Category: 46006-36-4

Application of 46006-36-4, 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 46006-36-4 as follows.

3H-Benzoimidazole-4-carboxylic acid[3-(1H-tetrazol-5-yl)-phenyl]-amide (16) 3-(1H-Tetrazol-5-yl)aniline (75 mg, 0.47 mmol), 1H-benzimidazole-4-carboxylic acid (76 mg, 0.47 mmol), 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (135 mg, 0.7 mmol), 1-hydroxybenzotriazole (95 mg, 0.7 mmol) and N,N’-diisopropylethylamine (0.17 mL, 0.94 mmol) was stirred in DMF (0.5 mL) at room temperature for 24 h. The reaction mixture is diluted with water (2 mL) and after approximately adjusting the pH to 4 with 1N HCl, the mixture was extracted with ethyl acetate. The organic extracts were washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The crude material was purified by reverse phase HPLC to afford the product as a trifluoroacetic acid salt in 5% yield. 1H NMR (DMSO-d6) delta 8.62 (s, 1H), 8.53 (s, 1H), 7.99-8.02 (m, 3H), 7.86 (d, J=8 Hz, 1H), 7.77 (d, J=4 Hz, 1H), 7.62 (t, J=8 Hz, 1H), 7.43 (t, J=8 Hz, 1H), 7.04 (s, 1H); LCMS (ESI) m/z 306 (MH+).

According to the analysis of related databases, 46006-36-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; UNIVERSITY OF SOUTH FLORIDA; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; Chen, Yu; Nichols, Derek; Renslo, Adam R.; Jaishankar, Priyadarshini; Lauterwasser, Erica M. W.; (29 pag.)US9556131; (2017); B2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. 46006-36-4, name is 1H-Benzimidazole-7-carboxylic acid belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. SDS of cas: 46006-36-4

Example 144 : N-(5-((5-(4-(dimethylcarbamoyl)phenyl)pyridin-2-yl)amino)pyridin-3- yl)-1H-benzo[d]imidazole-4-carboxamide. [0711] To a mixture of 4-(6-((5-aminopyridin-3-yl)amino)pyridin-3-yl)-N,N- dimethylbenzamide (80 mg, 0.24 mmol) in pyridine (2 mL) was added lH-benzo[d]imidazole-4-carboxybc acid (58 mg, 0.36 mmol) and EDOHC1 (92 mg, 0.48 mmol), the reaction mixture was stirred at 50 C for 2 h to give a brown suspension. LCMS (Rt = 0.660 min; MS Calc’d: 477.2; MS Found: 478.1 [M+H]+). The mixture was concentrated under reduced pressure to give a residue. The residue was purified by washing with MeOH (5 mL) to give a crude product. Then further purified by prep-HPLC (0.225% FA as an additive) to give N-(5-((5-(4- (dimethylcarbamoyl)phenyl)pyridin-2-yl)amino)pyridin-3-yl)-1H-benzo[d]imidazole-4- carboxamide (7.9 mg, yield: 7%) as a white solid. LCMS (Agilent LCMS 1200-6140 A, mobile phase: from 99% [water + 0.1% FA] and 1% [MeCN + 0.1% FA] to 95% [water + 0.1% FA] and 5% [MeCN + 0.1% FA] in 0.6 min, then changed to 100% [MeCN + 0.1% FA] under this condition for 3.4 min, finally back to 99% [water + 0.1% FA] and 1 % [MeCN + 0.1% FA] and under this condition for 0.5 min.) purity is 97.48%, Rt = 2.126 min; MS Calc’d: 477.2; MS Found: 478.3 [M+H]+. NMR (400 MHz, DMSO-rie) d 2.91-3.05 (6H, m), 7.04 (1H, d, J = 8.8 Hz), 7.45-7.53 (3H, m), 7.76 (2H, d, J = 8.4 Hz), 7.85-7.94 (1H, m), 8.00-8.07 (2H, m), 8.61-8.72 (3H, m), 8.74-8.80 (1H, m), 8.83-8.92 (1H, m), 9.75 (1H, br s).

The synthetic route of 46006-36-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PETRA PHARMA CORPORATION; LINDSTROeM, Johan; PERSSON, Lars Boukharta; VIKLUND, Jenny; KESICKI, Edward A.; HICKEY, Eugene R.; DAHLGREN, Markus K.; GERASYUTO, Aleksey I.; (450 pag.)WO2019/126731; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 46006-36-4, name is 1H-Benzimidazole-7-carboxylic acid, molecular formula is C8H6N2O2, 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. SDS of cas: 46006-36-4

Step 1: (lH-Benzo[d]imidazol-4-yl)(l-methyl-lH-spiro[chromeno[4,3- c] pyrazole-4,4 ‘-piperidine] -1 ‘-yl)methanone To a solution of l-methylspiro[chromeno[4,3-c]pyrazole-4,4′-piperidine] (211 mg, 0.830 mmol), lH-benzimidazole-4-carboxylic acid (134 mg, 0.830 mmol) and triethylamine (346 mu?, 2.50 mmol) in dichloromethane (2 mL) was added HATU (314 mg, 0.830 mmol) in one portion and the mixture was stirred for 12 hours. The reaction mixture was treated with 1M NaOH (1 mL) for 10 minutes. Dichloromethane (5 mL) was added. The two layers were separated and the aqueous layer was extracted with dichloromethane (2 5 mL). The organic layers were combined, washed with brine, dried over MgS04, filtered and evaporated to yield a residue that was purified on silica using a gradient of 0.5-30% MeOH in dichloromethane to yield (1 H-benzo[d]imidazol-4-yl)(l -methyl- 1 H-spiro[chromeno[4,3-c]pyrazole-4,4’- piperidine]- -yl)methanone. ESI-MS m/z calc. 399.5, found 400.5 (M+l)+. Retention time: 1.12 minutes (4 min run).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 46006-36-4, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; HADIDA-RUAH, Sara, Sabina; GROOTENHUIS, Peter, Diederik, Jan; MILLER, Mark, Thomas; ANDERSON, Corey; PONTILLO, Joseph; KALLEL, Edward, Adam; NUMA, Mehdi, Michael, Djamel; FRIEMAN, Bryan, A.; McCARTNEY, Jason; WORLEY, Jennings, Franklin; ARUMUGAM, Vijayalaksmi; UY, Johnny; HILGRAF, Nicole; BEAR, Brian, Richard; WO2013/67248; (2013); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 46006-36-4, name is 1H-Benzimidazole-7-carboxylic acid, 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 46006-36-4, Formula: C8H6N2O2

B. (lH-Benzo[d]imidazol-4-yI)methanol.; lH-Benzo[d]imidazole-4- carboxylic acid (1.04 g, 6.41 mmol) was suspended in anhydrous tetrahydrofuran (80 mL) and cooled to -78 0C. A solution of lithium aluminum hydride in tetrahydrofuran (2.0M, 6.4 mL) was added via syringe. The reaction was allowed to warm to room temperature and stirred overnight. The reaction was quenched with methanol and adsorbed onto silica gel. Flash chromatography (20% MeOH in EtOAc) afforded a white solid (550 mg, 3.72 mmol, 58%). MS (ESI) m/z 149.0 [M+l]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1H-Benzimidazole-7-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; SIGNAL PHARMACEUTICALS, LLC; WO2008/51494; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 46006-36-4, name is 1H-Benzimidazole-7-carboxylic acid, 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 46006-36-4, Formula: C8H6N2O2

B. (lH-Benzo[d]imidazol-4-yI)methanol.; lH-Benzo[d]imidazole-4- carboxylic acid (1.04 g, 6.41 mmol) was suspended in anhydrous tetrahydrofuran (80 mL) and cooled to -78 0C. A solution of lithium aluminum hydride in tetrahydrofuran (2.0M, 6.4 mL) was added via syringe. The reaction was allowed to warm to room temperature and stirred overnight. The reaction was quenched with methanol and adsorbed onto silica gel. Flash chromatography (20% MeOH in EtOAc) afforded a white solid (550 mg, 3.72 mmol, 58%). MS (ESI) m/z 149.0 [M+l]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1H-Benzimidazole-7-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; SIGNAL PHARMACEUTICALS, LLC; WO2008/51494; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 46006-36-4, name is 1H-Benzimidazole-7-carboxylic acid, molecular formula is C8H6N2O2, 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. HPLC of Formula: C8H6N2O2

General procedure: A solution of 6-chloronicotinic acid (2.0 g, 0.012 mole) in DMF (5 mL) was added to a suspension of sodium hydride (0.76 g, 0.015 mole) in DMF (3 mL) under N2 at 25 C and stirred for 1 hour. Methyl iodide (1.5 mL, 0.025 mole) was added at RT and warmed to 50 C for 2 hours. Reaction mixture was cooled to RT, quenched in to ice cold water (50 mL) and extracted with ethyl acetate (50 mL x 3). Organic layer was washed with brine solution (50 mL), dried over Na2SC>4 and concentrated under vacuum to obtain methyl 6-chloronicotinate. Yield: 1.6 g; Mass (m/z): 172.0, 174.0 (M+H) +.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 46006-36-4, its application will become more common.

Reference:
Patent; SUVEN LIFE SCIENCES LIMITED; NIROGI, Ramakrishna; SHINDE, Anil Karbhari; MOHAMMED, Abdul Rasheed; BADANGE, Rajesh Kumar; JAYARAJAN, Pradeep; BHYRAPUNENI, Gopinadh; JASTI, Venkateswarlu; (172 pag.)WO2018/42362; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 46006-36-4, 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 46006-36-4 as follows.

3H-Benzoimidazole-4-carboxylic acid[3-(1H-tetrazol-5-yl)-phenyl]-amide (16) 3-(1H-Tetrazol-5-yl)aniline (75 mg, 0.47 mmol), 1H-benzimidazole-4-carboxylic acid (76 mg, 0.47 mmol), 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (135 mg, 0.7 mmol), 1-hydroxybenzotriazole (95 mg, 0.7 mmol) and N,N’-diisopropylethylamine (0.17 mL, 0.94 mmol) was stirred in DMF (0.5 mL) at room temperature for 24 h. The reaction mixture is diluted with water (2 mL) and after approximately adjusting the pH to 4 with 1N HCl, the mixture was extracted with ethyl acetate. The organic extracts were washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The crude material was purified by reverse phase HPLC to afford the product as a trifluoroacetic acid salt in 5% yield. 1H NMR (DMSO-d6) delta 8.62 (s, 1H), 8.53 (s, 1H), 7.99-8.02 (m, 3H), 7.86 (d, J=8 Hz, 1H), 7.77 (d, J=4 Hz, 1H), 7.62 (t, J=8 Hz, 1H), 7.43 (t, J=8 Hz, 1H), 7.04 (s, 1H); LCMS (ESI) m/z 306 (MH+).

According to the analysis of related databases, 46006-36-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; UNIVERSITY OF SOUTH FLORIDA; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; Chen, Yu; Nichols, Derek; Renslo, Adam R.; Jaishankar, Priyadarshini; Lauterwasser, Erica M. W.; (29 pag.)US9556131; (2017); B2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. 46006-36-4, name is 1H-Benzimidazole-7-carboxylic acid belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. Safety of 1H-Benzimidazole-7-carboxylic acid

Example 144 : N-(5-((5-(4-(dimethylcarbamoyl)phenyl)pyridin-2-yl)amino)pyridin-3- yl)-1H-benzo[d]imidazole-4-carboxamide. [0711] To a mixture of 4-(6-((5-aminopyridin-3-yl)amino)pyridin-3-yl)-N,N- dimethylbenzamide (80 mg, 0.24 mmol) in pyridine (2 mL) was added lH-benzo[d]imidazole-4-carboxybc acid (58 mg, 0.36 mmol) and EDOHC1 (92 mg, 0.48 mmol), the reaction mixture was stirred at 50 C for 2 h to give a brown suspension. LCMS (Rt = 0.660 min; MS Calc’d: 477.2; MS Found: 478.1 [M+H]+). The mixture was concentrated under reduced pressure to give a residue. The residue was purified by washing with MeOH (5 mL) to give a crude product. Then further purified by prep-HPLC (0.225% FA as an additive) to give N-(5-((5-(4- (dimethylcarbamoyl)phenyl)pyridin-2-yl)amino)pyridin-3-yl)-1H-benzo[d]imidazole-4- carboxamide (7.9 mg, yield: 7%) as a white solid. LCMS (Agilent LCMS 1200-6140 A, mobile phase: from 99% [water + 0.1% FA] and 1% [MeCN + 0.1% FA] to 95% [water + 0.1% FA] and 5% [MeCN + 0.1% FA] in 0.6 min, then changed to 100% [MeCN + 0.1% FA] under this condition for 3.4 min, finally back to 99% [water + 0.1% FA] and 1 % [MeCN + 0.1% FA] and under this condition for 0.5 min.) purity is 97.48%, Rt = 2.126 min; MS Calc’d: 477.2; MS Found: 478.3 [M+H]+. NMR (400 MHz, DMSO-rie) d 2.91-3.05 (6H, m), 7.04 (1H, d, J = 8.8 Hz), 7.45-7.53 (3H, m), 7.76 (2H, d, J = 8.4 Hz), 7.85-7.94 (1H, m), 8.00-8.07 (2H, m), 8.61-8.72 (3H, m), 8.74-8.80 (1H, m), 8.83-8.92 (1H, m), 9.75 (1H, br s).

The synthetic route of 46006-36-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PETRA PHARMA CORPORATION; LINDSTROeM, Johan; PERSSON, Lars Boukharta; VIKLUND, Jenny; KESICKI, Edward A.; HICKEY, Eugene R.; DAHLGREN, Markus K.; GERASYUTO, Aleksey I.; (450 pag.)WO2019/126731; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 46006-36-4,Some common heterocyclic compound, 46006-36-4, name is 1H-Benzimidazole-7-carboxylic acid, molecular formula is C8H6N2O2, 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 94N-CCls^sJ^-Cl-CS’-CCCSS^RJ-S^-dimethylpiperazin-l-yOmethyO^’-hydroxybiphenyl-S- yloxy)-5-fluoronicotinamido)cyclohexyl)-lH-benzo[d]imidazole-4-carboxamide To a solution of N-((ls,4s)-4-aminocyclohexyl)-2-(3′-(((3S,5R)-3,5-dimethylpiperazin-l- yl)methyl)-4′-hydroxybiphenyl-3-yloxy)-5-fluoronicotinamide (100 mg, 0.17 mmol) in dry DMF (5 mL) under nitrogen was added DIPEA (0.057 mL, 0.34 mmol) at RT. The solution was stirred until homogeneous. To this solution was added dropwise a solution of IH- benzo[d]imidazole-4-carboxylic acid (27.8 mg, 0.17 mmol) and l,l’-carbonyldiimidazole (27.8 mg, 0.17 mmol) in dry DMF (5 mL) under nitrogen which had been allowed to stir at 40 0C for 1 h. The reaction mixture was allowed to stir at 50 0C overnight. The mixture was evaporated to dryness and the residue dissolved in chloroform (15 mL) and washed with saturated NaHCO3 (aq), water, dried (MgSO4) and evaporated to give a yellow oil. This was purified by preparative HPLC to afford the title compound. Yield: 36.5 mg 1H NMR (400 MHz, CD3OD) delta 8.69 (s, IH), 8.49 (d, J= 6.9 Hz, IH), 8.12 – 8.07 (m, 2H), 7.91 (d, J= 7.7 Hz, IH), 7.84 (d, J= 8.2 Hz, IH), 7.52 – 7.41 (m, 6H), 7.38 (s, IH), 7.16 – 7.10 (m, IH), 6.87 (d, J= 8.5 Hz, IH), 4.21 – 4.09 (m, 2H), 4.07 (s, 2H), 3.62 – 3.49 (m, 2H), 3.41 (d, J= 12.8 Hz, 2H), 2.65 (t, J= 12.4 Hz, 2H), 1.99 – 1.74 (m, 8H), 1.30 (d, J= 6.7 Hz, 6H). MS: [M+H]+=692.3 (calc=692.336) (MultiMode+)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1H-Benzimidazole-7-carboxylic acid, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2009/144494; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 46006-36-4, name is 1H-Benzimidazole-7-carboxylic acid, molecular formula is C8H6N2O2, 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. Safety of 1H-Benzimidazole-7-carboxylic acid

Step 1: ethyl 1H-benzimidazole-4-carboxylate 2.50 g (15.4 mmol) 1H-benzimidazole-4-carboxylic acid in 100 mL ethanol are combined with 50 mL saturated ethanolic hydrochloric acid solution and refluxed for 15 hours. The reaction mixture is poured into saturated, aqueous potassium carbonate solution and extracted with ethyl acetate. The combined organic phases are dried on sodium sulphate and evaporated down to 50 mL using the rotary evaporator and filtered. 1.80 g (9.46 mmol, 61%) ethyl 1H-benzimidazole-4-carboxylate are obtained as a colourless solid. Rf=0.92 [silica gel, dichloromethane/methanol (80/20)] MS [ESI (M+H)+]]=191

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 46006-36-4, its application will become more common.