Month: September 2021

Synthetic Route of 616-47-7,Some common heterocyclic compound, 616-47-7, name is 1-Methyl-1H-imidazole, molecular formula is C4H6N2, 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.

Triethylamine (3.40 mL, 24.4 mmol) and Ethyl chloroformate (2.34 mL, 24.4 mmol) were added at 0 C. to an acetonitrile (4.0 mL) solution of 1-methyl-1H-imidazole (1.00 g, 12.2 mmol), and the reaction solution was stirred at room temperature for 16 hours. The reaction solution was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, hexane/ethyl acetate), thereby obtaining ethyl 1-methyl-1H-imidazole-2-carboxylate (1.50 g, 9.73 mmol, 80%) as a white solid.1H-NMR (400 MHz, CDCl3) delta: 1.42 (3H, t, J=7.2 Hz), 4.01 (3H, s), 4.40 (2H, q, J=7.2 Hz), 7.01-7.03 (1H, m), 7.13-7.15 (1H, m)ESI-MS: m/z=155 (M+H)+

The synthetic route of 616-47-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Toray Industries, Inc.; Takahashi, Hirozumi; Baba, Yoko; Morita, Yasuhiro; Iseki, Katsuhiko; Izumimoto, Naoki; (19 pag.)US2020/172507; (2020); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 3012-80-4, 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 3012-80-4 as follows.

A solution of 1-methyl-2-formylbenzimidazole (1 g) in methanol (27 mL) and acetic acid (0.54 mL) was treated with aminoacetaldehyde diethylacetal (0.9 g, 1 equivalent) and NaCNBH3 (0.85 g, 2 equivalents) at 25° C., stirred for 1 hour. The mixture was partitioned between water and ethyl acetate. The organic layer was separated, washed sequentially with saturated NaHCO3 and brine, and concentrated. The residue was chromatographed on silica gel, eluting with 8percent methanol/dichloromethane to give 1.2 g (64percent) of the title compound.

According to the analysis of related databases, 3012-80-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Flentge, Charles A.; Chen, Hui-Ju; DeGoey, David A.; Flosi, William J.; Grampovnik, David J.; Huang, Peggy P.; Kempf, Dale J.; Klein, Larry L.; Krueger, Allan C.; Madigan, Darold L.; Randolph, John T.; Sun, Minghua; Yeung, Ming C.; Zhao, Chen; US2005/131042; (2005); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 3543-74-6, These common heterocyclic compound, 3543-74-6, name is Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, 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 Bendamustine Hydrochloride (Crude) (0099) Step 1: 4-{5-[Bis-(2-hydroxy-ethyl)-amino]-1-methyl-1H-benzoimidazol-2-yl}-butyric acid ethyl ester (27.0 kg) was dissolved in 270 kg chloroform. After cooling to 0 to 5 C., 19.2 kg thionyl chloride was added over about 1 hour. The mixture was warmed to 25 C.±5 C. and stirred for 20 to 24 hours. 75.6 kg hydrochloric acid (32% aqueous solution) was then added. After phase separation, the organic (lower) phase was removed. The product remained in the aqueous phase. (0100) Step 2: A suspension of activated charcoal in hydrochloric acid was added to the aqueous phase obtained in step 1. The mixture was heated over 1 hour to 85 to 90 C. and stirred for 4 to 5 hours at reflux. The suspension was then filtered and rinsed with aqueous hydrochloric acid. The solvent was distilled off under reduced pressure at a temperature not exceeding 65 C. 108 kg to 324 kg (108 kg preferred) of warm (35 to 45 C.) deionized water was added to induce crystallization. (0101) After crystallization, the mixture was cooled to 20 C±5 C. and stirred for an additional 1 to 2 hours or overnight. The product was collected by filtration on a filter dryer, washed with three portions each of 108 to 324 kg (108 kg preferred) deionized water and 108 to 216 kg (108 kg preferred) of cold acetone. The crude product was treated four times each with 54 to 108 kg (54 kg preferred) acetone at reflux for at least 1 hour, in the filter dryer. The suspension was filtered and the product dried at a temperature not higher than 40 C. under reduced pressure, to give 21.4 kg±2.1 kg bendamustine hydrochloride crude (70%±10%, calculated as dried substance). (0102) Step 3 (optional): The product obtained from step 2 was dissolved in hydrochloric acid (32% aqueous solution) and heated to reflux (85 to 90 C.) for at least 4 hours. To improve color, activated charcoal can be added to the hydrochloric acid and the mixture heated to reflux (85 to 90 C.) for at least 4 hours. With activated charcoal, the suspension was filtered and rinsed with aqueous hydrochloric acid. Solvent was distilled off under reduced pressure at a temperature not exceeding 65 C. The mixture was then diluted with deionized water. If no crystallization occurred within 15 min, the mixture was seeded. After crystallization, the suspension was stirred at 40 C.±5 C. for one hour, then cooled to 20 C.±5 C. After stirring an additional 1 to 2 hours at 20 C.±5 C., the product was collected by filtration, washed three times with cold deionized water, and at least three times with cold acetone. The crude product was treated four times with acetone at reflux for at least 1 hour. The suspension was filtered and the product dried at a temperature not higher than 40 C., under reduced pressure. Yield was of crude bendamustine hydrochloride was 80%±10%. Preparation of Purified Bendamustine Hydrochloride (0103) Bendamustine HCl crude (15.0 kg) was suspended with 0.45 kg activated charcoal in ethanol/water (vol/vol=97/3) at room temperature. The mixture was quickly warmed to 75 to 80 C. and stirred for not more than 10 min under reflux conditions. The mixture was filtered to remove the activated charcoal. After filtration, 33.0 kg of filtered acetone was added quickly at 40-50 C. to induce crystallization. (0104) After crystallization, the mixture was stirred for 30 to 60 min at 40-50 C., then cooled to 0 to 5 C., and stirred for at least an additional 30 min or overnight. The product was collected by filtration and washed with three 45 kg of cold acetone. After that, the crude product was treated 4 times each with 30 kg acetone at reflux for at least 1 hour. The suspension was filtered and the product dried at a temperature not higher than 40 C. under reduced pressure providing 11.3±1.5 kg bendamustine hydrochloride (75%±10%).

The synthetic route of 3543-74-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Cephalon, Inc.; Cooper, Martin Ian; Courvoisier, Laurent D.; Eddleston, Mark; McKean, Robert E.; (31 pag.)US2016/159748; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 1848-84-6, These common heterocyclic compound, 1848-84-6, name is 2-Ethyl-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.

A mixture of 2- { 1 -[2-chloro-9-methyl-6-((5)-3-methylmorpholin-4-yl)-9H- purin-8-ylmethyl]piperidin-4-yl}propan-2-ol (200 mg, 0.47 mmol), 2-ethylbenzimidazole (73 mg, 0.50 mmol), tris(dibenzylideneacetone)dipalladium (12 mg, 2.5 molpercent), XPhos (20 mg, 10 molpercent) and Cs2CO3 (218 mg, 0.67 mmol) in DMF (6 mL) was purged with argon then heated at 150 0C for 1 h in a microwave reactor. The reaction mixture was loaded onto an Isolute.(R). SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NEta3/MeOEta. The resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 0-5percent) then (Si-PCC, MeOH:DCM, 0-3percent) affording 775 (95 mg, 38percent). LCMS (method I): Rx 2.65 min, [M+H]+ 533.3. 1H NMR (CDCl3, 400 MHz): delta 8.03-8.02 (1 H, m), 7.75-7.74 (1 H, m), 7.27-7.24 (2 H, m), 5.40 (2 H, brd s), 4.09-4.03 (1 H, m), 3.88 (3 H, s), 3.83 (2 H, s), 3.75-3.55 (4 H, m), 3.36 (2 H, q, J = 7.48 Hz), 2.98-2.95 (2 H, m), 2.11 (2 H, t, J = 10.92 Hz), 1.81-1.71 (2 H, m), 1.45-1.44 (6 H, m), 1.34-1.31 (4 H, m), 1.19 (6 H, s)

Statistics shows that 2-Ethyl-1H-benzo[d]imidazole is playing an increasingly important role. we look forward to future research findings about 1848-84-6.

Reference:
Patent; GENENTECH, INC.; F. HOFFMANN-LA ROCHE AG; CASTANEDO, Georgette; CHAN, Bryan; GOLDSTEIN, David Michael; KONDRU, Rama K.; LUCAS, Matthew C.; PALMER, Wylie Solang; PRICE, Stephen; SAFINA, Brian; SAVY, Pascal Pierre Alexandre; SEWARD, Eileen Mary; SUTHERLIN, Daniel P.; SWEENEY, Zachary Kevin; WO2010/138589; (2010); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 570-22-9, These common heterocyclic compound, 570-22-9, name is 1H-Imidazole-4,5-dicarboxylic 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.

In H2O (12ml) solvent, was added CuBr (0.121g, 0.85mmol), 2,2′- bipyridine (0.086g, 0.5mmol), 4,5-imidazole acid (0.078g, 0.5mmol), NaOH (0.020 g, 0.5mmol), placed on a magnetic stirrer was stirred for 30 minutes, the reaction was placed in 25ml teflon-lined autoclave, sealed in a high temperature oven, constant-temperature 160 C for five days to 5 C / h rate down to room temperature, a blue precipitate in the reactor bulk crystal, in 60% yield (based on copper).

Statistics shows that 1H-Imidazole-4,5-dicarboxylic acid is playing an increasingly important role. we look forward to future research findings about 570-22-9.

Reference:
Patent; Capital Normal University; Lu, Xiaoming; Cheng, Yifeng; (14 pag.)CN103965224; (2016); B;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 93-84-5, 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. 93-84-5, name is 5-Nitro-1H-benzo[d]imidazol-2(3H)-one belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

a 1,3-dimethyl-5-nitro-1,3-dihydrobenzimidazol-2-one 90 parts of 5-nitro-1,3-dihydrobenzimidazol-2-one are suspended in 500 parts of aqueous sodium hydroxide solution (30%) and the suspension is heated to 53 C.; 161 parts of dimethyl sulphate are added dropwise over 12 hours during which the temperature rises to 70 C. The mixture is cooled to room temperature and filtered and the solid product is washed to neutrality. Drying under reduced pressure at 80 C. gives 99 parts of a beige powder of a compound of the following formula Yield: 96% Melting point: 206.3 C. 1H-NMR (DMSO): delta: 3.35 (s, CH3)-3.37 (s,CH3)-7.28 (d, 3J=9 Hz, H-C7)-7.98 (d, 4J=2 Hz, H-C4)-8.00 (dd, 3J=9 Hz, 4J=2Hz, H-C6)

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-Nitro-1H-benzo[d]imidazol-2(3H)-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Clariant Finance (BVI) Limited; US6255482; (2001); B1;,
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 10040-98-9 as follows. SDS of cas: 10040-98-9

General procedure: A mixture of azolyl ketone (1a/1b) (1 mmol) and aryloxy benzaldehyde (2a-f) (1 mmol) were dissolved in 10% NaOH-EtOH (5 mL), it was stirred at room temperature for 9-10 h. After completion, 5 mL water was added to the reaction mixture. The separated solid compound was filtered and washed with water. It was purified by crystallization with methanol/chloroform or basic alumina column chromatography to give the desired compounds (3-13).The compounds (16-31) were prepared by the reaction of their corresponding aldehyde and ketone partners.

According to the analysis of related databases, 10040-98-9, the application of this compound in the production field has become more and more popular.

Reference:
Article; Marrapu, Vijay K.; Chaturvedi, Vinita; Singh, Shubhra; Singh, Shyam; Sinha, Sudhir; Bhandari, Kalpana; European Journal of Medicinal Chemistry; vol. 46; 9; (2011); p. 4302 – 4310;,
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 33468-67-6 as follows. Recommanded Product: 33468-67-6

Example 40 Synthesis of l-[l-(4-chlorophenyl)-5-isopropylpyrazol-4-yl]-3-[2-methyl-4- (trifluoromethyl)imidazol-l-yl]pyrrolidin-2-one [0200] A mixture of 3-bromo-l-[l-(4-chlorophenyl)-5-isopropylpyrazol-4-yl]pyrrolidin-2- one (0.110 g, 0.29 mmol), 2-methyl-4-(trifluoromethyl)-lH-imidazole (0.080 g, 0.53 mmol) and K2C03 (0.080 g, 0.58 mmol) in DMF (1.8 mL) was stirred at 65 C for 2 hrs. The mixture was then cooled to room temperature, quenched with water (30 mL), extracted with EtOAc (50 mL), and purified by reverse phase HPLC (CI 8 column, acetonitrile-H20 with 0.1% TFA as eluent) to yield the title compound (0.035 g, TFA salt, 21%). XH NMR (TFA salt) (400 MHz, CDC13) delta 7.58 (s, 1 H), 7.49 (m, 2 H), 7.35 (m, 2 H), 7.27 (s, 1 H), 5.03 (dd, J= 10.4, 8.8 Hz, 1 H), 3.89 (m, 1 H), 3.81 (m, 1 H), 3.04 (heptet, J= 6.8 Hz, 1 H), 2.88 (m, 1 H), 2.58 (s, 3 H), 2.40 (m, 1 H), 1.23 (m, 6 H); MS: (ES) m/z calculated for C2iH21ClF3 50 [M + H]+ 452.1, found 452.1.

According to the analysis of related databases, 33468-67-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CHEMOCENTRYX, INC.; CHEN, Xi; FAN, Pingchen; LI, Yandong; POWERS, Jay P.; MALATHONG, Viengkham; PUNNA, Sreenivas; TANAKA, Hiroko; ZHANG, Penglie; WO2014/89495; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 2302-25-2,Some common heterocyclic compound, 2302-25-2, name is 4-Bromo-1H-imidazole, molecular formula is C3H3BrN2, 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.

-Bromo- lH-imidazole(3.2 g, 21.8 mmol) was weighed into a 500 mL round bottomed flask equipped with a magnetic stir bar under a nitrogen atmosphere. Anhydrous DMF, (12 mL) was added and the mixture was placed on ice. After 10 min the mixture was treated with NaH (0.840 g, 21.0 mmol. 60% dispersion in oil). After 5 min, the ice bath was removed and the reaction was warmed to room temperature. After 15 min of vigorous stirring the ice bath was replaced and 3-(4-cyanophenyl)oxaziridine-2-carboxylic acid tert-butyl ester (1.92 g, 7.80 mmol) was added. The reaction was vigorously stirred for 5 min and the ice bath was removed. After 5 min the mixture was diluted with saturated NaHCC>3 and extracted with EtOAc. The organics were washed with dilute sodium carbonate, dried over Na2SC>4, filtered, and concentrated. The residue was purified using silica gel chromatography (0-5% MeOH / DCM) to afford the title compound (1.16 g, 4.43 mmol, 57 %) as a yellow oil: ]H NMR (400 MHz, CDCI3) delta 9.22 (s, 1H), 7.36 (d, / = 1.5 Hz, 1H), 6.97 (d, / = 1.5 Hz, 1H), 1.48 (s, 9H); ESIMS m/z 262 ([M]+), 260 ([M-2]”).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Bromo-1H-imidazole, its application will become more common.

Reference:
Patent; DOW AGROSCIENCES LLC; GARIZI, Negar; TRULLINGER, Tony K.; HUNTER, Ricky; ZHANG, Yu; NIYAZ, Noormohamed M.; KNUEPPEL, Daniel; LOWE, Christian T.; BUYSSE, Ann M.; WO2013/62980; (2013); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 144690-33-5, These common heterocyclic compound, 144690-33-5, name is Ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-((2′-(1-trityl-1H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylate, 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.

Formula 1Of ethyl 4- (2-hydroxypropan-2-yl)-2-Propyl-1-((2 ‘- (1-trityl-1H-tetrazol-5-yl) biphenyl-4-yl) methyl) -1H- imidazole-5-carboxylate was added a mixed solvent of purified water and dioxane Lithium hydroxide was added and reacted at room temperature for 2 hours. After confirming the termination of the reaction by thin-layer chromatography, the organic solvent was removed by concentration under reduced pressure, methylene chloride was added and neutralized with 1 N hydrochloric acid solution. The organic layer was separated, dried and concentrated, 2 4-(2-hydroxypropan-2-yl)-2-propyl-1 – ((2 ‘- (1-trityl-1H-tetrazol-5-yl)Biphenyl-4-yl) methyl)-1H-imidazole-5-carboxylate was synthesized

Statistics shows that Ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-((2′-(1-trityl-1H-tetrazol-5-yl)-[1,1’-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylate is playing an increasingly important role. we look forward to future research findings about 144690-33-5.

Reference:
Patent; DAEBONG LS, LTD; PARK, JIN-HO; KIM, YONG-GIL; KWON, JI-WONG; KIM, EUN-MI; LEE, JI-EUN; PARK, SEOK-YONG; (7 pag.)KR101696851; (2017); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem