Ravuconazole

Base Information

• Chemical Name: Ravuconazole
• CAS No.: 182760-06-1
• Molecular Formula: C22H17F2N5OS
• Molecular Weight: 437.473
• UNII: 95YH599JWV
• DSSTox Substance ID: DTXSID40171329
• Nikkaji Number: J772.209E
• Wikipedia: Ravuconazole
• Wikidata: Q7296826
• NCI Thesaurus Code: C38688
• Metabolomics Workbench ID: 149778
• ChEMBL ID: CHEMBL294029
• Mol file: 182760-06-1.mol

Synonyms:3-(4-(4-cyanophenyl)thiazol-2-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol;BMS-207147;ER 30346;ER-30346;ravuconazole

Chemical Property of Ravuconazole

Chemical Property:

• Vapor Pressure: 3.89E-19mmHg at 25°C
• Melting Point: 64-66°C
• Boiling Point: 674.9°C at 760 mmHg
• PKA: 11.62±0.29(Predicted)
• Flash Point: 362°C
• PSA: 115.86000
• Density: 1.38g/cm³
• LogP: 4.24298
• Storage Temp.: -20?C Freezer
• XLogP3: 3.5
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 6
• Exact Mass: 437.11218768
• Heavy Atom Count: 31
• Complexity: 657

Purity/Quality:

99.0% ^*data from raw suppliers

Ravuconazole 99.63% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C1=NC(=CS1)C2=CC=C(C=C2)C#N)C(CN3C=NC=N3)(C4=C(C=C(C=C4)F)F)O
• Isomeric SMILES: C[C@@H](C1=NC(=CS1)C2=CC=C(C=C2)C#N)[C@](CN3C=NC=N3)(C4=C(C=C(C=C4)F)F)O
• Recent ClinicalTrials: Ravuconazole in Preventing Fungal Infections in Patients Undergoing Allogeneic Stem Cell Transplantation
• Description: Ravuconazole is an orally available triazole fungicide that potently inhibits the growth of a wide range of fungi (MICs range from 25 to 780 ng/ml). Like other azoles, ravuconazole inhibits cytochrome P450 (CYP) isoforms that are involved in ergosterol biosynthesis, interfering with the generation of the fungal and protozoan cell membranes. Ravuconazole specifically inhibits sterol 14α-demethylase (CYP51). As this enzyme is also important in the development of trypanosomes, ravuconazole is effective against T. cruzi infections in animal models of Chagas disease.

Technology Process of Ravuconazole

There total 18 articles about Ravuconazole 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: 85.8%

(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanethioamide hydrosulfate (1175536-51-2) + 4-Cyanophenacyl bromide (20099-89-2) → ravuconazole (182760-06-1)

Guidance literature:

(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanethioamide hydrosulfate; 4-Cyanophenacyl bromide; In ethanol; water; at 60 - 70 ℃; for 2h; Large scale reaction;

With triethylamine; In ethanol; water; at 55 - 70 ℃; pH=3.5 - 4; Large scale reaction;

DOI:10.1021/op900065c

Reference yield: 79.5%

4-Cyanophenacyl bromide (20099-89-2) + (2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanethioamide (170863-34-0) → ravuconazole (182760-06-1)

Guidance literature:

In ethanol; for 3h; Reflux;

DOI:10.1080/00397910802563420

Reference yield:

(2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-butan-2-ol (1R)-10-camphorsulfonate → ravuconazole (182760-06-1)

Guidance literature:

With sodium hydroxide; In dichloromethane; water; Product distribution / selectivity;

upstream raw materials:

4-Cyanophenacyl bromide

(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanethioamide

4-cyanophenyl methyl ketone

(2S,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanenitrile

Downstream raw materials:

(2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-[[[m-chloromethyl]benzoyloxy]methoxy]butane

carbonic acid chloromethyl ester 2-[4-(4-cyanophenyl)-thiazol-2-yl]-1-(2,4-difluorophenyl)-1-[1,2,4]triazol-1-yl-methylpropyl ester

4-(2-((R)-1-((R)-6-(2,4-difluorophenyl)-8-oxo-6,8-dihydro-5H-[1,2,4]triazolo[5,1-c][1,4]oxazin-6-yl)ethyl)thiazol-4-yl)benzonitrile

2-[3-[4-(4cyanophenyl)-thiazol-2-yl]-2-(2,4-difluorophenyl)-2-hydroxy-butyl]-2H-[1,2,4]triazole-3-carboxylic acid chloromethyl ester

Refernces

• 1、 Tamura, Keiji,Kumagai, Naoya,Shibasaki, Masakatsu. "An enantioselective synthesis of the key intermediate for triazole antifungal agents; Application to the catalytic asymmetric synthesis of efinaconazole (jublia)". supporting information. p. 3272 - 3278. Retrieved 2014/05/06.
• 2、 Xu, Lin,Muller, Marc R.,Yu, Xiong,Zhu, Bao-Quan. "Improved chiral synthesis of ravuconazole". experimental part. p. 1611 - 1625. Retrieved 2009/10/17.