Bedaquiline

Base Information

• Chemical Name: Bedaquiline
• CAS No.: 654653-93-7
• Molecular Formula: C32H31BrN2O2
• Molecular Weight: 555.5047
• 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: 654653-93-7.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:

• Vapor Pressure: 1.01E-20mmHg at 25°C
• Melting Point: >180°C (dec.)
• Boiling Point: 702.7°Cat760mmHg
• PKA: 13.05±0.29(Predicted)
• Flash Point: 378.8°C
• PSA: 45.59000
• Density: 1.322g/cm³
• LogP: 7.13050
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility.: Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)
• 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:

NLT 98% ^*data from raw suppliers

(αR,βS)-rel-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)
• Uses: (αR,βS)-rel-Bedaquiline is a promising diarylquinoline candidate in clinical development for the treatment of tuberculosis. (αR,βS)-rel-Bedaquiline inhibits mycobacterial ATP synthase and displays high activity against both drug-susceptible and multidrug-resistant strains of Mycobacterium tuberculosis.

Technology Process of Bedaquiline

There total 91 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