188416-29-7

Basic information

• Product Name: (2R,3S/2S,3R)-2-(2,4-Difluorophenyl)-3-(5-fluoro-4-pyriMidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (RaceMic Voriconazole)
• Synonyms: (2R,3S/2S,3R)-2-(2,4-Difluorophenyl)-3-(5-fluoro-4-pyriMidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (RaceMic Voriconazole);(2S,3R)-2-(2,4-Difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol;(2S,3R)-rel-2-(2,4-Difluorophenyl)-3-(5-fluoropyriMidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol;Voriconazole PI-6;(2R,3R)-Voriconazole
• CAS NO: 188416-29-7
• Molecular Formula: C16H14F3N5O
• Molecular Weight: 349.3104696
• EINECS: 1312995-182-4
• Mol File: 188416-29-7.mol
• Article Data: 40

Chemical Properties

• Boiling Point: 508.6±60.0 °C(Predicted)
• Appearance: white powder
• Density: 1.42±0.1 g/cm3(Predicted)
• PKA: 11.54±0.29(Predicted)
• CAS DataBase Reference: (2R,3S/2S,3R)-2-(2,4-Difluorophenyl)-3-(5-fluoro-4-pyriMidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (RaceMic Voriconazole)(CAS DataBase Reference)
• NIST Chemistry Reference: (2R,3S/2S,3R)-2-(2,4-Difluorophenyl)-3-(5-fluoro-4-pyriMidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (RaceMic Voriconazole)(188416-29-7)
• EPA Substance Registry System: (2R,3S/2S,3R)-2-(2,4-Difluorophenyl)-3-(5-fluoro-4-pyriMidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (RaceMic Voriconazole)(188416-29-7)

Safety Data

• Hazardous Substances Data: 188416-29-7(Hazardous Substances Data)

Usage

Description

Voriconazole-d3 is a labeled form of Voriconazole which is an Ergosterol biosynthesis inhibitor. This monotriazole antifungal agent inhibits the growth of Candida, Cryptococcus, and Aspergillus species. Studies suggest that Voriconazole-d3 can be synthesized by modifying the structure of fluconazole. This antifungal agent functions by inhibiting cytochrome P450 dependent 14-α-sterol demethylase, which is responsible in the biosynthesis of Ergosterol. Furthermore, Voriconazole-d3 inhibits fungal growth, cell wall thinning, and cell membrane degradation.

Uses

Voriconazole is a triazole antifungal agent used primarily in the treatment or prevention of aspergillosis and candidal infections. Voriconazole therapy is associated with transient, asymptomatic serum aminotransferase elevations and is a known cause of clinically apparent acute drug induced liver injury.

Application

Voriconazole-d3 is derived from 2,4-Difluoro-α-(1H-1,2,4-triazolyl)acetophenone, which is an antifungal activity, particularly toward Candida albicans and Candida parapsilosis.

References

1. Voriconazole (UK-109,496) inhibits the growth and alters the morphology of fluconazole-susceptible and -resistant Candida speciesBelanger, P., et al. 1997. Antimicrob. Agents Chemother. 41: 1840-1842. PMID: 92577762. In vitro activities of voriconazole (UK-109,496) and four other antifungal agents against 394 clinical isolates of Candida sppMarco, F., et al. 1998. Antimicrob. Agents Chemother. 42: 161-163. PMID: 94492783. In vitro activity of the new triazole voriconazole (UK-109,496) against opportunistic filamentous and dimorphic fungi and common and emerging yeast pathogensEspinel-Ingroff, A. 1998. J. Clin. Microbiol. 36: 198-202. PMID: 9431946

Upstream product

• 759-67-1 2-fluoro-3-oxopentanoic acid ethyl ester 
• 137234-87-8 6-Ethyl-5-fluoropyrimidin-4(3H)-one 
• 137234-74-3 4-chloro-6-ethyl-5-fluoropyrimidine 
• 188416-28-6 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane 
• 86404-63-9 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone 
• 1474024-65-1 (R)-((R)-2-(2,4-difluorophenyl)oxiran-2-yl)(5-fluoropyrimidin-4-yl)methanol 
• 1474024-66-2 (R)-(2-(2,4-difluorophenyl)oxiran-2-yl)(5-fluoropyrimidin-4-yl)-methanone 
• 1474024-67-3 (R)-4-(1-(2-(2,4-difluorophenyl)oxirane-2-yl)vinyl)-5-fluoropyrimidine 
• 288-88-0 1,2,4-Triazole 
• 1474024-68-4 4-((S)-1-((R)-2-(2,4-difluorophenyl)oxirane-2-yl)ethyl)-5-fluoropyrimidine 
• 1403893-61-7 4-chloro-5-fluoro-6-vinylpyrimidine 
• 898044-55-8 4-chloro-5-fluoro-6-methylpyrimidine 
• 861718-85-6 3-chloro-2-(2,4-difluorophenyl)-2-(trimethylsilanyloxy)propionaldehyde 
• 182230-43-9 2-(2,4-Difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol 

Downstream Products

• 1631143-19-5 C₁₆H₁₄F₃N₅O*C₇H₆O₃ 
• 1631143-18-4 C₁₆H₁₄F₃N₅O*C₇H₇NO₂ 
• 1631143-20-8 C₁₆H₁₄F₃N₅O*C₇H₅NO₄ 
• 1620283-07-9 C₁₆H₁₃F₃N₆O₃ 
• 1620283-08-0 C₁₆H₁₅F₃N₆O 
• 1620283-05-7 C₂₀H₁₉F₃N₆O₄ 
• 1620283-09-1 C₂₄H₂₂F₃N₇O₆ 
• 1620283-06-8 C₁₉H₁₉F₂N₇O₅ 

Relevant articles and documents

Voriconazole synthesis process

The invention discloses a synthesis process of voriconazole bulk drug, which comprises the following steps: preparing halogenated ethyl fluorouracil and carrying out Grignard reaction. 2 - (2, 4 - Difluorophenyl) -3 - (1, 2, 4 - triazol -1 -yl) -1, 2 - propylene glycol was oxidized to give a propylene oxide compound. The Grignard reagent and the propylene oxide compound are mixed and reacted to obtain voriconazole. To the synthesis process, the reaction steps can be simplified, the dehydrochlorination and hydrogenolysis of palladium carbon are not needed, the reaction period is shortened, and furthermore, the energy consumption is reduced, the cost is reduced, and voriconazole and the racemate thereof are obtained with higher yield.

Synthesis method of voriconazole and intermediate of voriconazole

The invention relates to a synthesis method of voriconazole and an intermediate of voriconazole. The synthesis method comprises the following step: in a protective gas atmosphere, reacting a compoundshown in formula I and a compound shown in formula II in an organic solvent under the action of a metal catalyst, N-heterocyclic carbene, samarium diiodide and elemental iodine to obtain the voriconazole intermediate shown in formula III. According to the synthesis method of the voriconazole intermediate, under the action of the metal catalyst and SmI2, N-heterocyclic carbene is simultaneously added as a ligand, and elemental iodine is used as an initiator to initiate a reformask coupling reaction between the compound shown in formula I and the compound shown in formula II, so that the defectsof low yield, more byproducts and the like of the traditional reaction are overcome, and the yield and the purity are further improved.

Voriconazole synthesis method

The invention relates to a voriconazole synthesis method, which comprises: 1, carrying out catalytic hydrogenation on an SM, anhydrous methanol and anhydrous sodium acetate reaction system by using palladium carbon; after treatment, crystallization is performed to obtain a voriconazole racemate; 2, the voriconazole racemate, an acetone solvent and an L(-)-camphor-10-sulfonic acid system are subjected to a reflux reaction, crystallization and filtration are performed after the reaction is completed, voriconazole camphorsulfonate is obtained, and the molar ratio of L-camphorsulfonic acid to thevoriconazole racemate is 0.5:1; and 3, adjusting the pH value of the voriconazole camphor sulfonate, dichloromethane and water system to 10-11 by using a sodium hydroxide aqueous solution, layering, and temporarily storing an organic phase; extracting the water phase with dichloromethane; and merging the organic phases, carrying out reduced pressure distillation to remove the solvent, and carryingout post-treatment to obtain voriconazole.