Bedaquiline

Base Information

• Chemical Name: Bedaquiline
• CAS No.: 843663-66-1
• Molecular Formula: C32H31BrN2O2
• Molecular Weight: 555.514
• Hs Code.: 2933499090
• European Community (EC) Number: 831-215-5
• UNII: 78846I289Y
• DSSTox Substance ID: DTXSID101027810,DTXSID80903989
• Nikkaji Number: J2.291.406E
• Wikipedia: Bedaquiline
• Wikidata: Q1257318
• NCI Thesaurus Code: C87658
• RXCUI: 1364504
• Pharos Ligand ID: 1M491KZVZLHN
• Metabolomics Workbench ID: 65915
• ChEMBL ID: CHEMBL376488
• Mol file: 843663-66-1.mol

Synonyms:(1R,2S)-1-(6-bromo-2-methoxy-quinolin-3-yl)-4-dimethylamino-2-(3-fluorophenyl)-1-phenyl-butan-2-ol;AIDS-222089;AIDS222088;Bedaquiline;bedaquiline fumarate;R207910;TMC207

Chemical Property of Bedaquiline

Chemical Property:

• Melting Point: 104 °C
• Boiling Point: 702.7 °C at 760 mmHg
• PKA: 13.05±0.29(Predicted)
• Flash Point: 378.8 °C
• PSA: 45.59000
• Density: 1.322 g/cm³
• LogP: 7.13050
• Storage Temp.: Room temperature
• Solubility.: Soluble in DMSO (10 mg/ml)
• XLogP3: 7.2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 8
• Exact Mass: 554.15689
• Heavy Atom Count: 37
• Complexity: 715

Purity/Quality:

98%min ^*data from raw suppliers

Bedaquiline ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antituberculosis Agents
• Canonical SMILES: CN(C)CCC(C1=CC=CC2=CC=CC=C21)(C(C3=CC=CC=C3)C4=C(N=C5C=CC(=CC5=C4)Br)OC)O
• Isomeric SMILES: CN(C)CC[C@@](C1=CC=CC2=CC=CC=C21)([C@H](C3=CC=CC=C3)C4=C(N=C5C=CC(=CC5=C4)Br)OC)O
• Recent ClinicalTrials: Pharmacokinetic Study to Evaluate Anti-mycobacterial Activity of TMC207 in Combination With Background Regimen (BR) of Multidrug Resistant Tuberculosis (MDR-TB) Medications for Treatment of Children/Adolescents Pulmonary MDR-TB
• Recent EU Clinical Trials: A Phase I, open-label, randomized, 3-way crossover study in 3 Panels of healthy, adult subjects to assess the relative bioavailability of TMC207 following single-dose administration of two pediatric formulations using a 100 mg tablet formulation as the reference, with and without food.
• Recent NIPH Clinical Trials: A Study of Bedaquiline Administered as Part of a Treatment Regimen With Clarithromycin and Ethambutol in Adult Patients With Treatmentrefractory Mycobacterium Avium Complex-lung Disease (MAC-LD)
• Description: In December 2012, the US FDA approved bedaquiline as part of combination therapy for the treatment of multi-drug resistant tuberculosis (MDRTB). Bedaquiline is the first drug approved for MDR-TB and is the first approval from a new class of antituberculosis agents in the past 40 years. Due to the high unmetmedical need for treating MDR-TB, the FDA granted bedaquiline accelerated approval based on Phase II results, providing patients access to the drug while additional clinical studies are carried out. Bedaquiline (also known as TMC207 and R207910) is a diarylquinoline that was discovered from a high-throughput, whole-cell screening strategy with Mycobacterium smegmatis used as a surrogate for M. tuberculosis. Bedaquiline is a single enantiomer of an initial screening hit. Bedaquiline has potent and selective activity against mycobacteria, and is active against both drug-sensitive and drug-resistant M. tuberculosis. The mechanism of action of bedaquiline is unique amongst anti-TB drugs and involves inhibition of mycobacterial ATP synthase; it is not active against human ATP synthase. Bedaquiline has in vivo activity in numerous preclinical models of TB infection, alone and in combination with other anti-TB agents, and has bactericidal activity in established TB infection models. Bedaquiline is synthesized in five steps from 3-phenylpropionic acid and para-bromoaniline. Following amide formation, treatment with POCl3 and DMF under Vilsmeier–Hack conditions gave a 2-chloroquinoline product. Treatment with sodium methoxide, followed by condensation with 3-(dimethylamino)-1-(naphthalen-1-yl)propan-1-one, and separation of isomers gave bedaquiline. TMC207 is a diarylquinoline that selectively inhibits the proton pump of the mycobacterial ATP synthase. It demonstrates potent activity against both drug-sensitive and drug-resistant M. tuberculosis and other mycobacterial species with MIC50 values of ~0.03 μg/ml.
• Uses: (αS,βR)-Bedaquiline is a diarylquinoline derivative that acts as a mycobacterial inhibitor. Bedaquiline shows promise as potential drug in the treatment of tuberculosis. Labeled Bedaquiline, intended for use as an internal standard for the quantification of Bedaquiline by GC- or LC-mass spectrometry.

Technology Process of Bedaquiline

There total 35 articles about Bedaquiline 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: 62.0%

(3S,4R)-4-(6-bromo-2-methoxyquinolin-3-yl)-3-hydroxy-3-(naphthalen-1-yl)-4-phenylbutyl-4-methylbenzenesulfonate (1229443-16-6) + dimethyl amine (124-40-3) → bedaquiline (843663-66-1,654653-93-7,857086-92-1)

Guidance literature:

In water; N,N-dimethyl-formamide; at 40 ℃; for 10h; Inert atmosphere;

DOI:10.1021/ja103183r

Reference yield: 39.0%

1-(6-bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(naphthalen-1-yl)-1-phenylbutan-2-ol (654655-80-8,654653-93-7,857086-92-1) → bedaquiline (843663-66-1,654653-93-7,857086-92-1)

Guidance literature:

With (R)-1,1'-binaphthyl-2,2'-phosphoric acid; In dimethyl sulfoxide; acetone; at 20 ℃; for 3h; Reflux;

Reference yield: 39.0%

rac-(1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-dimethylamino-2-(1-naphthyl)-1-phenylbutan-2-ol (654653-93-7,857086-92-1) + 6-bromo-α-[2-(dimethylamino)ethyl]-2-methoxy-α-1-naphthalenyl-β-phenyl-3-quinolineethanol*(11bR)-4-hydroxydinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin 4-oxide (916329-20-9) → bedaquiline (843663-66-1,654653-93-7,857086-92-1)

Guidance literature:

rac-(1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-dimethylamino-2-(1-naphthyl)-1-phenylbutan-2-ol; 6-bromo-α-[2-(dimethylamino)ethyl]-2-methoxy-α-1-naphthalenyl-β-phenyl-3-quinolineethanol*(11bR)-4-hydroxydinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin 4-oxide; With (R)-1,1'-binaphthyl-2,2'-phosphoric acid; In dimethyl sulfoxide; acetone; at 20 - 50 ℃; for 3.16667 - 5.75h; Heating / reflux; Resolution of racemate;

In acetone; at 20 - 30 ℃; for 2.75 - 4h; Heating / reflux;

With potassium carbonate; In water; toluene; at 80 - 85 ℃; for 0.0833333 - 0.25h; Purification / work up;

upstream raw materials:

3-(dimethylamino)-1-(1-naphthalenyl)-1-propanone

rac-(1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-dimethylamino-2-(1-naphthyl)-1-phenylbutan-2-ol

6-bromo-α-[2-(dimethylamino)ethyl]-2-methoxy-α-1-naphthalenyl-β-phenyl-3-quinolineethanol*(11bR)-4-hydroxydinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin 4-oxide

(3S,4R)-4-(6-bromo-2-methoxyquinolin-3-yl)-3-hydroxy-3-(naphthalen-1-yl)-4-phenylbutyl-4-methylbenzenesulfonate

Downstream raw materials:

C₃₉H₃₅BrN₂O₃

C₃₉H₃₇BrN₂O₃

[4-(6-bromo-2-methoxyquinolin-3-yl)-3-hydroxy-3-(naphthalen-1-yl)-4-phenylbutyl]dimethylazanium 3-carboxyprop-2-enoate

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