188416-20-8

Basic information

• Product Name: 3-(6-Chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride
• Synonyms: 3-(6-Chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride;(2R,3S/2S,3R)-3-(4-Chloro-5-fluoro-6-pyriMidinyl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-;(2R,3S/2S,3R)-3-(4-Chloro-5-fluoro-6-pyriMidinyl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol hydrochloride (for Voriconazole);(αR,βS)-rel-6-chloro-α-(2,4-difluorophenyl)-5-fluoro-β-Methyl-α-(1H-1,2,4-triazol-1-ylMethyl)-4-pyriMidineethanol Monohydrochloride;3-(6-CHLORO-5-FLUOROPYRIMIDIN-4-YL)-2,(2,4-DIFLUORO PHENYL)-1(1H-1,2,4-TRIAZOL-1-YL)BUTANE-2-OL HYDRO CHLORIDE;3-(6-Chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hy;( 2R,3S/2S,3R )-3-(4-chloro-5-fluoro-6-pyriMidinyl)-2-(2,40difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol HCl;Voriconazole PI-5
• CAS NO: 188416-20-8
• Molecular Formula: C₁₆H₁₃ClF₃N₅O*ClH
• Molecular Weight: 420.221
• Mol File: 188416-20-8.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 550.9°C at 760 mmHg
• Flash Point: 287°C
• Appearance: /
• Vapor Pressure: 5.69E-13mmHg at 25°C
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• CAS DataBase Reference: 3-(6-Chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(6-Chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride(188416-20-8)
• EPA Substance Registry System: 3-(6-Chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride(188416-20-8)

Safety Data

• Hazardous Substances Data: 188416-20-8(Hazardous Substances Data)

Usage

Uses

3-(6-Chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1 can be used as organic synthesis intermediates and pharmaceutical intermediates, mainly used in laboratory research and development processes and chemical production processes.

Synthesis

Under nitrogen atmosphere, 9.35 g of zinc powder and 0.47 g of lead are introducedto 53 mL of dry tetrahydrofuran (THF) and the mixture is agitated for 3 hours under reflux. The reaction mixture is cooled to 25°C and agitated continuously for 16 hours. In a separate container, 7.42 g of iodine is dissolved into 21 mL of dry tetrahydrofuran (THF) and the resultant solution is added dropwise to the reaction mixture over 80 minutes. Next, the reaction mixture is warmed to 45°C and then cooled to 0°C.[119] At room temperature, 6.53 g of 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone and 7.01 g of 6-(1-bromo ethyl)-4-chloro-5-fluoropyrimidine are dissolved into 53 mL of tetrahydrofuran (THF) and the resultant solution is added dropwise gradually to the reaction mixture, while maintaining the reaction temperature at 5°C or lower. The reaction mixture is warmed to 25°C and 8.84 g of glacial acetic acid dissolved in 84 mL of purified water is added dropwise to the reaction mixture. The solid metal residueis removed by filtering, the solvent is distilled off under reduced pressure, and the reaction product is extracted twice with 84 mL of ethyl acetate (EA). The extract is washed with 3.22 g of disodium ethylenediamine tetraacetate dihydrate dissolved in 161 mL of purified water, and further washed with 30 mL of saline. The organic layer is concentrated to a final volume of 56 mL, and a solution containing 1.2 g of hydrochloric acid in 6 mL of isopropanol is added dropwise thereto at 25°C. The resultant crystals are filtered, washed with 5 mL of EA, and dried under reduced pressure for 12 hours at 50°C to obtain 5.99 g of the target compound (yield 48.7%, purity 96.2%, HPLC, detected at a wavelength of 256 nm, 18C 4.6 X 250 mm, mobile phase 60% ACN, flow rate 1 mL/min).[120] 1H-NMR (200MHz, DMSO-d6) δ (ppm) : 8.85(1H), 8.731H), 7.93(1H), 7.28~7.16(2H), 6.95~6.89(1H), 5.83(1H), 4.81(1H), 4.54(1H), 3.92(1H), 1.13(3H).

InChI:InChI=1/C16H13ClF3N5O.ClH/c1-9(14-13(20)15(17)23-7-22-14)16(26,5-25-8-21-6-24-25)11-3-2-10(18)4-12(11)19;/h2-4,6-9,26H,5H2,1H3;1H/t9-,16+;/m1./s1

Upstream product

• 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 

Downstream Products

• 137234-62-9 voriconazole 
• 188416-35-5 3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol 
• 188416-34-4 (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (1R)-10-camphorsulfonate 
• 182230-43-9 2-(2,4-Difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol 

Relevant articles and documents

Synthetic method of voriconazole intermediate

The invention provides a synthetic method of a novel voriconazole intermediate condensation compound shown as a formula II or an acid addition salt thereof. The voriconazole intermediate is prepared by compounds shown as a formula III and a formula IV, the feeding way is adjusted, the reaction condition is moderate and controllable, the generation of an impurity A is reduced, the impurity A is controlled within 0.74 percent, the use of toxic metal lead is avoided, and the danger caused by the residue of toxic metal in a drug is eliminated; and the product purity is higher, and the industrial application value is high.

PROCESS FOR PREPARING VORICONAZOLE BY USING NEW INTERMEDIATES

Provided is a process for preparing Voriconazole represented by Chemical Formula 1. More particularly, the process for preparing Voriconazole of Chemical Formula 1 includes: carrying out the Reformatsky-type coupling reaction between a ketone derivative of Chemical Formula 4 and a pyrimidine derivative of Chemical Formula 5 to obtain a compound of Chemical Formula 3; reacting the substituents halo and oxysulfonyl with a hydrogen donor to obtain racemicVoriconazole of Chemical Formula 2; and carrying out optical isolation of the racemicVoriconazole by adding an adequate optically active acid thereto to obtain Voriconazole having high optical purity with high cost-efficiency and high yield.