Rivaroxaban

Base Information

• Chemical Name: Rivaroxaban
• CAS No.: 366789-02-8
• Molecular Formula: C19H18ClN3O5S
• Molecular Weight: 435.888
• European Community (EC) Number: 685-132-2
• UNII: 9NDF7JZ4M3
• DSSTox Substance ID: DTXSID3057723
• Nikkaji Number: J2.395.184C
• Wikipedia: Rivaroxaban
• Wikidata: Q420262
• NCI Thesaurus Code: C77995
• RXCUI: 1114195
• Pharos Ligand ID: RTBWU7W8TR7W
• Metabolomics Workbench ID: 65095
• ChEMBL ID: CHEMBL198362
• Mol file: 366789-02-8.mol

Synonyms:5-chloro-N-(((5S)-2-oxo-3-(4-(3-oxomorpholin-4-yl)phenyl)-1,3-oxazolidin-5-yl)methyl)thiophene-2-carboxamide;BAY 59 7939;BAY 59-7939;BAY 597939;rivaroxaban;xarelto

Chemical Property of Rivaroxaban

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 228-229°C
• Refractive Index: 1.633
• Boiling Point: 732.609 °C at 760 mmHg
• PKA: 13.36±0.46(Predicted)
• Flash Point: 396.868 °C
• PSA: 116.42000
• Density: 1.46 g/cm³
• LogP: 3.04080
• Storage Temp.: Refrigerator
• Solubility.: insoluble in H2O; insoluble in EtOH; ≥13.9 mg/mL in DMSO with gentle warming
• XLogP3: 2.5
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 435.0655696
• Heavy Atom Count: 29
• Complexity: 645

Purity/Quality:

99% HPLC ^*data from raw suppliers

Rivaroxaban ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antithrombotic Agents
• Canonical SMILES: C1COCC(=O)N1C2=CC=C(C=C2)N3CC(OC3=O)CNC(=O)C4=CC=C(S4)Cl
• Isomeric SMILES: C1COCC(=O)N1C2=CC=C(C=C2)N3C[C@@H](OC3=O)CNC(=O)C4=CC=C(S4)Cl
• Recent ClinicalTrials: Study to Gather Information About the Safety of Oral Anticoagulation Drugs and How Well These Drugs Work in Real World for Patients With Non-valvular Atrial Fibrillation (Irregularly Heart Beats Which is Not Caused by a Heart Valve Problem)
• Recent EU Clinical Trials: Anticoagulation for New-Onset Post-Operative Atrial Fibrillation after CABG
• Recent NIPH Clinical Trials: Optimal Duration of Anticoagulation Therapy for Low-risk Pulmonary Embolism Patients with Cancer
• Efficacy and Safety in Patients with Atrial Fibrillation and Bioprosthetic Mitral Valve: The Rivaroxaban for Valvular Heart Disease and Atrial Fibrillation (RIVER) trial demonstrated that rivaroxaban was noninferior to warfarin in patients with atrial fibrillation and a bioprosthetic mitral valve, with respect to the primary outcome of death, major cardiovascular events.
• Peripheral Artery Disease after Revascularization: In patients with peripheral artery disease who underwent lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a lower incidence of composite cardiovascular outcomes compared to aspirin alone. However, there was a higher incidence of bleeding with rivaroxaban and aspirin.
• Reduction in Myocardial Infarction Risk: A meta-analysis of large randomized clinical trials revealed a reduced risk for myocardial infarction (MI) in patients receiving rivaroxaban compared to different comparators. This reduction in MI risk was primarily observed in patient populations at high risk for ischemic coronary events.
• Inhibition of FXa-Driven Platelet Activation: Rivaroxaban reduces arterial thrombus stability by inhibiting factor Xa (FXa)-driven platelet activation via protease-activated receptor-1 (PAR-1). This mechanism was demonstrated in both in vivo and in vitro studies.
• Treatment of Cerebral Venous Thrombosis (CVT): Rivaroxaban holds promise for the treatment of cerebral venous thrombosis, with optimal modified Rankin Scale (mRS) scores and recanalization observed in patients treated with rivaroxaban compared to warfarin.
• Oral Anticoagulant: Rivaroxaban is an oral anticoagulant and the first available orally active direct inhibitor of factor Xa.

Technology Process of Rivaroxaban

There total 180 articles about Rivaroxaban 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: 97.0%

(S)-N-/3-{N-[4-(3-oxomorpholine-4-yl)phenyl]-N-(ethoxycarbonyl)amino}-2-hydroxyprop-1-yl/-5-chlorothiophene-2-carboxamide → Rivaroxaban (366789-02-8,865479-71-6)

Guidance literature:

With potassium carbonate; In methanol; at 20 ℃; for 2h;

DOI:10.1016/j.tetlet.2018.11.067

Reference yield: 96.0%

5-chlorothiophene-2-carbonyl chloride (42518-98-9) + 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one methanesulfonic acid salt (1251952-62-1) → Rivaroxaban (366789-02-8,865479-71-6)

Guidance literature:

With potassium hydrogencarbonate; In ethanol; water; butanone; at 20 - 35 ℃; for 0.75h; Large scale;

DOI:10.1080/00304948.2020.1741300

Reference yield: 95.6%

5-chlorothiophene-2-carbonyl chloride (42518-98-9) + 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one hydrochloride → Rivaroxaban (366789-02-8,865479-71-6)

Guidance literature:

4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one hydrochloride; With sodium carbonate; In water; acetone; at 8 - 12 ℃;

5-chlorothiophene-2-carbonyl chloride; In water; acetone; at 50 - 53 ℃; for 0.5h; Temperature;

upstream raw materials:

4-[4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]morpholine-3-one

5-chlorothiophene-2-carbonyl chloride

2-((2S)-2-hydroxy-3-{[4-(3-oxomorpholin-4-yl)phenyl]amino}propyl)-1H-isoindole-1,3(2H)-dione

2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-1H-isoindole-1,3(2H)-dione

Downstream raw materials:

5-Chloro-N-(chloroacetyl)-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide

C₃₃H₃₅ClN₄O₈S

C₄₁H₄₃ClN₄O₉S

C₃₂H₃₃ClN₄O₈S

Refernces

• 1、 -. "Preparation method of rivaroxaban". Paragraph 0008; 0017; 0019-0020; 0022-0023; 0025-0026; 0028. . Retrieved 2021/03/18.
• 2、 -. "Preparation method of rivaroxaban". . . Retrieved 2021/01/25.