Author: Jessica.F

Related Products of 1003-21-0, 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 1003-21-0 as follows.

Example 14a: 4-((3-(4-(1H-1,2,4-triazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl)benzonitrile A solution of isopropylmagnesium chloride-lithium chloride complex in tetrahydrofuran (1.3 M, 0.986 mL, 1 ,28 mmol) was added dropwise to an ice-water cooled, stirring suspension of 5- bronio-1 -methyl- IH- imidazole (241 mg, 1.50 mmol) in dry tetrahydrofuran (6 mL). After 5 minutes, the flask was removed from the cooling bath and the white suspension was stirred at 23 C. After 10 minutes, the Grignard suspension was added to an ice-water cooled, stirring mixture containing 4-(3-(4-( IH- 1 ,2,4-triazol- 1 -yl)benzyl)-4-chloro-2-methoxyquinoline-6- carbonyl)benzonitrile (205 mg, 0.427 mmol, Intermediate 16: step e) and lanthanum(III) chloride bis(lithium chloride) complex (0.6 M solution in tetrahydrofuran, 1.42 mL, 0.854 mmol) in dry tetrahydrofuran (8 mL), After 20 minutes, 1 M aqueous citric acid solution (1 niL) was added. The flask was removed from, the cooling bath and then ethyl acetate (100 mL) was added. Additional 1 M aqueous citric acid solution (-15 mL) was added until the mixture was comprised of two homogeneous layers, at which point saturated aqueous sodium bicarbonate solution was added until the H of the aqueous layer was ~8 by litmus paper test. The layers were separated. The aqueous layer was extracted with ethyl acetate (20 mL). The organic layers were combined and the combined solution was dried over sodium sulfate. The dried solution was filtered. Silica gel (5 g) was added to the filtrate and the mixture was concentrated by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a silica gel column for flash-column chromatography purification. Elution with dichloromethane initially, grading to 50% methanol–dich.lorometh.ane provided the title compound as a w hite solid. H NMR (5001 MHz, CDCI3) delta ppm 8.45 (s, 1H), 8.10 (d . ./ 2.2 Hz, 1 I S). 8.0(S (s, U S). 7.81 (d, ,/ 8.8 Hz, 1H), 7.65 (d, J = 8.5 Hz, 2H), 7.58-7.51 (m, 5H), 7.44-7.38 (m, 3H), 6.41 (d, ,7 = 1.1 Hz, 1H), 4.33 (s, 2H), 4.09 (s, 3H), 3.94 (s, 1H), 3.38 (s, 3H); MS (ESI): mass calcd. C31H24CIN7O2, 561.2; m/z found, 562.1 [M+H]+.4-((3-(4-(l H-l ,2,4-Triazol-l-yl)benzyl)-4-chloro-2-methoxyquinolin-6lH-imidazol-5-yl)methyl)benzonitrile was purified by chiral SFC (Chiralpak AD-H column, 5 mupiiota, 250 mm. 20 mm, mobile phase: 60% C02, 40% methanol) to give two enantiomers. The first eluting enantiomer was Example 14b:3H NMR (500 MHz, CDCI3) delta ppm 8.44 (d, J = 1.0 Hz, 1H), 8.10 (d, J= 2.1 Hz, 1 H), 8.06 (s, 1 H), 7.81 (d, J= 8.7 Hz, 1H), 7.66 (d, J= 8.2 Hz, 2H), 7.58-7.50 (m, 5H), 7.44-7.38 (m, 3H), 6.42 (s, 1H), 4.33 (s, 2H), 4,09 (s, 3H), 4.02-3.81 (br s, 1 H), 3.38 (s, 3H); MS (ESI): mass calcd. C31H24CIN7O2, 561.2; m/z found, 562.3 [M+H]+ and the second eluting enantiomer was Example 14c: H NMR (500 MHz, CDCI3) delta ppm. 8.45 (s, I I I). 8.09 (d, J —— 2.2 Hz, 1 H), 8.06 (s, IH), 7.85 (d, ./ 8.9 Hz, 1H), 7.66 (d, ./ = 8.1 Hz, 21 1).7.58-7.51 (m, 5H), 7.45-7.38 (m, 3H), 6.43 (s, 5 H), 4.33 (s, 2H), 4.09 (s, 3H), 3.38 (s, 3H); MS (ESI): mass calcd. C31H24CIN7O2, 561 .2; m/z found, 562.3 [M+H]+.

According to the analysis of related databases, 1003-21-0, the application of this compound in the production field has become more and more popular.

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.; JONES, William Moore; GOLDBERG, Steven; WO2015/57205; (2015); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 17325-26-7, These common heterocyclic compound, 17325-26-7, name is 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.

a) Methyl 2-isopropyl- lH-imidazole-4-carboxylateA solution of methyl lH-imidazole-4-carboxylate (5.0 g, 39.68 mmol), AgN03 (4.0 g, 23.81 mmol), isobutyric acid (10.4 g, 1 19.1 mmol) in 10 % H2S04 (150 ml) was heated at 80 C for 15 min. An aqueous solution of (NH4)2S208 (28.0 g, 119.1 mmol) was added to the mixture dropwise in 15 minat 80 C. The reaction mixture was cooled to RT and poured into ice. The mixture was basified with aqueous ammonia (pH 9) and extracted with EtOAc (500 ml). The organic layer was concentrated and the residue was purified by flash chromatography. Yield 1.5 g. 1H- NMR (400 MHz; CDC13): delta 1.36 (d, 6H), 3.05-3.14 (m, 1H), 3.87 (s, 3H), 7.62 (s, 1H).

The synthetic route of 17325-26-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ORION CORPORATION; TOeRMAeKANGAS, Olli; WOHLFAHRT, Gerd; SALO, Harri; RAMASUBRAMANIAN, Rathna, Durga; PATRA, Pranab, Kumar; MARTIN, Arputharaj, Ebenezer; HEIKKINEN, Terhi; VESALAINEN, Anniina; MOILANEN, Anu; KARJALAINEN, Arja; WO2012/143599; (2012); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 28890-99-5, A common heterocyclic compound, 28890-99-5, name is 5H-Benzo[d]benzo[4,5]imidazo[1,2-a]imidazole, molecular formula is C13H9N3, 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.

Compound 4-1 (3 g, 5.8 mmol), benzimidazolo[1,2-a]benzimidazole (1.26 g, 6.1 mmol), and potassium phosphate (2.58 g, 12.2 mmol) were suspended in NMP (29 mL). The mixture was stirred at 190 Cfor48 h. After the reaction mixture was cooled at room temperature, 58 mL of EtCH and 29 mL of water were added to the reaction mixture to give a solid. Itwas collected by filtration, and it was purifed by column chromatography on silica gel eluting with a mixed solvent of toluene and CHCI3. Then, the product was recrystallized with toluene and heptane. The formed solid was collected by filtration and dried in vacuum to yield 2.39 g (59%) of compound (B-25) as a white solid. LC-MS (mlz) 704.1HNMR (300 MHz, DMSC-d6): 68.39-8.36 (m, 2H), 8.15-8.12 (m,1H), 8.01-7.72 (m, 9H),7.61-7.25 (m, 13H), 7.01(d, J= 1.4 Hz, 1H), 7.54 (td, J= 7.5, 1.2 Hz, 1H), 6.57 (td, J= 7.5,1.2 Hz, 1H)

The synthetic route of 28890-99-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; IDEMITSU KOSAN CO., LTD.; NISHIMAE, Yuichi; KOHLSTEDT, Julia; SCHAeFER, Thomas; NAGASHIMA, Hideaki; (114 pag.)WO2016/97983; (2016); 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 75370-65-9 as follows. Safety of 4-Amino-1H-benzo[d]imidazol-2(3H)-one

Amine 2a (1.3 g, 5.9 mmol) was dissolved in 40 ml of AcOEt and at 0C triphosgene (1.75 g, 5.9 mmol) was added to the solution. The mixture was warmed at 80C for 4 hours then evaporated and the residue was dissolved in 5ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound la (860 mg, 5.77 mmol) and the mixture was warmed at 80C for 8 hours. (TLC AcOEt). The solvent was evaporated and the crude was dissolved in AcOEt (50 ml) and washed with water (1 X 30 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 650mg of a yellow solid. Yield = 28% ‘HNMR (DMSO, 200 MHz) delta 2.51 (6H, bs), 4.43 (2H, d, J = 5.6 Hz), 6.62 (1H, dd, J = 7.6 Hz, J’ = 1 Hz), 6.82 (2H, m), 6.97 (1H, dd, J = 8 Hz, J’ = 1 Hz), 7.32 (1H, s), 7.39 (1H, d), 7.49 (1H, d), 8.35 (1H, bs), 9.99 (1H, bs), 10.59 (1H, bs); [M+1] 394.1 (C18H18F3N5O2 requires 393.36).

According to the analysis of related databases, 75370-65-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PHARMESTE S.R.L.; NAPOLETANO, Mauro; TREVISANI, Marcello; PAVANI, Maria Giovanna; FRUTTAROLO, Francesca; WO2011/120604; (2011); 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. 918321-20-7, name is Methyl 5-amino-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylate, A new synthetic method of this compound is introduced below., Quality Control of Methyl 5-amino-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylate

A mixture of Xantphos (1.20 g, 2.05 mmol) and tris(dibenzylideneacetone)dipalladium (0) (1.26 g, 1.37 mmol) in anhydrous anisole (76 mL) was stirred under nitrogen, at 50 0C for 30 minutes to provide a an orange- brown solution of the catalyst.[00326] To a stirred mixture of 6-amino-7-fluoro-3-methyl-3H-benzoimidazole-5- carboxylic acid methyl ester (6) (8.00 g, 34.16 mmol) and cesium carbonate (22.48 g, 68.31 mmol) in anhydrous anisole (76 mL) under nitrogen was added 4-bromo-2- chloroiodobenzene (1.60 g, 1.10 equiv., 4.88 mmol). The preformed catalyst, as prepared above, was then added to the mixture to provide a dark brown suspension, which was heated at 100 +/- 2 0C, with stirring at 350 rpm. The reaction was monitored by HPLC analysis. After 41 hours, no 6-amino-7-fluoro-3-methyl-3//-benzoimidazole-5-carboxylic acid methyl ester (6) remained. The reaction mixture was cooled to about 80 0C and IM sulfuric acid (40.99 mL 40.99 mmol) was added. Gas evolution was observed after 10 minutes and the rate of addition was controlled to moderate the effervescence. At the end of the addition the pH was between 7 and 8. Additional sulfuric acid (IM, 10.25 mL, 10.25 mmol) was then added to give mobile slurry with a pH of 0. The mixture was diluted with anisole (20 mL) and Celatom FW- 14 filter agent was added. It was then filtered at about 80 C through a water-wet pad of Celatom FW- 14 filter agent and the cake was washed with anisole (1 x 40 mL + 3 x 20 mL), then water (10 mL). The lower aqueous layer was separated and discarded and the organic layer was washed with 10 % aqueous NaCl solution (2 x 40 mL). This was added to a sodium hydroxide (5.46 g, 68.3 mmol) in methanol (24 mL) and the mixture was heated at 65 C with stirring. After 17.5 hours HPLC analysis indicated that the hydrolysis of the ester was complete and the slurry was cooled to 15 C, then filtered on a sinter. The solid was washed with water (4 x 24 mL), MTBE (24 mL), and acetonitrile (2 x 25 mL) and then dried at 45 0C in a vacuum oven to provide 11.07 g of 6-(4- EPO bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (7) as a fine pale brown solid (assay 93.7% by 1H NMR), actual wt 10.37 g (72.2% yield). 1H NMR (400 MHz, d6 DMSO) delta 3.85 (3H, s, NMe), 6.53 (IH, dd, J 9, 7, Ar-H), 7.27 (IH, dd, J 9S 2.5, Ar-H), 7.56 (IH, d, J 9, Ar-H), 7.97 (IH, s, Ar-H), 8.20 (IH5 s, Ar-H), 11.5 (IH, s, CO2H). 13C NMR (100 MHz, d6 DMSO) delta 31 (CH3), 108 (CH, d, J 2), 109 (CH), 117 (C, d, J6), 122 (C), 124 (C, d, J7), 127 (C)5 130 (C)5 131 (C), 132 (C, d, J9), 133 (C5 d, J l l), 141 (C), 145 (CF, d5 J 252), 146 (CH)5 170 (C=O).

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; ARRAY BIOPHARMA INC.; ASTRAZENECA AB; WO2007/2157; (2007); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 615-16-7, The chemical industry reduces the impact on the environment during synthesis 615-16-7, name is 2-Hydroxybenzimidazole, I believe this compound will play a more active role in future production and life.

Step 1: (0389) 1H-benzimidazol-2(3H)-one 19-a (500 mg, 3.73 mmol) was added into anhydrous aluminum chloride (1.98 g, 14.9 mmol) and tetrachloroethane (3 ml). Chloroacetyl chloride (843 mg, 7.46 mmol) dissolved in tetrachloroethane (3 ml) was added dropwise thereto under ice bath followed by stirring at 100 C. for 1 hour. The mixture was cooled to room temperature, ice and 4N hydrochloric acid (20 ml) were added sequentially followed by stirring for 6 hours, the precipitated solid was filtered, the filter cake was slurried in isopropanol, filtered, and dried to give 19-b as an off-white solid (730 mg, yield: 93%). EI-MS (m/z): 210.

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

Reference:
Patent; SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES; SUZHOU VIGONVITA LIFE SCIENCES CO., LTD.; TOPHARMAN SHANDONG CO., LTD.; JIANG, Hualiang; WANG, Zhen; LI, Jianfeng; ZHANG, Rongxia; HE, Yang; LIU, Yongjian; BI, Minghao; LIU, Zheng; TIAN, Guanghui; CHEN, Weiming; YANG, Feipu; WU, Chunhui; WANG, Yu; JIANG, Xiangrui; YIN, Jingjing; WANG, Guan; SHEN, Jingshan; (70 pag.)US2017/158680; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 570-22-9, A common heterocyclic compound, 570-22-9, name is 1H-Imidazole-4,5-dicarboxylic acid, molecular formula is C5H4N2O4, 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.

General procedure: The complex was synthesized by hydrothermal method. A mixture of Zn(NO3)2.6H2O (0.47 g; 1.6 mmol), H3idc (0.25 g, 1.6 mmol) and water (30 mL) was sealed in a 45 mL Parr brand teflon-linedacid digestion bomb and heated at 180 C for 5 days, and then cooled to room temperature at a rate of 5 C/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:
Article; Erer, Hakan; Ye?ilel, Okan Zafer; ?ahin, Onur; Bueyuekguengoer, Orhan; Inorganica Chimica Acta; vol. 434; (2015); p. 14 – 23;,
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. 288-32-4, name is 1H-Imidazole, A new synthetic method of this compound is introduced below., Recommanded Product: 1H-Imidazole

Take 7kg sodium hydride DMF solution with 20% concentration, add 7kg 20% imidazole DMF solution under ice-cooling at a speed of 2ml/s with stirring, stir at 60C for 60min; use ice salt After the bath is cooled, 5 kg of 1-chloro-4-(4-chlorophenyl)-2-butanol is slowly added, and the reaction is stirred at 60 C. for 120 min. After cooling with an ice bath, the reaction solution is obtained; in the reaction 25% by weight of n-hexane was added to the solution, stirred for 15 minutes at 3 revolutions per second, and then added to the solution.35 wt% of ice water was stirred at 3 rev/s until the precipitation stopped. After filtration, the cake was washed once with water 1/3 times the weight of the cake, and dried at 2825 r/min. After 60 minutes, ethyl acetate and activated charcoal were used 2.5 times and 0.05 times the weight of the centrifugally dried product, respectively, and allowed to stand at -5 C. for 13 hours to recrystallize, and the recrystallized product was dried at 50 C., ie, 1-(2-Hydroxy-4-(4-chlorophenyl)butyl)-1H-imidazole, purity99.31%.

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; Zhuzhou Qianjin Pharmaceutical Co., Ltd.; Li Sanxin; Peng Kaifeng; Ling Yonggen; Wen Fengqiu; Gong Yun; Li Fujun; (13 pag.)CN105198818; (2018); B;,
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. 50995-95-4, name is 2-Propylimidazole, A new synthetic method of this compound is introduced below., Safety of 2-Propylimidazole

Add 2,4-dichloropyrimidine (3.000 g, 20.2 mmol), 2-propylimidazole (2.662 g, 24.2 mmol) and potassium carbonate (4.168 g, 30.3 mmol)Add it to a round bottom flask (100 mL), using acetonitrile (40 mL) as a solvent,The reaction was carried out at 50 C for 11 hours. TLC was followed until the reaction was complete,Cooled to room temperature, distilled under reduced pressure,Purification by column chromatography to obtain white solid intermediate III-7(1.453 g), yield: 32.4%.

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; Southwest University; Zhou Chenghe; Wang Ya; Li Ruixue; Wang Jie; Geng Rongxia; (21 pag.)CN110452224; (2019); A;,
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 17228-38-5 as follows. Safety of N-Methyl-1H-benzo[d]imidazol-2-amine

Example 2.03 can also be prepared as follows:(3R)-4-(2-Chloro-6-(1-((R)-S-methylsulfonimidoyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine (179 mg, 0.54 mmol), N-methyl-1H-benzo[d]imidazol-2-amine (159 mg, 1.08 mmol) and cesium carbonate (529 mg, 1.62 mmol) were suspended in DMA (2 ml) and sealed into a microwave tube. The reaction mixture was heated to 80 C. for 90 minutes in a microwave reactor and then cooled to RT. The reaction mixture was filtered and then purified by preparative HPLC, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to afford a solid (55.0 mg). In an additional procedure: (R)-4-(2-Chloro-6-(1-((R)-S-methylsulfonimidoyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine (89 mg, 0.27 mmol), N-methyl-1H-benzo[d]imidazol-2-amine (79 mg, 0.54 mmol) and cesium carbonate (263 mg, 0.81 mmol) were suspended in DMA (2 ml) and sealed into a microwave tube. The reaction mixture was heated to 80 C. for 5 hours in a microwave reactor and then cooled to RT. The reaction mixture was filtered, and combined with the solid from the previous procedure and then purified by preparative HPLC using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated and the residue was purified by preparative HPLC using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated and the residue purified again by preparative HPLC using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to afford the title compound (38.4 mg, 32%); 1H NMR (400 MHz, DMSO-d6) 1.29 (3H, d), 1.52 (3H, m), 1.72-1.86 (1H, m), 3.02 (3H, s), 3.03 (3H, d), 3.26-3.33 (1H, m), 3.52 (1H, t), 3.66 (1H, d), 3.80 (1H, d), 4.01 (2H, m), 4.12 (1H, s, obscured by methanol peak), 4.51 (1H, s), 6.77 (1H, s), 6.98 (1H, t), 7.09 (1H, t), 7.25 (1H, d), 8.08 (1H, d), 8.71 (1H, d); m/z: (ES+) MH+, 442.16. Chiral HPLC: (HP1100 System 4, 20 mum Chiralpak AS (250 mm×4.6 mm) column eluting with iso-Hexane/IPA/TEA 70/30/0.1) Rf, 11.984 97.9%.

According to the analysis of related databases, 17228-38-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; US2011/306613; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem