188416-28-6

Basic information

• Product Name: 6-(1-Bromoethyl)-4-chloro-5-fluoropyrimidine
• Synonyms: 6-(1-Bromoethyl)-4-chloro-5-fluoropyrimidine;6-(1-BroMoethyl)-4-c;PyriMidine, 4-(1-broMoethyl)-6-chloro-5-fluoro-;Voriconazole Impurity 4;-6-chloro-5-fluoropyrimidine;4-chloro-5-fluoro-6-(1-bromoethyl)-pyrimidine
• CAS NO: 188416-28-6
• Molecular Formula: C₆H₅BrClFN₂
• Molecular Weight: 239.47
• Product Categories: pyrimidine;Fluorine series
• Mol File: 188416-28-6.mol
• Article Data: 9

Chemical Properties

• Boiling Point: 257.85 °C at 760 mmHg
• Flash Point: 109.744 °C
• Appearance: /
• Density: 1.725 g/cm³
• Vapor Pressure: 0.023mmHg at 25°C
• Refractive Index: 1.556
• Storage Temp.: 2-8°C
• PKA: -2.62±0.35(Predicted)
• CAS DataBase Reference: 6-(1-Bromoethyl)-4-chloro-5-fluoropyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 6-(1-Bromoethyl)-4-chloro-5-fluoropyrimidine(188416-28-6)
• EPA Substance Registry System: 6-(1-Bromoethyl)-4-chloro-5-fluoropyrimidine(188416-28-6)

Safety Data

• Hazardous Substances Data: 188416-28-6(Hazardous Substances Data)

Usage

General Description

6-(1-Bromoethyl)-4-chloro-5-fluoropyrimidine is a chemical compound with the molecular formula C7H7BrClFN2. It is a pyrimidine derivative that contains a fluoride and a chlorine atom, as well as a bromoethyl group. This chemical compound has potential applications in the pharmaceutical industry, particularly in the development of antiviral or anticancer drugs. Its specific properties and potential uses in the field of medicine make it a subject of interest for researchers and scientists. The synthesis and study of this compound may contribute to the development of novel therapeutic agents.

InChI:InChI=1/C6H5BrClFN2/c1-3(7)5-4(9)6(8)11-2-10-5/h2-3H,1H3

Synthetic route

4-chloro-5-fluoro-6-ethylpyrimidine (137234-74-3) → 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6)

Conditions	Yield
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In dichloromethane at 55℃; for 16h; Temperature;	98%
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In dichloromethane for 12h; Reflux;	95.1%
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In dichloromethane for 12h; Reflux;	95.1%

2,4-dichloro-6-ethyl-5-fluoropyrimidine (137234-85-6) → 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydroxide / water / 0.5 h / 80 - 90 °C 1.2: pH 1 2.1: 5%-palladium/activated carbon; hydrogen / ethanol / 50 °C / 2585.81 Torr 3.1: triethylamine; trichlorophosphate / dichloromethane / 8 h / 40 °C / Reflux 4.1: 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / dichloromethane / 12 h / Inert atmosphere; Reflux View Scheme

2-chloro-6-ethyl-5-fluoro-4-hydroxypyrimidine ammonium salt → 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 5%-palladium/activated carbon; hydrogen / ethanol / 50 °C / 2585.81 Torr 2: triethylamine; trichlorophosphate / dichloromethane / 8 h / 40 °C / Reflux 3: 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / dichloromethane / 12 h / Inert atmosphere; Reflux View Scheme

6-ethyl-5-fluoro-4-hydroxypyrimidine (137234-87-8) → 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine; trichlorophosphate / dichloromethane / 8 h / 40 °C / Reflux 2: 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / dichloromethane / 12 h / Inert atmosphere; Reflux View Scheme

2-fluoro-3-oxopentanoic acid ethyl ester (759-67-1) → 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium methylate / methanol / 20 h / 15 °C 2: trichlorophosphate / 3 h / 60 °C 3: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / 1,2-dichloro-ethane / 15 h / 50 °C View Scheme

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone (86404-63-9) → 3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (188416-35-5)

Conditions	Yield
With lead; samarium diiodide; 1-benzyl-3-(2-pyridylmethyl)-1H-benzimidazolium chloride; iodine; zinc In tetrahydrofuran at -5 - 40℃; for 1.33333h; Inert atmosphere;	87%
With zinc(II) chloride Reformatsky Reaction;
With hydrogenchloride; zinc In tetrahydrofuran; water

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone (86404-63-9) → 3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride salt (188416-20-8)

Conditions	Yield
Stage #1: 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane; 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone With lead; iodine; zinc In tetrahydrofuran at 5 - 25℃; Reformatsky Reaction; Inert atmosphere; Stage #2: With hydrogenchloride In isopropyl alcohol at 25℃;	48.7%
Stage #1: 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane; 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone With lead; bromine; zinc In tetrahydrofuran; dichloromethane at 15 - 50℃; Inert atmosphere; Stage #2: With hydrogenchloride In isopropyl alcohol; acetone at 20 - 25℃; for 2h; Concentration;
With bromine; zinc(II) chloride; zinc In tetrahydrofuran at 15℃; Temperature; Reagent/catalyst; Inert atmosphere;

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone (86404-63-9) → 3-(6-chloro-5-fluoro-4-pyrimidinyl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol hydrochloride

Conditions	Yield
Stage #1: 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane; 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone With lead; chloro-trimethyl-silane; zinc In tetrahydrofuran at 0 - 5℃; for 1.5h; Inert atmosphere; Stage #2: With isopropyl alcohol hydrogen chloride In ethyl acetate at 20℃; for 3h;	57.37%

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + 1-(2,4-difluorophenyl)-2-(1H-tetrazol-1-yl)ethanone (1028563-57-6) → (2S,3R)-3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-tetrazol-1-yl)butan-2-ol + (2R,3S)-3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-tetrazol-1-yl)butan-2-ol

Conditions	Yield
With iodine; zinc; lead In tetrahydrofuran at 0 - 20℃; for 3.16667h;

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone (86404-63-9) → (2R,3S/2S,3R)-3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride

Conditions	Yield
Stage #1: 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane; 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone With lead; iodine; acetic acid; zinc In tetrahydrofuran; water at 0 - 5℃; Inert atmosphere; Stage #2: With hydrogenchloride In water; ethyl acetate; isopropyl alcohol	61.9%
Stage #1: 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane; 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone With lead; iodine; zinc In tetrahydrofuran at 5 - 25℃; Reformatsky Reaction; Inert atmosphere; Stage #2: With hydrogenchloride In isopropyl alcohol at 25℃;	48.7%
Stage #1: 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane; 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone With lead; bromine; zinc In tetrahydrofuran; dichloromethane at 30 - 50℃; Stage #2: With hydrogenchloride In isopropyl alcohol at 20 - 25℃; for 4h; Product distribution / selectivity;

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone (86404-63-9) → (2RS,3SR)-2-(2,4-difluorophenyl)-3-(6-chloro-5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride

Conditions

Yield

Stage #1: 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane With pyridine; zinc/copper couple; Cinchonin In tetrahydrofuran at -5℃; for 2h; Inert atmosphere; Stage #2: 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone In tetrahydrofuran at 0 - 5℃; for 12h; Inert atmosphere; Stage #3: With hydrogenchloride In tetrahydrofuran; water for 0.166667h; Catalytic behavior; Reagent/catalyst; Solvent; Inert atmosphere;

90%

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone (86404-63-9) → (2R,3R/2S,3S)-3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazole-1-yl)butan-2-ol

Conditions	Yield
With iodine In tetrahydrofuran
With iodine In tetrahydrofuran

lead (7439-92-1) + 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone (86404-63-9) → (2R,3R/2S,3S)-3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazole-1-yl)butan-2-ol

Conditions	Yield
With iodine In tetrahydrofuran

lead (7439-92-1) + 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + edetate disodium dihydrate (6381-92-6) + 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone (86404-63-9) + zinc (7440-66-6) → (2R,3R/2S,3S)-3-(4-Chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride

Conditions	Yield
With hydrogenchloride; iodine In tetrahydrofuran; water; acetic acid; ethyl acetate; isopropyl alcohol

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) → voriconazole (137234-62-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: lead; zinc; bromine / dichloromethane; tetrahydrofuran / 30 - 50 °C 1.2: 4 h / 20 - 25 °C 2.1: sodium hydroxide / water; methanol / 20 - 25 °C / pH 8 - 9 2.2: 55 - 60 °C 2.3: 1 h / 40 - 45 °C 3.1: sodium hydroxide / dichloromethane; water / 15 - 25 °C / pH 10 - 11 View Scheme
Multi-step reaction with 4 steps 1.1: zinc; lead / tetrahydrofuran / 1 h / Inert atmosphere; Reflux 2.1: sodium hydroxide / water; dichloromethane / pH 11 2.2: 25 °C / 775.74 Torr 3.1: methanol; acetone / Reflux 4.1: sodium hydroxide / water; dichloromethane / pH 11 View Scheme
Multi-step reaction with 4 steps 1.1: zinc; lead / tetrahydrofuran / 16 °C / Inert atmosphere; Reflux 2.1: sodium hydroxide / water; dichloromethane / pH 11 2.2: 25 °C / 775.74 Torr 3.1: methanol; acetone / Reflux 4.1: sodium hydroxide / water; dichloromethane / pH 11 View Scheme

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone (86404-63-9) → (2S,3R)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol + voriconazole (137234-62-9)

Conditions	Yield
Stage #1: 1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane; 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone With zinc(II) chloride; zinc In tetrahydrofuran at -5 - 5℃; for 1h; Stage #2: With ammonium formate; zinc In methanol at 20℃; for 16h; Stage #3: Product distribution / selectivity; Heating / reflux;

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) → 2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butane-2-ol

Conditions	Yield
Multi-step reaction with 2 steps 1.1: zinc; lead / tetrahydrofuran / 1 h / Inert atmosphere; Reflux 2.1: sodium hydroxide / water; dichloromethane / pH 11 2.2: 25 °C / 775.74 Torr View Scheme
Multi-step reaction with 2 steps 1.1: zinc; lead / tetrahydrofuran / 16 °C / Inert atmosphere; Reflux 2.1: sodium hydroxide / water; dichloromethane / pH 11 2.2: 25 °C / 775.74 Torr View Scheme
Multi-step reaction with 2 steps 1: zinc; lead; iodine; acetic acid / tetrahydrofuran; water / 0 - 5 °C / Inert atmosphere 2: ammonium formate; palladium 10% on activated carbon; water / methanol / 4 h / 60 °C View Scheme

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + N-(3-chlorophenyl)-2-(4-piperidylamino)nicotinamide (1420998-90-8) → 2-{1-[1-(6-chloro-5-fluoropyrimidin-4-yl)ethyl]piperidin-4-ylamino}-N-(3-chlorophenyl)pyridine-3-carboxamide (1420999-05-8)

Conditions	Yield
With potassium carbonate In acetonitrile for 24h; Reflux;	48%

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone (86404-63-9) → 3-(6-chloro-5-fluoro-4-pyrimidinyl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol hydrochloride + 3-(6-chloro-5-fluoro-4-pyrimidinyl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol hydrochloride + C22H18ClF4N7O

Conditions	Yield
With lead; zinc In tetrahydrofuran at 16℃; Reagent/catalyst; Temperature; Inert atmosphere; Reflux;	A 47.5 %Chromat. B 24 %Chromat. C 9.2 %Chromat.

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) → (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (1R)-10-camphorsulfonate (188416-34-4, 137234-71-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: zinc; lead / tetrahydrofuran / 1 h / Inert atmosphere; Reflux 2.1: sodium hydroxide / water; dichloromethane / pH 11 2.2: 25 °C / 775.74 Torr 3.1: methanol; acetone / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: zinc; lead / tetrahydrofuran / 16 °C / Inert atmosphere; Reflux 2.1: sodium hydroxide / water; dichloromethane / pH 11 2.2: 25 °C / 775.74 Torr 3.1: methanol; acetone / Reflux View Scheme

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone (86404-63-9) → 3-(6-chloro-5-fluoro-4-pyrimidinyl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol hydrochloride + 3-(6-chloro-5-fluoro-4-pyrimidinyl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol hydrochloride

Conditions	Yield
With lead; zinc In tetrahydrofuran for 1h; Reagent/catalyst; Temperature; Inert atmosphere; Reflux; Overall yield = 65 %; Overall yield = 7.89 g;	A n/a B n/a

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) → voriconazole L-camphorsulfate

Conditions	Yield
Multi-step reaction with 2 steps 1.1: lead; zinc; bromine / dichloromethane; tetrahydrofuran / 30 - 50 °C 1.2: 4 h / 20 - 25 °C 2.1: sodium hydroxide / water; methanol / 20 - 25 °C / pH 8 - 9 2.2: 55 - 60 °C 2.3: 1 h / 40 - 45 °C View Scheme

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) → (2RS,3SR)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol

Conditions	Yield
Multi-step reaction with 2 steps 1.1: zinc/copper couple; pyridine; Cinchonin / tetrahydrofuran / 2 h / -5 °C / Inert atmosphere 1.2: 12 h / 0 - 5 °C / Inert atmosphere 1.3: 0.17 h / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen; sodium carbonate / ethanol / 20 - 25 °C / 760.05 Torr View Scheme

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) → voriconazole L-camphor sulfonate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: zinc/copper couple; pyridine; Cinchonin / tetrahydrofuran / 2 h / -5 °C / Inert atmosphere 1.2: 12 h / 0 - 5 °C / Inert atmosphere 1.3: 0.17 h / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen; sodium carbonate / ethanol / 20 - 25 °C / 760.05 Torr 3.1: methanol; acetone / Reflux View Scheme

1-(4-chloro-5-fluoropyrimidin-6-yl)bromoethane (188416-28-6) + 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone (86404-63-9) → voriconazole (137234-62-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: iodine; zinc; lead; samarium diiodide; 1-benzyl-3-(2-pyridylmethyl)-1H-benzimidazolium chloride / tetrahydrofuran / 1.33 h / -5 - 40 °C / Inert atmosphere 2.1: sodium acetate; 5%-palladium/activated carbon; hydrogen / methanol / 25 °C / 760.05 Torr 2.2: 2 h / Reflux View Scheme

Upstream product

• 759-67-1 2-fluoro-3-oxopentanoic acid ethyl ester 
• 137234-87-8 6-ethyl-5-fluoro-4-hydroxypyrimidine 
• 137234-85-6 2,4-dichloro-6-ethyl-5-fluoropyrimidine 
• 137234-74-3 4-chloro-6-ethyl-5-fluoropyrimidine 

Downstream Products

• 188416-20-8 3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride salt 
• 137234-63-0 (2RS,3SR)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-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 
• 137234-63-0 2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butane-2-ol 
• 1420999-05-8 2-{1-[1-(6-chloro-5-fluoropyrimidin-4-yl)ethyl]piperidin-4-ylamino}-N-(3-chlorophenyl)pyridine-3-carboxamide 
• 137234-62-9 voriconazole 
• 137234-63-0 (2S,3R)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol 
• 188416-35-5 3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol 

Relevant articles and documents

Preparation method of voriconazole intermediate

The invention is suitable for the technical field of chemical synthesis and medicine, and provides a preparation method of voriconazole intermediate, which comprises steps of: carrying out a bromination reaction on 4-chloro-6-ethyl-fluoropyrimidine, N-bromosuccinimide, azodiisobutyronitrile and a first solvent to obtain a first intermediate; carrying out condensation reaction on the first intermediate, 2',4'-difluoro-2-[1-(1H-1,2,4-triazolyl)]acetophenone, zinc powder subjected to acid treatment and a second solvent to obtain a second intermediate; mixing the second intermediate, a third solvent and potassium formate to obtain a mixed solution; and adding palladium carbon into the mixed solution, and carrying out reflux reaction in a protective atmosphere to obtain the voriconazole intermediate. According to the preparation method disclosed by the invention, the voriconazole intermediate with high yield and high purity can be prepared.

NOVEL COMPOUND HAVING ANGIOGENESIS INHIBITORY ACTIVITY, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING SAME

Disclosed are an anti-angiogenic compound, represented by Chemical Formula I, or a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutically acceptable composition including the same. Because the compound of Chemical Formular I potently suppresses the angiogenesis, the compound of Chemical Formula I is applicable to the prevention and treatment of diseases caused by aberrant activity of vascular endothelial growth factor, and available as an anti-angiogenic agent.

PROCESS FOR THE PREPARATION OF VORICONAZOLE AND INTERMEDIATES THEREOF

The present invention relates to an improved stereoselective process for the preparation of (2R,3S/2S,3R)-3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol intermediate compound. This intermediate compound is further used to prepare voriconazole—a triazole antifungal agent.