Month: November 2020

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

33543-78-1, 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. 33543-78-1, name is Ethyl 1H-imidazole-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

Example 92 A mixture of 4-[4-(4-chlorophenyl)-2-(2-methyl-1-imidazolyl)-5-oxazolyl]butyl methanesulfonate(600 mg), ethyl 2-imidazolecarboxylate(410 mg), potassium carbonate(405 mg) and N,N-dimethylformamide (30 ml) was stirred for 2 hours at 80-90¡ã C. Water was added to the reaction mixture. This was extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried (Mg SO4). The residue obtained by evaporating the solvent was subjected to silica gel column chromatography. From the fraction eluted with acetone-hexane (1:1, v/v), obtained was ethyl 1-[4-[4-(4-chlorophenyl)-2-(2-methyl-1-imidazolyl)-5-oxazolyl]butyl)-2-imidazolecarboxylate as crystals (460 mg, 69percent). This was recrystallized from acetone-isopropyl ether to give colorless prisms. mp 134-135¡ã C.

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; Takeda Chemical Industries, Ltd.; US6177452; (2001); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

7098-07-9, These common heterocyclic compound, 7098-07-9, name is 1-Ethyl-1H-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.

(Reference Example 6) Synthesis of 1-ethyl-1H-imidazole-2-carbaldehyde: A solution of n-butyllithium in n-hexane (1.6 M, 7.15 mL, 11.4 mmol) was added dropwise to a solution of 1-ethyl-1H-imidazole (1.00 g, 10.4 mmol) in tetrahydrofuran (26 mL) at -78¡ãC and the reaction liquid was stirred at the same temperature for 1 hour. N,N-dimethylformamide (2.42 mL, 31.2 mmol) was added to the reaction liquid at the same temperature, and the reaction liquid was stirred for 1 hour, and then, the temperature of the reaction liquid was raised to room temperature. A saturated aqueous solution of ammonium chloride was added to the reaction liquid and then the reaction liquid was extracted with ethyl acetate. The organic layer was washed with a 10percent 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, hexane/ethyl acetate) to obtain 1-ethyl-1H-imidazole-2-carbaldehyde (1.12 g, 9.02 mmol, 87percent) as a yellow oil. 1H-NMR (400 MHz, CDCl3) delta: 1.44 (3H, t, J=7.6 Hz), 4.45 (2H, q, J=7.6 Hz), 7.18 (1H, s), 7.28 (1H, d, J=1.6 Hz), 9.82 (1H, s).

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 7098-07-9.

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

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. 3273-68-5, name is 4-(2-Oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)butanoic acid, A new synthetic method of this compound is introduced below., 3273-68-5

Part A. Preparation of chloro 2,3-dihydro-2-oxo-lH-benzimidazol-l- butanoate.4-(2-oxo-2,3- chloro 2,3-dihydro-2-oxo- dihydrobenzimidazol-l-yl)butyric acid lH-benzimidazol-1-butanoate4-(2-Oxo-2,3-dihydrobenzimidazol-l-yl)butyric acid (50 g; 0.227 mol), N ,N- dimethylformamide (1.84 g; 0.025 mol; 0.11 eq), and dichloromethane (480 g; 5,652 mol; 24.89 eq) were charged to a stirred-tank reactor. Oxalyl chloride (31.12 g; 0.245 mol; 1.08 eq) was then dosed at 10-200C over a 1-hour period while stirring. The resulting mixture was then stirred at 10-200C for an additional hour. All the above steps were conducted under a N2 atmosphere.; Part A. Preparation of chloro 2,3-dihydro-2-oxo-lH-benzimidazol-l- butanoate.4-(2-oxo-2,3- chloro 2,3-dihydro-2-oxo- dihydrobenzimidazol-l-yl)butyric acid lH-benzimidazol-1-butanoateDichloromethane (3772 L) and then 4-(2-oxo-2,3-dihydrobenzimidazol-l-yl)butyric acid (525 kg; 2.4 kmol) were charged to a stirred-tank reactor, followed by N5N- dimethylformamide (21 L). The resulting mixture was cooled to 1O0C. Afterward, oxalyl chloride (326.8 kg)) was dosed at 10-150C over 2-3 hours while stirring. The resulting mixture was then stirred at 15-2O0C for an additional 1-3 hours. All the above steps were conducted under a N2 atmosphere. Conversion was checked by in-process control (“IPC”).

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; INTERVET INTERNATIONAL B.V.; WO2008/119754; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem