Orteronel, (R)-

Base Information

• Chemical Name: Orteronel, (R)-
• CAS No.: 752243-39-3
• Molecular Formula: C18H17N3O2
• Molecular Weight: 307.35
• UNII: 267WB8R4TI
• DSSTox Substance ID: DTXSID90226191
• Nikkaji Number: J2.908.584F
• Wikidata: Q27254066
• Pharos Ligand ID: BX7SH2KMLBVL
• ChEMBL ID: CHEMBL1921985
• Mol file: 752243-39-3.mol

Synonyms:6-((7S)-7-hydroxy-6,7-dihydro-5H-pyrrolo(1,2-c)imidazol-7-yl)-N-methyl-2-naphthamide;orteronel;TAK-700

Chemical Property of Orteronel, (R)-

Chemical Property:

• PSA: 67.15000
• Density: 1.35
• LogP: 2.42640
• XLogP3: 1.3
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 307.132076794
• Heavy Atom Count: 23
• Complexity: 471

Purity/Quality:

98%Min ^*data from raw suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CNC(=O)C1=CC2=C(C=C1)C=C(C=C2)C3(CCN4C3=CN=C4)O
• Isomeric SMILES: CNC(=O)C1=CC2=C(C=C1)C=C(C=C2)[C@@]3(CCN4C3=CN=C4)O
• Recent ClinicalTrials: S1216, Phase III ADT+TAK-700 vs. ADT+Bicalutamide for Metastatic Prostate Cancer
• Recent EU Clinical Trials: Open label phase II clinical trial of Orteronel (TAK-700) in metastatic or advanced non-resectable granulosa cell ovarian tumors. The Greko II study.

Technology Process of Orteronel, (R)-

There total 14 articles about Orteronel, (R)- 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: 49.0%

orteronel (426219-18-3,426219-23-0,426219-32-1) → Orteronel (566939-85-3) + 6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methylnaphthalene-2-carboxamide (752243-39-3)

Guidance literature:

With Chiralpak AD column; In ethanol; hexane; optical yield given as %ee; Resolution of racemate; HPLC conditions;

DOI:10.1016/j.bmc.2011.08.068

Reference yield:

6-bromo-2-naphthoic acid (5773-80-8) → Orteronel (566939-85-3) + 6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methylnaphthalene-2-carboxamide (752243-39-3)

Guidance literature:

Multi-step reaction with 3 steps

1.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine / tetrahydrofuran; N,N-dimethyl-formamide / 18 h / 0 - 20 °C / Inert atmosphere

2.1: 2-(trifluoromethyl)phenyllithium / tetrahydrofuran; hexane / 0.83 h / -65 - -55 °C / Inert atmosphere

2.2: 1.5 h / -65 °C / Inert atmosphere

2.3: Inert atmosphere

3.1: Chiralpak AD column / ethanol; hexane / Resolution of racemate; HPLC conditions

With 2-(trifluoromethyl)phenyllithium; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; ethanol; hexane; N,N-dimethyl-formamide;

DOI:10.1016/j.bmc.2011.08.068

Reference yield:

6-bromo-N,N-diisopropyl-2-naphthamide (426219-46-7) → Orteronel (566939-85-3) + 6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methylnaphthalene-2-carboxamide (752243-39-3)

Guidance literature:

Multi-step reaction with 8 steps

1.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.83 h / -70 - -60 °C / Inert atmosphere

1.2: 0.67 h / -70 °C / Inert atmosphere

1.3: Inert atmosphere

2.1: manganese(IV) oxide / dichloromethane / 1.5 h / 20 °C

3.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.5 h / -70 °C / Inert atmosphere

3.2: -70 - -30 °C / Inert atmosphere

3.3: -50 °C / Inert atmosphere

4.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 3 h / -15 - 0 °C

5.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0.5 h / 0 - 10 °C

6.1: acetonitrile / 0.33 h / 70 °C

6.2: 6 h / 70 °C

7.1: n-butyllithium / tetrahydrofuran; hexane / 0.83 h / -78 °C / Inert atmosphere

7.2: 16 h / 0 - 20 °C / Inert atmosphere

7.3: Inert atmosphere

8.1: Chiralpak AD column / ethanol; hexane / Resolution of racemate; HPLC conditions

With manganese(IV) oxide; n-butyllithium; N-ethyl-N,N-diisopropylamine; sodium bis(2-methoxyethoxy)aluminium dihydride; lithium diisopropyl amide; In tetrahydrofuran; ethanol; hexane; dichloromethane; toluene; acetonitrile;

DOI:10.1016/j.bmc.2011.08.068

upstream raw materials:

6-bromo-N,N-diisopropyl-2-naphthamide

6-bromo-N-methyl-2-naphthamide

orteronel

N,N-diisopropyl-6-[1-hydroxy-1-(1-trityl-1H-imidazol-4-yl)methyl]-2-naphthamide

Refernces

• 1、 Gonzalez, Eric,Guengerich, F. Peter. "Kinetic processivity of the two-step oxidations of progesterone and pregnenolone to androgens by human cytochrome P450 17A1". . p. 13168 - 13185. Retrieved 2017/08/21.