Month: August 2021

Reference of 870837-18-6, A common heterocyclic compound, 870837-18-6, name is 3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde, molecular formula is C12H12N2O2, 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.

Synthesis of (Z)-(6S,9aR)-6-(3,4-difluorophenyl)-3-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]hexahydropyrido[2,1-c][1,4]oxazin-4-one A solution of (4R,6S)-6-(3,4-difluorophenyl)-3-hydroxyhexahydropyrido[2,1-c][1,4]oxazin-4-one (151 mg) and triphenylphosphonium bromide (220 mg) in acetonitrile (7 mL) was heated under reflux for one hour and then left to cool to room temperature. To the reaction solution, 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde (115 mg) and triethylamine (0.22 mL) were added, and the reaction solution was stirred at room temperature for 12 hours. Ethyl acetate and saturated sodium bicarbonate water were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with brine, dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane:ethyl acetate=1:1->ethyl acetate) to obtain 150 mg of the title compound. The property values of the compound are as follows. ESI-MS; m/z 466[M++H]. 1H-NMR(CDCl3) delta (ppm): 1.38-1.58(m,2H), 1.66-1.80(m,2H), 2.10-2.28(m,2H), 2.30(s,3H), 3.85(s,3H), 4.03(t,J=10.4 Hz,1H), 4.05-4.16(m,1H), 4.35(dd,J=10.4,2.0 Hz,1H), 5.33(t,J=4.0 Hz,1H), 6.82(s,1H), 6.92(brs,1H), 6.98-7.02(m,1H), 7.04-7.16(m,2H), 7.20(d,J=8.0 Hz,1H), 7.35(d,J=2.0 Hz,1H), 7.36(dd,J=8.0,2.0 Hz,1H), 7.71(d,J=1.2 Hz,1H).

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; Eisai R&D Management Co., Ltd.; US2007/117798; (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 1003-21-0 as follows. SDS of cas: 1003-21-0

5-Bromo-1-methyl-1H-imidazole (6.66 g, 41.4 mmol) was added to a round bottom flask followed by tetrahydrofuran (150 mL) under an N2 atmosphere. The contents were cooled to 0 C. in an ice water bath. EtMgBr (3.0 M solution in THF, 13.3 mL, 39.8 mmol) was added slowly via syringe over approximately 5 minutes, then the ice bath was removed and the contents allowed to warm and stirred at room temperature for approximately 30 minutes. The vessel was then re-cooled to 0 C. and a solution of N-methoxy-N-methylpyrimidine-2-carboxamide (3.09 g, 15.9 mmol, Intermediate 66: step a) in THF (20 mL) was cannulated into the reaction vessel. The contents were allowed to stir at 0 C., then slowly warmed to room temperature, then heated to 40 C. in an oil bath for approximately 36 hours. The contents were then cooled to 0 C., quenched with a saturated aqueous NH4Cl solution, diluted with ethyl acetate and transferred to a separatory funnel. The aqueous layer was separated, extracted twice with EtOAc, then the combined organic phases were dried over MgSO4, filtered, then distilled under reduced pressure to yield an amber oil. The crude product was purified by flash column chromatography (silica gel, 0-10% DCM/(10% of a 2 M NH3 MeOH in DCM)) to provide the title compound.

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; US2015/105366; (2015); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 89830-98-8, The chemical industry reduces the impact on the environment during synthesis 89830-98-8, name is 5-Cyclopropyl-1H-imidazole, I believe this compound will play a more active role in future production and life.

[0357] To a solution of Example 18a (1.00 g, 3.67 mmol) in DMF (10 mL) were added Cul (351 mg, 1.83 mmol), Cs2C03 (2.38 g, 7.30mmol), Example 18b(476 mg, 4.41 mmol), andN1,N2-dimethyl- cyclohexane-l,2-diamine (105 mg, 0.74 mmol). The resulting mixture was degassed with N2 and stirred at 130°C under microwave for 2 h. The mixture was diluted with MeOH and filtered. The filtrate was concentrated under vacuum and the residue was purified byPrep-HPLC (by Ultimate XB-C18, 50 x 250 mm, 10 mum, speed: 80 mL/min, eluent: H20/CH3CN = from 80/20 to 20/80 over 50 min)to give the desired product Example 18c (110 mg, yield 12percent) as a yellow solid. LC-MS: [M+H]+ = 253.0

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-Cyclopropyl-1H-imidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; FRONTHERA U.S. PHARMACEUTICALS LLC; JIN, Bohan; DONG, Qing; HUNG, Gene; (227 pag.)WO2018/151830; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. 106429-59-8, name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde

Step 5.5-((7-(5-((5-fluoro-2′-(1-hydroxypropan-2-yl)-[1,1′-biphenyl]-2-yl)oxy) pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2-yl)methyl)-1H-benzo[d]imidazol-2(3H)-one (1143) (1144) To a suspension of 2-(2′-((4-(2,7-diazaspiro[4.4]nonan-2-yl)pyrimidin-5-yl)oxy)- 5′-fluoro-[1,1′-biphenyl]- 2-yl)propan-1-ol (20 mg, 0.45 mmol) and 2-oxo-2,3-dihydro- 1H-benzo[d]imidazole-5-carbaldehyde (Intermediate 40, 7.3 mg,0.045 mmol) in anhydrous MeOH (3 mL) was added NaBH3CN (5.8 mg, 0.09 mmol) under a nitrogen atmosphere and the mixture was stirred at 60-65 C for 16 h. An additional batch of 2- oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbaldehyde (10 mg, 0.062 mmol) and NaBH3CN (7 mg, 0.11 mmol) were added, the reaction mixture was stirred at 60-65 C for an additional 18 h. The reaction mixture was concentrated under reduced pressure and purified by RP-HPLC-method A to give 5-((7-(5-((5-fluoro-2′-(1-hydroxypropan-2-yl)- [1,1′-biphenyl]-2-yl)oxy)pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-2-yl)methyl)-1H- benzo[d]imidazol-2(3H)-one (TFA salt) as a white solid.Yield: 13 mg. LCMS method E: Rt = 1.752 min, (M+H)+ = 595.2 1H NMR (CD3OD): delta 8.45 (s, 1H), 7.74 (s, 1H), 7.07- 7.44 (m, 10 H), 4.35-4.50 (m, 2H), 3.40-3.95 (m, 9H), 3.10-3.25 (m, 1H), 2.75-2.85 (m, 1H), 1.95-2.20 (m, 4H), 1.00-1.25 (m, 3H).19F NMR (C MeOD): delta -117.47, -76.69 ~ – 77.90.

According to the analysis of related databases, 106429-59-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; VITAE PHARMACEUTICALS, INC.; CACATIAN, Salvacion; CLAREMON, David, A.; DILLARD, Lawrence, Wayne; DONG, Chengguo; FAN, Yi; JIA, Lanqi; LOTESTA, Stephen, D.; MARCUS, Andrew; MORALES-RAMOS, Angel; SINGH, Suresh, B.; VENKATRAMAN, Shankar; YUAN, Jing; ZHENG, Yajun; ZHUANG, Linghang; PARENT, Stephan, D.; HOUSTON, Travis, L.; (444 pag.)WO2017/214367; (2017); 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 150058-27-8 as follows. Safety of Methyl 2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

The 45g2-ethoxy -1H-benzimidazole-7-carboxylic acid and 500 ml by adding dichloromethane for added to a reaction flask, stirring cooling to 20 °C the following, to-drop 50.7g triethylamine, the drop finishes, drop by adding 54.0g to toluene sulfonyl chloride and 100 ml dichloromethane mixed solution, drop Bi Yu 10-20 °C stirring reaction 3h, for 10-20 °C adding 39.7g4-hydroxymethyl-5-methyl -1,3-dioxol-2-one, the temperature rising to adding 30-40 °C stirring reaction, with used in HPLC. After the reaction is complete, cooling to 15-25°C, by adding 400 ml purified water stirring, layered, with 30g drying by anhydrous sodium sulfate. Decompression jeung dry dichloromethane, by adding 300 ml methyl tert-butyl ether refined, cooling to 0-5 °C stirring crystallization 3h, filtering, with 20 ml cool to 0-5 °C methyl tert-butyl ether washing, for 40-50 °C reduced-pressure drying to the job (5-methyl-2-oxo -1,3-dioxol-4-yl) methyl 2-ethoxy -1H-benzo[d] imidazol-7-carboxylic acid ester 63.6 g. The yield of 91.6percent, purity 98.1percent

According to the analysis of related databases, 150058-27-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Long days Chongqing Pharmaceutical Co., Ltd; Meng, Wenxue; Long, Daobing; Chen, Shunxiang; (14 pag.)CN105622595; (2016); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 1243204-92-3, A common heterocyclic compound, 1243204-92-3, name is 3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)benzonitrile, molecular formula is C12H11N3O, 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.

b) Preparation of intermediate 2 and 2a. A stirred sol. of intermediate 1 (1.40 g, 6.57 mmol) in anhydrous EtOH (1.4 ml) and Et2O (28 ml) was cooled at 0 0C. HCl gas was bubbled through the contents for 20 min, then the ensuing r.m. left to stir overnight at r.t. The precipitated product was collected by filtration and dried to give the HCl salt of the desired product as an off-white solid. Yield: 1.72 g of intermediate 2 (78.9%). Intermediate 2 was used as such in the next reaction step, or was converted into the free base by dissolving it in water, basifying the solution via addition of Na2Ctheta3, and extraction of the resulting suspension with DCM. The organic layer was dried (MgSO4), filtered and cone, in vacuo to yield intermediate 2a (quantitative yield).

The synthetic route of 1243204-92-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ORTHO-MCNEIL-JANSSEN PHARMACEUTICALS, INC; WU, Tongfei; GIJSEN, Henricus, Jacobus, Maria; ROMBOUTS, Frederik, Jan, Rita; BISCHOFF, Francois, Paul; BERTHELOT, Didier, Jean-Claude; OEHLRICH, Daniel; DE CLEYN, Michel, Anna, Jozef; PIETERS, Serge, Maria, Aloysius; MINNE, Garrett, Berlond; VELTER, Adriana, Ingrid; VAN BRANDT, Sven, Franciscus, Anna; SURKYN, Michel; WO2011/6903; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 10597-52-1, A common heterocyclic compound, 10597-52-1, name is 7-Nitro-1H-benzo[d]imidazole, molecular formula is C7H5N3O2, 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.

4-Nitro-1-(3-nitrophenyl)benzimidazole was prepared analogueously to 3 g from 4-nitrobenzimidazole and 1-fluoro-3-nitrobenzene. Mp 260-262 C. 1-(3-Aminophenyl)-4-nitrobenzimidazole was prepared from 4-nitro-1-(3-nitrophenyl)benzimidazole as described in Example 3a. Mp 159-161 C.

The synthetic route of 10597-52-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NeuroSearch A/S; Meiji Seika Kaisha, Ltd.; US5554630; (1996); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 641571-13-3, These common heterocyclic compound, 641571-13-3, name is 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzoic 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.

Example 17; N- 3 -(2, 5 ‘-Bipyrimidin-4-ylamino”)-4-methylphenyll -3 -(4-methy 1- 1 iZ-imidazol- 1 -vD-5- (trifluoromethyDbenzamide; A solution of 3 -(4-methy 1- 1 H-imidazol- 1 -y l)-5 -(trifluoromethyl)benzoic acid (Method27; 100 mg5 0.36 mmol), N3-255’-bipyrimidin-4-yl-4-methylbenzene-l53-diamine (Method 20; 97 mg5 0.36 mmol) and DIEA (0.25 ml, 1.08 mmol) in DMF (5 ml) was treated with HATU (205 mg, 0.40 mmol). The reaction mixture was stirred for 15 h at 25 C. The reaction was quenched with 10% NaOH and extracted with EtOAc. The organics were dried with NaCl(sat) and then Na2SO4(S) and removed under reduced pressure. The residue was purified by reverse phase semi-preparative chromatography to give the title compound. NMR (300 MHz): 10.75 (s, IH)5 9.75 (s, IH), 9.45 (s, 2H)5 9.41 (s, IH), 9.21 (s, IH)5 8.66 (s, IH), 8.33 – 8.45 (m, 3H), 8.17 – 8.22 (m, 2H), 7.52 (d, IH), 7.27 (d, IH)5 6.73 (d, IH)5 2.31 (s, 3H)5 2.19 (s, 3H); m/z 531.

Statistics shows that 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzoic acid is playing an increasingly important role. we look forward to future research findings about 641571-13-3.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2006/79791; (2006); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 17228-38-5, name is N-Methyl-1H-benzo[d]imidazol-2-amine, 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 17228-38-5, name: N-Methyl-1H-benzo[d]imidazol-2-amine

(5R,8aS)-3-Chloro-1 -(1 -methanesulfonyl-1 -methyl-ethyl)-5-methyl-5,6,8a,9- tetrahydro-8H-7,1 0-dioxa-2,4,4b-triaza-phenanthrene (1 .85 g), benzimidazole2-yl-methylamine (719 mg), tris(dibenzylideneacetone)dipalladium(0) (895 mg; 0.2 eq.) and dicyclohexyl-(2?,4?,6?-triisopropyl-biphenyl-2-yl)-phosphane (932 mg) were dissolved in dioxane (10 ml), lithium tert-butoxide (1,0 M solution in tetrahydrofuran) (6.8 ml, 1.4 eq) was added and the mixture was stirred for 1 h at 80 00. The reaction mixture was purified by chromatography(dichloromethane I methanol) to afford {1 -[(5R,8aS)-1 -(1 -Methanesulfonyl-1 -methyl-ethyl )-5-methyl -5,6 ,8a ,9-tetrahyd ro-8 H-7, 1 0-d ioxa-2 ,4 ,4b-triaza-phenanthren-3-yl]-1 H-benzimidazol-2-yl}-methyl-amine as a yellow solid (1 .18g); LCMS (method E): 0.50 mm (purity 98%); [MH+] 473.3 mlz; 1H NMR (500MHz, DMSO-d6) 6 8.19 (q, J = 4.8 Hz, 1 H), 8.00 (d, J = 7.6 Hz, 1 H), 7.28 -7.21 (m, 1 H), 7.07 (td, J = 7.6, 1 .2 Hz, 1 H), 6.97 (td, J = 7.7, 1 .3 Hz, 1 H), 4.63 (qd, J = 6.8, 2.9 Hz, 1 H), 4.43 (dd, J = 11 .0, 3.4 Hz, 1 H), 4.04 – 3.94 (m, 2H),3.88 (d, J= 11.6 Hz, 1H), 3.83 (dd, J= 11.1,9.2Hz, 1H), 3.70 (dd, J 11.6,3.2 Hz, 1 H), 3.22 -3.15 (m, 1 H), 3.05-3.01 (m, 6H), 1.84 (5, 3H), 1.81(s, 3H), 1 .35 (d, J = 6.8 Hz, 3H)and (1 H-Benzimidazol-2-yl)-[(5R,8aS)-1 -(1 -methanesulfonyl-1 -methyl-ethyl)-5- methyl-5,6,8a,9-tetrahydro-8H-7, 1 0-dioxa-2,4,4b-triaza-phenanthren-3-yl]-methyl-amine as a beige solid (722 mg); LCMS (method E): 0.53 mm (purity94%);[MH+]473.3m/z; 1H NMR (400 MHz, DMSO-d6)o 12.40(s, 1H),7.45-7.38 (m, 1 H), 7.34 – 7.27 (m, 1 H), 7.11 – 7.00 (m, 2H), 4.67 (qd, J = 6.5, 2.7Hz, 1 H), 4.38 (dd, J = 11 .0, 3.5 Hz, 1 H), 3.99 – 3.89 (m, 2H), 3.82 (d, J = 11.5Hz, 1 H), 3.76 (dd, J = 11 .0, 8.8 Hz, 1 H), 3.72 (s, 3H), 3.65 (dd, J = 11.7, 3.3 Hz, 1H), 3.15 (t, J= 11.8 Hz, 1H), 3.04 (s, 3H), 1.83 (s, 3H), 1.81 (s, 3H), 1.29(d, J = 6.8 Hz, 3H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, N-Methyl-1H-benzo[d]imidazol-2-amine, and friends who are interested can also refer to it.

Reference:
Patent; MERCK PATENT GMBH; BURGDORF, Lars; DORSCH, Dieter; TSAKLAKIDIS, Christos; (189 pag.)WO2017/202748; (2017); 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. 16681-56-4, name is 2-Bromo-1H-imidazole, A new synthetic method of this compound is introduced below., COA of Formula: C3H3BrN2

Intermediate E-0 (13.6 g) was dissolved in 80 mL of NMP and compound 275-4 (6.5 g) and Na2C03 (4.6 g) were added. The solution was stirred at 90 C for 6 h, then NMP was removed under reduced pressure. The residue was dissolved in EtOAc, washed with water and purified by silica gel flash chromatography (PE: EA= 2: 1) to give compound 275-5 as a yellow oil.

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; ELAN PHARMACEUTICALS, INC.; NEITZ, R., Jeffrey; TROUNG, Anh, P.; GALEMMO, Robert, A.; YE, Xiaocong, Michael; SEALY, Jennifer; ADLER, Marc; BOWERS, Simeon; BEROZA, Paul; ANDERSON, John, P.; AUBELE, Danielle, L.; ARTIS, Dean, Richard; HOM, Roy, K.; ZHU, Yong-liang; WO2012/48129; (2012); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem