the tin derivative 6 (7.19 g, 15.7 mmol) and 5-bromo-1-methyl-1H-imidazole (2.02 g, 12.5 mmol) [a) Begtrup, M.; Larsen, P.; Acta Chem. Scand. 44, 10; 1990; 1050-1057. b) Begtrup, M.; Bull. Soc. Chim. Belz.; 97; 8-9; 1988; 573-598. c) Begtrup, M.; Larsen, P.: Chem. Pharm. Bull. 42, 9; 1994; 1784-1790.] in toluene (20 mL) for 5 minutes. Pd(PPh3)4 (1.50 g, 1.30 mmol) was added and nitrogen was bubbled for additional 5 minutes. Finally, the mixture was refluxed under nitrogen overnight, the resultant yellow suspension was concentrated under reduced pressure and then purified with flash chromatography (eluent EtOAc/MeOH 90:10), to afford title compound 16 as a yellow solid (2.48 g, 79% yield). MS (m/z): 250.0(M+H).

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

Reference:
Patent; Methylgene, Inc.; US2007/4675; (2007); 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 15469-97-3 as follows. 15469-97-3

(i) (2R)-1-(benzyloxy)-3-(1-trityl-1H-imidazol-2-yl)-2-propanol In an argon atmosphere, n-butyllithium (1.6 M solution in hexane, 6.9 ml) was added drop by drop to a solution of 1-tritylimidazole (3.10 g) in THF (80 mL) under ice cooling. After stirring at the same temperature for 30 minutes, (R)-2-[(benzyloxy)methyl]oxirane (1.52 mL) was added. After stirring under ice cooling for 1.5 hours and at room temperature for 1 hour, water was added and the reaction mixture was extracted with ethyl acetate. The extract was washed with water and saline and dried over magnesium sulfate, after which it was concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: ethyl acetate-hexane 1:1) to yield the titled compound (1.402 g) as a pale-yellow oily substance. 1H-NMR (CDCl3) delta: 2.06 (2H, dd, J=2.8 Hz, 18.0 Hz), 3.08 (1H, dd, J=5.4 Hz, 9.8 Hz), 3.21 (1H, dd, J=5.4 Hz, 9.8 Hz), 3.55-3.7 (1H, m), 4.36 (2H, s), 6.73 (1H, d, J=1.4 Hz), 6.93 (1H, d, J=1.4 Hz), 7.0-7.4 (20H, m).

According to the analysis of related databases, 15469-97-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Naito, Kenichiro; Furuya, Shuichi; Tasaka, Akihiro; Ban, Toshikazu; US2004/138160; (2004); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

288-32-4, A common compound: 288-32-4, name is 1H-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.

EXAMPLE 1 68 g of imidazole are dissolved in 245 g of a 37% strength by weight aqueous formaldehyde solution, 28 g of potassium hydroxide are added to the solution, and the mixture is refluxed for 3 hours. 1.3 liters of 65% strength nitric acid are heated at the boil in a stirred flask equipped witb a 50 cm column having a reflux divider, a contact thermometer and a dropping funnel. The reaction mixture containing the oligohydroxymethylimidazole compounds is then added dropwise to the boiling nitric acid in the course of 1 hour, and the mixture boils under reflux with vigorous evolution of nitrous gases. 30 minutes after the dropwise addition is complete, the evolution of these gases ceases. About 500 g of a 5-8% strength nitric acid are distilled off in the course of from 5 to 6 hours at from 100 to 102 C. and with a reflux ratio of 10:1. The reaction mixture is cooled in an ice bath, and the precipitated crystals are filtered off under suction, washed with 150 ml of water and dried. 50 g of imidazole-4,5-dicarboxylic acid having a purity of 96.6% (according to HPLC) and a melting point of 287-289 C. (decomposition) are obtained. The filtrate is cooled with ammonia water and thus neutralized, and is brought to pH 4 with formic acid.

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

Reference:
Patent; BASF Aktiengesellschaft; US4550176; (1985); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

The chemical industry reduces the impact on the environment during synthesis 705-09-9, name is 2-(Difluoromethyl)-1H-benzo[d]imidazole, I believe this compound will play a more active role in future production and life. 705-09-9

A mixture of 2-difluoromethyl-lH-benzimidazole (2.22 g), 2,4-dichloro- 6-morpholinopyrimidine (2.81 g), potassium carbonate (6.63 g) and DMF (50 ml) was stirred under nitrogen and heated to 900C for 16 hours. The resultant mixture was cooled, filtered and the filtrate was evaporated. The resultant product was purified by column chromatography on silica using increasingly polar mixtures of ethyl acetate in methylene chloride as eluent. The solid so obtained was washed with a 1 :1 mixture of isohexane and diethyl ether. There was thus obtained 4-chloro-2-(2-difluoromethylbenzimidazol- 1 -yl)-6-morpholinopyrirnidine (3.17 g); NMR Spectrum: (DMSOd6) 3.75 (s, 8H), 7.09 (s, IH), 7.45-7.47 (m, IH), 7.50-7.54 (m, IH), 7.57-7.83 (t, IH), 7.87 (d, IH), 8.31 (d, IH); Mass Spectrum: M+H1″ 366.

The chemical industry reduces the impact on the environment during synthesis 705-09-9. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BUTTERWORTH, Sam; GRIFFEN, Edward, Jolyon; PASS, Martin; WO2008/32086; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

104-98-3, A common heterocyclic compound, 104-98-3, name is 3-(1H-Imidazol-4-yl)acrylic acid, molecular formula is C6H6N2O2, 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.

Urocanic acid (32) (4.74 g, 34.33 mmol), amine 33 (5.5 g, 34.33 mmol) and HOBt (5.26 g, 34.33 mmol) were suspended/dissolved in DMF (50 mL) and the mixture was cooled to 0 C. N-(3-Dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (6.91 g, 36.05 mmol) was added and the mixture was slowly warmed to rt and stirred overnight (The suspension turned to a clear orange solution after 2 h). The mixture was diluted with 2.5% aq NaOH (500 mL) and brine (100 mL). Repeated treatment with EtOAc (12 * 200 mL) afforded an extraction of product 34 only in low amounts and extraction with CHCl3 (2 * 150 mL) failed as well. Therefore, the aqueous phase was concentrated under reduced pressure at 40 C to a volume of 300 mL and then treated twice with CHCl3/MeOH 5:1 (500 and 400 mL). The organic phases were combined with the earlier EtOAc and CHCl3 extracts and removal of the volatiles under reduced pressure yielded a yellow liquid (ca 50 mL). DMF was removed under reduced pressure (50 C, 10 mbar) and the residue was subjected to column chromatography (eluent: CH2Cl2/MeOH 50:1 to 10:1). Removal of the solvent from the eluate under reduced pressure, uptake in CH2Cl2 (80 mL), evaporation, uptake in CH2Cl2 (50 mL) followed by removal of the solvent in vacuo afforded 34 as a white powder (8.27 g, 86%), mp 159-161 C. A minor fraction was recrystallized from acetone/EtOAc to yield colorless needles, mp 165-167 C. Rf = 0.6 (CH2Cl2/MeOH 5:1). Anal. calcd for C13H20N4O3: C, 55.70; H, 7.19; N, 19.99; found: C, 55.65; H, 7.29; N, 19.86. IR (Nujol) 3355, 3300, 1685, 1665, 1630, 1530 cm-1. 1H NMR (400 MHz, CD3OD) delta (ppm) 1.46 (s, 9H), 3.23 (t, 2H, J 6.2 Hz), 3.39 (t, 2H, J 6.2 Hz), 6.52 (d, 1H, J 15.6 Hz), 7.36 (s, 1H), 7.46 (d, 1H, J 15.6 Hz), 7.77 (s, 1H). 13C NMR (100 MHz, CD3OD) delta (ppm) 29.6, 41.5, 42.0, 81.0, 120.1, 123.2 (br), 133.1, 137.5 (br), 139.2, 159.4, 170.2. MS (ESI, MeOH) m/z (%) 583 (76) [2M+Na]+, 319 (38) [M+K]+, 303 (100) [M+Na]+, 281 (17) [M+H]+, 203 (26) [M-C4H8-CO2+Na]+, 181 (22) [M-C4H8-CO2+H]+, C13H20N4O3 (280.32).

The synthetic route of 104-98-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Keller, Max; Traenkle, Christian; She, Xueke; Pegoli, Andrea; Bernhardt, Guenther; Buschauer, Armin; Read, Roger W.; Bioorganic and Medicinal Chemistry; vol. 23; 14; (2015); p. 3970 – 3990;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem