ethyl N-[(2-{[(4-{N'-[(hexyloxy)carbonyl]carbamimidoyl}phenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl]-N-pyridin-2-yl-beta-alaninate

Base Information

• Chemical Name: ethyl N-[(2-{[(4-{N'-[(hexyloxy)carbonyl]carbamimidoyl}phenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl]-N-pyridin-2-yl-beta-alaninate
• CAS No.: 211915-06-9
• Molecular Formula: C34H41N7O5
• Molecular Weight: 627.743
• Hs Code.: 2933990090
• Pharos Ligand ID: FLAWC2XFBW7X
• ChEMBL ID: CHEMBL539697
• Mol file: 211915-06-9.mol

Synonyms:BIBR-1048-BS-RS1;CHEBI:70746;ethyl N-[(2-{[(4-{N'-[(hexyloxy)carbonyl]carbamimidoyl}phenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl]-N-pyridin-2-yl-beta-alaninate;Dabigatran etexilate methanesulfonate;SCHEMBL505829;CHEMBL539697;Dabigatran etexilate (USAN/INN);BDBM50432209;s2154;STL450990;STL483396;D07144;AB01274780-01;AB01274780_02;A815191;3-[[[2-[[4-[(E)-amino-[hexoxy(oxo)methyl]iminomethyl]anilino]methyl]-1-methyl-5-benzimidazolyl]-oxomethyl]-(2-pyridinyl)amino]propanoic acid ethyl ester;ethyl 3-[[2-[[[4-[(E)-N'-hexoxycarbonylcarbamimidoyl]phenyl]amino]methyl]-1-methyl-benzimidazol-5-yl]carbonyl-pyridin-2-yl-amino]propanoate;ethyl N-[(2-{[(4-{N-[(hexyloxy)carbonyl]carbamimidoyl}phenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl]-N-pyridin-2-yl-beta-alaninate

Chemical Property of ethyl N-[(2-{[(4-{N'-[(hexyloxy)carbonyl]carbamimidoyl}phenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl]-N-pyridin-2-yl-beta-alaninate

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 1.49E-27mmHg at 25°C
• Melting Point: 128-129°
• Refractive Index: 1.614
• Boiling Point: 827.9 °C at 760 mmHg
• PKA: 9.88±0.46(Predicted)
• Flash Point: 454.5 °C
• PSA: 154.03000
• Density: 1.24 g/cm³
• LogP: 6.37590
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 5.7
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 17
• Exact Mass: 627.31691743
• Heavy Atom Count: 46
• Complexity: 1000

Purity/Quality:

99%min ^*data from raw suppliers

DabigatranEtexilate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCCCCCOC(=O)N=C(C1=CC=C(C=C1)NCC2=NC3=C(N2C)C=CC(=C3)C(=O)N(CCC(=O)OCC)C4=CC=CC=N4)N
• Isomeric SMILES: CCCCCCOC(=O)/N=C(\C1=CC=C(C=C1)NCC2=NC3=C(N2C)C=CC(=C3)C(=O)N(CCC(=O)OCC)C4=CC=CC=N4)/N
• Description: Dabigatran etexilate (Pradaxa, BIBR 1048, Boehringer Ingelheim) is the prodrug of dabigatran (originally known as BIBR 953), a potent, nonpeptidic small molecule that specifically and reversibly inhibits both free and clot-bound thrombin by binding to the active site of the thrombin molecule. Dabigatran etexilate is an orally administered pro-drug of dabigatran, which is a direct inhibitor of thrombin and a potent anticoagulant. The serine protease thrombin is the final mediator in the coagulation cascade that leads to the production of fibrin, the main protein component of blood clots. Thrombin is also a potent activator of platelets. Consequently, thrombin inhibitors have found utility as anticoagulants in treating arterial and venous thrombosis. Warfarin, although orally available, has a narrow therapeutic index and requires frequent monitoring and dosage adjustment. Low-molecular-weight heparins provide better safety profile and less inter-patient variability; however, these agents are only available for parenteral administration. Direct thrombin inhibitors (DTIs) are a new class of anticoagulants that act by directly binding to thrombin at its catalytic or fibrinogen-binding sites, or both. Unlike the heparins, DTIs do not require the activation of secondary factors such as antithrombin to derive their activity, which makes their action more predictable. In addition, their ability to inhibit both free and clot-bound thrombin predisposes them for enhanced anticoagulation effect.
• Uses: BIBR-1048 (Dabigatran) is an anticoagulant from the class of the direct thrombin inhibitors. It is being studied for various clinical indications and in many cases it offers an alternative to warfarin as the preferred orally administered blood thinner sin Dabigatran Etexilate is an oral anticoagulant and direct thrombin inhibitor.
• Clinical Use: #N/A
• Drug interactions: Potentially hazardous interactions with other drugs Analgesics: possible increased risk of bleeding with NSAID’s; increased risk of haemorrhage with ketorolac or IV diclofenac - avoid. Anti-arrhythmics: concentration increased by amiodarone, reduce dose of dabigatran; concentration increased by dronedarone - avoid. Antibacterials: concentration reduced by rifampicin - avoid; possibly increased risk of bleeding with clarithromycin. Anticoagulants: increased risk of haemorrhage with other anticoagulants - avoid. Antidepressants: possible increased risk of bleeding with SSRIs; concentration possibly reduced by St John’s wort - avoid. Antifungals: concentration increased by ketoconazole and possibly itraconazole - avoid Ciclosporin: concentration possibly increased by ciclosporin - avoid. Sulfinpyrazone: possible increased risk of bleeding. Tacolimus: concentration possibly increased by tacrolimus - avoid. Ticagrelor: concentration of dabigatran increased. Verapamil: reduce dose of dabigatran to 150 mg daily, 75 mg in GFR=30-50mL/min.

Technology Process of ethyl N-[(2-{[(4-{N'-[(hexyloxy)carbonyl]carbamimidoyl}phenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl]-N-pyridin-2-yl-beta-alaninate

There total 128 articles about ethyl N-[(2-{[(4-{N'-[(hexyloxy)carbonyl]carbamimidoyl}phenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl]-N-pyridin-2-yl-beta-alaninate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.4%

1-methyl-2-[N-(4-amidino-phenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid N-(2-pyridyl)-N-2-(ethoxycarbonylethyl)-amide p-toluenesulfonic acid salt (872728-85-3) + n-hexyl chloroformate (6092-54-2) → dabigatran etexilate (211915-06-9)

Guidance literature:

With potassium carbonate; In acetonitrile; at 0 ℃; Reagent/catalyst; Solvent; Temperature;

Reference yield: 88.94%

1-methyl-2-[N-(4-amidino-phenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid N-(2-pyridyl)-N-2-(ethoxycarbonylethyl)-amide p-toluenesulfonic acid salt (872728-85-3) + n-hexyl chloroformate (6092-54-2) → dabigatran etexilate (211915-06-9)

Guidance literature:

With triethylamine; In dichloromethane; at 10 - 20 ℃; Large scale;

Reference yield: 87.8%

N-[[2-(chloromethyl)-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridyl-β-alanine ethyl ester (1307233-94-8) + 4-aminobenzamidine-N-hexylcarbamate hydrochloride (1307233-93-7) → dabigatran etexilate (211915-06-9)

Guidance literature:

4-aminobenzamidine-N-hexylcarbamate hydrochloride; With sodium hydroxide; In acetic acid butyl ester; water; at 50 ℃;

N-[[2-(chloromethyl)-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridyl-β-alanine ethyl ester; With tetra-(n-butyl)ammonium iodide; sodium hydrogencarbonate; sodium iodide; In acetic acid butyl ester; cyclohexane; water; at 40 ℃; for 2h;

upstream raw materials:

n-hexyl chloroformate

4-methylamino-3-nitro-benzoic acid chloride

4-(methylamino)-3-nitrobenzoic acid

ethyl 3-{[{2-amino-1-(methylamino)phen-4-yl}carbonyl](pyridyn-2-yl)amino}propanoate

Downstream raw materials:

BIBR 1087

ethyl 3-[(2-{[4-(amino-hexyloxycarbonylimino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate maleic acid salt

3-[(2-{[4-(amino-hexyloxycarbonylimino-methyl)-phenyl-amino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate citric acid salt

ethyl-3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate salicylate

Refernces

• 1、 Sharif, Sd. Khasim,Ramudu, B. Sri,Nunna, Rambabu,Ramachandran. "An improved process for preparation of dabigatran etexilate mesylate". . p. 1253 - 1257. Retrieved 2017.
• 2、 -. "Benzenesulfonate and preparation method thereof, and application of benzenesulfonate in preparation of dabigatran etexilate". Paragraph 0077-0081. . Retrieved 2020/07/02.
• 3、 -. "Dabigatran etexilate mesylate preparation method". . . Retrieved 2019/07/04.