Synthesis of Isomeric and Potent Impurities of the Triazole-Based Antifungal Drug Voriconazole

被引：4

作者：

Sundaram, Dhanraj T. S. S. ^{[1
,2
]}

Mitra, Jayati ^{[1
]}

Islam, Aminul ^{[1
]}

Prabahar, Koilpillai Joseph ^{[1
]}

Rao, Battula Venkateswara ^{[2
]}

Douglas, Sanasi Paul ^{[2
]}

机构：

[1] Aurobindo Pharma Ltd, APL Res Ctr 2, Chem Res & Dev, Survey 71 & 72, Indrakaran V 502329, Andhra Pradesh, India

[2] Andhra Univ, Dept Chem Engn, Coll Engn A, Visakhapatnam 530003, Andhra Pradesh, India

来源：

SCIENTIA PHARMACEUTICA | 2015年 / 83卷 / 03期

关键词：

Voriconazole; Impurity synthesis; Positional isomers; Chloroacetyl chloride;

D O I：

10.3797/scipharm.1501-13

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

We describe the synthesis of two positional isomers and a desfluoro impurity of Voriconazole starting with Friedel-Crafts acylation of mono-and difluorobenzene. These isomers are the crucial components in determining the quality of Voriconazole during its manufacturing from the key raw material, 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one. All the prepared impurities were characterized by IR, H-1-NMR, C-13-NMR, and mass spectral data.

引用

页码：445 / 452

页数：8

共 7 条

[1] Process development of voriconazole: A novel broad-spectrum triazole antifungal agent [J].

Butters, M ;

Ebbs, J ;

Green, SP ;

MacRae, J ;

Morland, MC ;

Murtiashaw, CW ;

Pettman, AJ .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2001, 5 (01) :28-36

[2] Novel antifungal 2-aryl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol derivatives with high activity against Aspergillus fumigatus. [J].

Dickinson, RP ;

Bell, AS ;

Hitchcock, CA ;

Narayanaswami, S ;

Ray, SJ ;

Richardson, K ;

Troke, PF .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (16) :2031-2036

[3]

International Conference on Harmonization (ICH) guidelines, 2002, Q3A R IMP NEW DRUG S

[4]

International Conference on Harmonization (ICH) guidelines, 1996, Q2B VAL AN PROC METH

[5] Highly reactive and regenerable fluorinating agent for oxidative fluorination of aromatics [J].

Janmanchi, Krishna Murthy ;

Dolbier, William R., Jr. .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2008, 12 (02) :349-354

[6]

Richardson K., 1996, Triazole antifungal agents, Patent No. [US5567817A, 5567817]

[7]

Sundaram V, 2011, Process for preparing (2R, 3S/ 2S, 3R)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl) butan-2-ol, Patent No. [US 8039619B2, 8039619]

← 1 →