161798-01-2

Basic information

• Product Name: ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl thiazole-5-carboxylate
• Synonyms: ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl thiazole-5-carboxylate;2-(3-Formyl-4-hydroxy-phenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester;Thiazolecarboxylicacid,2-(3-forMyl-4-hydroxyphenyl)-4-Methyl-,ethylester;5-carboxylato-1-ethyl-2-(3-forMyl-4-hydroxyphenyl)-4-Methyl-1H-1$l^{4},3-thiazol-1-yl;Ethyl 2-(3-forMyl-4-hydroxyphenyl)-4-Methyl-5-Thiazolecarboxylate;5-carboxylato-1-ethyl-2-(3-forMyl-4-h;ETHYL 2-(3-FORMYL-4-HYDROXYPHENYL)-4-METHYL-1,3-THIAZOLE-5-CARBOXYLATE;2-(3-forMyl-4-hydroxyphenyl)-4-Methyl-5-Thiazolecarboxylicacid ethyl ester
• CAS NO: 161798-01-2
• Molecular Formula: C₁₄H₁₃NO₄S
• Molecular Weight: 291.32
• EINECS: 1592732-453-0
• Product Categories: Febuxostat intermediate
• Mol File: 161798-01-2.mol
• Article Data: 16

Chemical Properties

• Melting Point: 116 °C
• Boiling Point: 446.7 °C at 760 mmHg
• Flash Point: 223.9 °C
• Appearance: /
• Density: 1.335
• Refractive Index: 1.625
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 6.81±0.20(Predicted)
• CAS DataBase Reference: ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl thiazole-5-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl thiazole-5-carboxylate(161798-01-2)
• EPA Substance Registry System: ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl thiazole-5-carboxylate(161798-01-2)

Safety Data

• Hazardous Substances Data: 161798-01-2(Hazardous Substances Data)

Usage

Description

Ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl thiazole-5-carboxylate is a chemical compound derived from the reaction between 4-Hydroxybenzene-1-benzothiomide and ethyl-2-chloro acetoacetate. It is characterized by its yellow or yellow powder appearance and is known for its antibacterial and antifungal properties.

Uses

Used in Pharmaceutical Industry:
Ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl thiazole-5-carboxylate is used as an active pharmaceutical ingredient for its antibacterial and antifungal properties, particularly effective against C. albicans. Its chemical structure allows it to target and inhibit the growth of harmful microorganisms, making it a valuable compound in the development of new drugs to combat bacterial and fungal infections.
Used in Agricultural Industry:
In the agricultural sector, ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl thiazole-5-carboxylate can be utilized as a biopesticide. Its antifungal and antibacterial activities can help protect crops from diseases caused by various pathogens, thereby increasing crop yield and quality.
Used in Cosmetics Industry:
The compound can also be employed in the cosmetics industry, where it can serve as a preservative to prevent the growth of bacteria and fungi in cosmetic products. This application helps maintain the shelf life and safety of cosmetics, ensuring that they remain free from harmful microorganisms.
Used in Research and Development:
Ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl thiazole-5-carboxylate holds potential for further research and development in various scientific fields. Its unique chemical properties and biological activities make it an interesting candidate for exploring new applications and understanding its mechanisms of action against different types of microorganisms.

InChI:InChI=1/C14H13NO4S/c1-3-19-14(18)12-8(2)15-13(20-12)9-4-5-11(17)10(6-9)7-16/h4-7,17H,3H2,1-2H3

Synthetic route

(2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester) (161797-99-5) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2)

Conditions	Yield
Stage #1: (2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester) With n-butyllithium In tetrahydrofuran; hexane at -10℃; for 0.2h; Inert atmosphere; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran; hexane at -10℃; for 0.5h; Inert atmosphere; Stage #3: With acetic acid In tetrahydrofuran; hexane at 10℃; for 0.166667h; Time; Inert atmosphere;	96.6%

(2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester) (161797-99-5) + hexamethylenetetramine (100-97-0) → ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2)

Conditions	Yield
With methanesulfonic acid; boric acid In cyclohexane at 75 - 100℃; for 7h; Temperature; Reagent/catalyst; Solvent; Duff Aldehyde Synthesis;	91.2%
Stage #1: (2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester) With methanesulfonic acid; boric acid In cyclohexane at 80℃; Stage #2: hexamethylenetetramine In cyclohexane at 75℃; for 7h; Temperature;	91.2%
With water; acetic acid; trifluoroacetic acid at 100℃; for 2.5h;	90%

ethyl 2-bromoacetoacetate (84911-18-2, 609-13-2) + hexamethylenetetramine (100-97-0) → ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2)

Conditions	Yield
With trifluoroacetic acid for 20h; Reflux;	80%

hexamethylenetetramine (100-97-0) + 2-(4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylic acid ethyl ester hydrochloride → ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2)

Conditions	Yield
With phosphoric acid at 70 - 95℃;	75.2%

(2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester) (161797-99-5) + acetic acid (64-19-7) → ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2)

Conditions	Yield
Stage #1: (2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester); acetic acid With hexamethylenetetramine at 90℃; for 12h; Stage #2: With hydrogenchloride In water at 75℃; for 0.5h;	29%
With hydrogenchloride; hexamethylenetetramine In water at 90℃; for 12h;

ethyl 2-chloro-3-oxo-butyrate (609-15-4) → ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: spirit / 2.5 h / 60 - 65 °C 2: methanesulfonic acid / 10 h / 75 °C View Scheme
Multi-step reaction with 2 steps 1.1: isopropyl alcohol / 25 - 85 °C 2.1: trifluoroacetic acid / 24 h / 80 °C 2.2: 0.17 h View Scheme

4-hydroxythiobenzamide (25984-63-8) → ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: spirit / 2.5 h / 60 - 65 °C 2: methanesulfonic acid / 10 h / 75 °C View Scheme
Multi-step reaction with 2 steps 1.1: isopropyl alcohol / 25 - 85 °C 2.1: trifluoroacetic acid / 24 h / 80 °C 2.2: 0.17 h View Scheme
Multi-step reaction with 2 steps 1: ethanol / Reflux 2: phosphorus pentoxide View Scheme

C8H11ClO4 → ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: isopropyl alcohol / 75 °C 2.1: PPA / 75 °C 2.2: 20 °C View Scheme

4-cyanophenol (767-00-0) → ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: tetraphosphorus decasulfide / ethanol / 12 h / 70 °C 2.1: isopropyl alcohol / 3 h / 55 - 85 °C 3.1: hexamethylenetetramine / 12 h / 90 °C 3.2: 0.5 h / 75 °C View Scheme
Multi-step reaction with 3 steps 1: polyphosphoric acid / water / 40 - 80 °C 2: phosphoric acid / water; ethanol / 30 - 80 °C 3: sulfuric acid / 60 - 120 °C View Scheme
Multi-step reaction with 3 steps 1: sodium hydrogensulfide; magnesium chloride monohydrate / 3 h / 20 °C 2: PPA / 0.25 h / Microwave irradiation 3: magnesium chloride; triethylamine / tetrahydrofuran / 0.17 h / Microwave irradiation View Scheme

(2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester) (161797-99-5) + formaldehyd (50-00-0) → ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2)

Conditions	Yield
With triethylamine; magnesium chloride In tetrahydrofuran for 0.166667h; Microwave irradiation;

ethyl 2-bromoacetoacetate (84911-18-2, 609-13-2) → ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol / 2 h / Reflux 2: water; trifluoroacetic acid; acetic acid / 2.5 h / 100 °C View Scheme

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) → ethyl-2-(3-cyano-4-hydroxy phenyl)-4-methyl thiozole-5-carboxylate (161798-02-3)

Conditions	Yield
Stage #1: ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate With hydroxylamine hydrochloride In N,N-dimethyl-formamide for 0.5h; Stage #2: With acetyl chloride In N,N-dimethyl-formamide at 90℃;	99%
Stage #1: ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate With hydroxylamine hydrochloride In N,N-dimethyl-formamide for 0.5h; Stage #2: With acetyl chloride In N,N-dimethyl-formamide at 90℃;	99%
With formic acid; hydroxylamine hydrochloride; sodium acetate at 100 - 105℃; for 10h;	97.6%

Isobutyl bromide (78-77-3) + ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) → febuxostat

Conditions	Yield
With potassium carbonate; N,N-dimethyl-formamide In toluene at 105℃; for 4h;	98.71%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + allyl bromide (106-95-6) → ethyl 2-[4-(allyloxy)-3-formylphenyl]-4-methyl-1,3-thiazole-5-carboxylate

Conditions	Yield
With potassium carbonate In ethanol at 70℃; for 10h; regioselective reaction;	97%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + 2-methylpropyl phenylphosphinate (13336-52-2) → C24H28NO6PS

Conditions	Yield
With N,N'-dimethylpiperazine In tetrahydrofuran at 60℃; for 3h;	95%

2-amino-benzthiazole (136-95-8) + ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) → C21H17N3O3S2

Conditions	Yield
With acetic acid In methanol Reflux;	95%

Isobutyl bromide (78-77-3) + ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) → 2-(3-formyl-4-isobutyloxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (161798-03-4)

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 75 - 85℃; for 6h;	94.7%
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 8h;	90%
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide	90%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + propyl phenyl-H-phosphinate (6911-99-5) → C23H26NO6PS

Conditions	Yield
With N,N'-dimethylpiperazine In tetrahydrofuran at 60℃; for 3h;	94%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + isobutyl p-toluenesulfonate (4873-56-7) → 2-(3-formyl-4-isobutyloxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (161798-03-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100 - 110℃; Temperature;	92.7%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + phosphonic acid diethyl ester (762-04-9) → C18H24NO7PS

Conditions	Yield
With N,N'-dimethylpiperazine In tetrahydrofuran at 60℃; for 3h;	92%

1-bromo-butane (109-65-9) + ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) → C18H21NO4S

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80 - 100℃; for 8h;	92%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + C9H11O3P → C23H24NO7PS

Conditions	Yield
With N,N'-dimethylpiperazine In tetrahydrofuran at 60℃; for 3h;	91%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + Dimethyl phosphite (868-85-9) → C16H20NO7PS

Conditions	Yield
With N,N'-dimethylpiperazine In tetrahydrofuran at 60℃; for 3h;	89%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + C13H12ClO2P → C27H25ClNO6PS

Conditions	Yield
With N,N'-dimethylpiperazine In tetrahydrofuran at 60℃; for 3h;	89%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + 2-(2-bromoacetyl)-3H-benzo[f]chromen-3-one (88735-43-7) + thiosemicarbazide (79-19-6) → ethyl 2-(4-hydroxy-3-((2-(4-(3-oxo-3H-benzo[f]chromen-2-yl)thiazol-2-yl)hydrazono)methyl)phenyl)-4-methylthiazole-5-carboxylate

Conditions	Yield
With acetic acid In ethanol for 3h; Reflux; Green chemistry;	87%

diphenyl hydrogen phosphite (4712-55-4) + ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) → C26H24NO7PS

Conditions	Yield
With N,N'-dimethylpiperazine In tetrahydrofuran at 60℃; for 3h;	86%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + C13H12NO4P → C27H25N2O8PS

Conditions	Yield
With N,N'-dimethylpiperazine In tetrahydrofuran at 60℃; for 3h;	86%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + thiosemicarbazide (79-19-6) + para-bromophenacyl bromide (99-73-0) → ethyl 2-(3-((2-(4-(4-bromophenyl)thiazol-2-yl)hydrazono)methyl)-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate

Conditions	Yield
With acetic acid In ethanol for 3h; Reflux; Green chemistry;	86%

isobutyl methanesulfonate (16156-53-9) + ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) → 2-(3-formyl-4-isobutyloxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (161798-03-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 95 - 100℃; Temperature;	85.5%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + thiosemicarbazide (79-19-6) + 4-chlorobenzoylmethyl bromide (536-38-9) → ethyl 2-(3-((2-(4-(4-chlorophenyl)thiazol-2-yl)hydrazono)methyl)-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate

Conditions	Yield
With acetic acid In ethanol for 3h; Reflux; Green chemistry;	85%

3-bromoacetylcoumarin (29310-88-1) + ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + thiosemicarbazide (79-19-6) → ethyl 2-(4-hydroxy-3-((2-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)hydrazono)methyl)phenyl)-4-methylthiazole-5-carboxylate

Conditions	Yield
With acetic acid In ethanol for 3h; Reflux; Green chemistry;	85%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + isobutyl benzenesulfonate (24698-43-9) → 2-(3-formyl-4-isobutyloxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (161798-03-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 95 - 100℃;	84.4%

Isobutyl bromide (78-77-3) + ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) → 2-(3-cyano-4-isobutyloxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (160844-75-7)

Conditions	Yield
Stage #1: ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate With hydroxylamine hydrochloride In dimethyl sulfoxide at 40℃; for 0.5h; Stage #2: With acetyl chloride In dimethyl sulfoxide at 70 - 80℃; Stage #3: Isobutyl bromide With potassium carbonate In dimethyl sulfoxide at 20 - 80℃;	84%
Stage #1: ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate With hydroxylamine hydrochloride In dimethyl sulfoxide for 0.5h; Stage #2: With acetyl chloride In dimethyl sulfoxide at 70 - 80℃; Stage #3: Isobutyl bromide With potassium carbonate In dimethyl sulfoxide at 70 - 80℃; for 5h;	84%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + p-benzoquinone (106-51-4) → ethyl 2-(5,8-dihydroxy-9-oxo-9H-xanthen-2-yl)-4-methylthiazole-5-carboxylate

Conditions	Yield
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; cesium acetate In 1,2-dichloro-ethane at 90℃; for 16h;	84%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + thiosemicarbazide (79-19-6) + α-bromoacetophenone (70-11-1) → ethyl 2-(4-hydroxy-3-((2-(4-phenylthiazol-2-yl)hydrazono)methyl)phenyl)-4-methylthiazole-5-carboxylate

Conditions	Yield
With acetic acid In ethanol for 2h; Reflux; Green chemistry;	83%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + ethyl Phenylphosphinate (172487-18-2) → C22H24NO6PS

Conditions	Yield
With N,N'-dimethylpiperazine In tetrahydrofuran at 60℃; for 3h;	81%

ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) + 4-Nitrophenacyl bromide (99-81-0) + thiosemicarbazide (79-19-6) → ethyl 2-(3-((2-(4-(4-nitrophenyl)thiazol-2-yl)hydrazono)methyl)-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate

Conditions	Yield
With acetic acid In ethanol for 4h; Reflux; Green chemistry;	80%

dibutyl hydrogen phosphite (1809-19-4) + ethyl 2‐(3‐formyl‐4‐hydroxyphenyl)‐4‐methylthiazole‐5‐carboxylate (161798-01-2) → C22H32NO7PS

Conditions	Yield
With N,N'-dimethylpiperazine In tetrahydrofuran at 60℃; for 3h;	78%

Upstream product

• 161797-99-5 (2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester) 
• 68-12-2 N,N-dimethyl-formamide 
• 50-00-0 formaldehyd 
• 84911-18-2 ethyl 2-bromoacetoacetate 
• 100-97-0 hexamethylenetetramine 
• 399017-10-8 2-(4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylic acid ethyl ester hydrochloride 
• 25984-63-8 4-hydroxythiobenzamide 
• 609-15-4 ethyl 2-chloro-3-oxo-butyrate 
• 64-19-7 acetic acid 
• 767-00-0 4-cyanophenol 

Downstream Products

• 161798-02-3 ethyl-2-(3-cyano-4-hydroxy phenyl)-4-methyl thiozole-5-carboxylate 
• 161798-03-4 2-(3-formyl-4-isobutyloxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester 

Relevant articles and documents

Design, synthesis, cytotoxic evaluation and molecular docking studies of novel thiazolyl α-aminophosphonates

Abstract: A new class of thiazolyl α-aminophosphonate derivatives was synthesized by one-pot Kabachnik–Fields reaction of ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate with various aryl amines and diethyl phosphite under solvent-free conditions using β-cyclodextrin supported sulfonic acid (β-CD-SO3H) as an efficient, reusable and heterogeneous solid acid catalyst. The products were obtained in good to excellent yields at shorter reaction time. All the title compounds were screened for cytotoxic activity against human breast cancer (MCF-7 and MDA-MB-231), prostate cancer (DU-145) liver cancer (HepG2) and HeLa cancer cell lines using sulfarodamine-B (SRB assay). Compounds (8b, –4OMe), (8h, –4NO2) and (8j, –2I, –4CF3) showed better anticancer activity when compared with standard drug Adriamycin. Further in-silico target hunting reveals the anticancer activity of the designed compounds by inhibiting DNA topoisomerase II. Graphical abstract: [Figure not available: see fulltext.].

Method for synthesizing febuxostat and intermediate thereof

The invention relates to a method for synthesizing febuxostat and an intermediate thereof, specifically a method for synthesizing 2-(3-formyl-4-isobutoxy-phenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester. The method comprises the following steps: preparing 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate; enabling the product obtained in the step (a) to react in DMF (Dimethyl Formamide) in the presence of potassium carbonate and bromo-isobutane, adding water and ethyl acetate for extraction, concentrating to obtain an organic layer, and recrystallizing with DMF to obtain 2-(3-formyl-4-isobutoxy-phenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester. The invention also relates to 2-(3-formyl-4-isobutoxy-phenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester and 2-(3-formyl-4-hydroxyphenyl)-4-methyl-5-thiazoleethyl formate and application thereof to the preparation of febuxostat. The method of the invention has excellent performance.

New preparation method of febuxostat intermediate

The invention relates to a new preparation method of a febuxostat intermediate. The method includes: taking cheap 4-hydroxybenzaldehyde as an initial raw material, firstly preparing aldoxime from 4-hydroxybenzaldehyde and hydroxylamine hydrochloride, then adding a corresponding thio reagent, and preparing a compound 4-hydroxythiobenzamide (152A1-00) by Beckmann rearrangement reaction; utilizing one-pot process, adopting cheap 4-hydroxybenzaldehyde as an initial raw material, carrying out a series of reactions, and then performing cyclization with 2-halogenated ethyl acetoacetate to obtain ethyl 2-(4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate or different salt forms (152A2x) thereof; and using isobutyl sulfonate (152H1x) with more easily controllable quality to replace bromo-isobutane soas to prepare ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate (152A4-00). In conclusion, the method provided by the invention is more beneficial to safe, simple and cost-efficientindustrial scale preparation of the febuxostat intermediate with higher purity.