16588-75-3

Usage

Uses

Used in Polymer Production:
2-METHOXY-5-TRIFLUOROMETHYLPHENYL ISOCYANATE is used as a monomer in the production of polymers for various applications due to its reactive nature, which allows for the formation of stable polymer chains.
Used in Coatings Industry:
In the coatings industry, 2-METHOXY-5-TRIFLUOROMETHYLPHENYL ISOCYANATE is used as a component in the formulation of high-performance coatings. Its reactivity contributes to the development of coatings with enhanced properties such as durability, adhesion, and resistance to environmental factors.
Used in Adhesives:
2-METHOXY-5-TRIFLUOROMETHYLPHENYL ISOCYANATE is employed as a reactive ingredient in adhesive formulations, providing strong bonding capabilities and improved performance in various adhesive applications.
Used in Foams:
2-METHOXY-5-TRIFLUOROMETHYLPHENYL ISOCYANATE is also used in the production of foams, where its reactivity aids in the creation of stable foam structures with desirable characteristics for specific end-use applications.
It is crucial to note that due to the potential health and environmental risks associated with 2-METHOXY-5-TRIFLUOROMETHYLPHENYL ISOCYANATE, strict safety measures must be implemented during its production, handling, and use to minimize exposure and ensure the well-being of workers and the environment.

InChI:InChI=1/C9H6F3NO2/c1-15-8-3-2-6(9(10,11)12)4-7(8)13-5-14/h2-4H,1H3

Synthetic route

2-Methoxy-5-trifluoromethyl-aniline (349-65-5) + trichloromethyl chloroformate (503-38-8) → 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3)

Conditions	Yield
With N,N,N',N'-tetramethyl-1,8-diaminonaphthalene In dichloromethane at 0 - 20℃; for 1.5h;	88%
With N,N,N',N'-tetramethyl-1,8-diaminonaphthalene In dichloromethane at 0 - 20℃; for 1.5h;	88%
With N,N,N',N'-tetramethyl-1,8-diaminonaphthalene In dichloromethane at 0 - 20℃; for 1.5h;	88%

phosgene (75-44-5) + 2-Methoxy-5-trifluoromethyl-aniline (349-65-5) → 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3)

Conditions	Yield
With pyridine In diethyl ether; dichloromethane; toluene
With pyridine In dichloromethane; toluene at 0 - 20℃; for 3.5h;
With sodium hydrogencarbonate In dichloromethane; water at 0℃; for 0.5h;

4-(4-acetylphenoxy)-5-aminopyridine (284670-99-1) + 2-Methoxy-5-trifluoromethyl-aniline (349-65-5) → 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3)

2-Methoxy-5-trifluoromethyl-aniline (349-65-5) + N,N,N',N'-tetramethyl-1,8-diaminonaphthalene (20734-58-1) + trichloromethyl chloroformate (503-38-8) → 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3)

Conditions	Yield
In dichloromethane

bis(trichloromethyl) carbonate (32315-10-9) + 2-Methoxy-5-trifluoromethyl-aniline (349-65-5) → 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3)

Conditions	Yield
With pyrographite In ethyl acetate for 2h; Reflux;

5-(4-aminophenoxy)isoindoline-1,3-dione (284462-39-1) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) → N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(1,3-dioxoisoindolin-5-yloxy)phenyl)urea

Conditions	Yield
In dichloromethane at 0 - 20℃; for 12 - 22h; Product distribution / selectivity;	96%

2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) + 2-bromo-6-fluoroaniline (65896-11-9) → 3-(2-bromo-6-fluorophenyl)-1-[2-methoxy-5-(trifluoromethyl)phenyl]urea (917389-23-2)

Conditions	Yield
In acetonitrile at 35 - 88℃; for 38 - 45h; Product distribution / selectivity;	87.5%

2-Fluoroaniline (348-54-9) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) → N-(2-fluorophenyl)-N'-[2-methoxy-5-(trifluoromethyl)phenyl]urea (917389-24-3)

Conditions	Yield
In acetonitrile at 82℃; for 4h;	86.4%
In acetonitrile for 4h; Reflux; Large scale;	85.9%
In acetonitrile at 0℃; for 7.25h; Reflux; Large scale;	85.9%
In acetonitrile for 4h; Reflux; Large scale;	85.9%
In acetonitrile Reflux;

N-(4-fluoro-3-methylphenyl)-piperazine (140479-05-6) + (2E)-3-{3-fluoro-2-[(triphenylphosphoranylidene)amino]phenyl}-propenoic acid methyl ester (791117-28-7) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) → {8-fluoro-2-[4-(4-fluoro-3-methylphenyl)-1-piperazinyl]-3-[6-methoxy-3-(trifluoro-methyl)phenyl]-3,4-dihydro-4-quinazolinyl}-acetic acid methyl ester

Conditions	Yield
	79%

(2E)-3-{3-fluoro-2-[(triphenylphosphoranylidene)amino]phenyl}-propenoic acid methyl ester (791117-28-7) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) → methyl (2E)-3-(3-fluoro-2-((((2-methoxy-5-(trifluoromethyl)phenyl)imino)methylene)amino)phenyl)acrylate

Conditions	Yield
In dichloromethane at 20℃;	62%

2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) + 3-chloro-aniline (108-42-9) → 1-(3-chlorophenyl)-3-(2-methoxy-5-(trifluoromethyl)phenyl)urea

Conditions	Yield
In dichloromethane at 0℃; for 0.75h;	55%

9-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole (796069-32-4) + (2E)-3-{3-fluoro-2-[(triphenylphosphoranylidene)amino]phenyl}-propenoic acid methyl ester (791117-28-7) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) → [8-fluoro-3-(2-methoxy-5-trifluoromethyl-phenyl)-2-(9-methyl-3,4-dihydro-1H-pyrazino[1,2-a]indol-2-yl)-3,4-dihydro-quinazolin-4-yl]acetic acid methyl ester (796069-35-7)

Conditions	Yield
Stage #1: (2E)-3-{3-fluoro-2-[(triphenylphosphoranylidene)amino]phenyl}-propenoic acid methyl ester; 2-methoxy-5-trifluoromethylphenyl isocyanate In dichloromethane at 20℃; Stage #2: 9-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole With silica gel In 1,4-dioxane; dichloromethane at 20℃; Heating / reflux;	42%

2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) + (2E)-3-{2-[(triphenylphosphoranylidene)amino]phenyl}-propenoic acid methyl ester (138386-58-0) → (2E)-3-{2-[(iminomethylen)amino]phenyl}-acrylic acid methyl ester-1-methoxy-4-(trifluoromethyl)-benzene

Conditions	Yield
In dichloromethane at 20℃;	38%

2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) + 4-fluoroaniline (371-40-4) → N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-fluorophenyl)urea

Conditions	Yield
In ethyl acetate
In ethyl acetate at 20℃; for 72h;
In ethyl acetate at 20℃; for 72h;
In ethyl acetate at 20℃; for 72h; Product distribution / selectivity;

C19H23N5O + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) → 1-{4-[2-(2-dimethylamino-ethylamino)-6-methyl-pyrimidin-4-yloxy]-naphthalen-1-yl}-3-(2-methoxy-5-trifluoromethyl-phenyl)-urea

Conditions	Yield
In tetrahydrofuran at 20℃;

C20H22N4O2 + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) → 1-(2-methoxy-5-trifluoromethyl-phenyl)-3-[4-(6-methyl-2-morpholin-4-ylmethyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-urea

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃;

3-(2-pyridin-4-yl-imidazol-1-ylmethyl)-phenylamine + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) → 1-(2-methoxy-5-trifluoromethyl-phenyl)-3-[3-(2-pyridin-4-yl-imidazol-1-ylmethyl)-phenyl]-urea

Conditions	Yield
In dichloromethane; N,N-dimethyl-formamide

4-(4-acetylphenoxy)-5-aminopyridine (284670-99-1) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) + 4-Fluoronitrobenzene (350-46-9) + 4-Hydroxyacetophenone (99-93-4) → 1-(4-(4-nitrophenoxy)phenyl)ethanone (75919-92-5)

4-chloro-pyridine-2-carbonyl chloride (53750-66-6) + 3-(4-(2-(N-methylcarbamoyl)phenylthio)aniline + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) + 2-Methoxy-5-trifluoromethyl-aniline (349-65-5) + isopropylamine (75-31-0) → 4-(2-(N-isopropylcarbamoyl)-pyridin-4-yloxy)aniline (284462-89-1) + 4-amino-phenol (123-30-8)

4-(4-(2-(N-methylcarbamoyl)phenylthio)aniline + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) + 2-Methoxy-5-trifluoromethyl-aniline (349-65-5) → 5-(4-aminophenoxy)-2-methylisoindoline-1,3-dione

4-(4-amino-3-chloro-phenoxy)-pyridine-2-carboxylic acid methylamide (284462-44-8) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) + amino-4 hydroxy-2 toluene (2835-95-2) + 2-Methoxy-5-trifluoromethyl-aniline (349-65-5) → 3-(2-(N-methylcarbamoyl)-pyridin-4-yloxy)-4-methylaniline (284462-92-6) + 4-chloro-N-methylpicolinamide (220000-87-3)

4-(4-aminophenoxy)-N,N-dimethylpicolinamide (284462-86-8) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) + 2-Methoxy-5-trifluoromethyl-aniline (349-65-5) → 4-(1-oxoisoindolin-5-yloxy)aniline (284462-54-0)

4-(2-(N-isopropylcarbamoyl)-pyridin-4-yloxy)aniline (284462-89-1) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) + 2-Methoxy-5-trifluoromethyl-aniline (349-65-5) → methyl 5-(4-aminophenoxy)pyridine-3-carboxylate (284462-58-4)

N-methylphthalimide (550-44-7) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) + 2-Methoxy-5-trifluoromethyl-aniline (349-65-5) → 4-chloro-N-methylpicolinamide (220000-87-3)

5-methyl-1-(pyridin-4-yl)methyl-1H-benzimidazol-4-ylamine (915295-45-3) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) → 1-(2-Methoxy-5-trifluoromethyl-phenyl)-3-(5-methyl-1-pyridin-4-ylmethyl-1H-benzoimidazol-4-yl)-urea

Conditions	Yield
In dichloromethane for 4h;

1-(Pyridin-4-yl)methyl-1H-benzimidazol-4-ylamine (915295-51-1) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) → 1-(2-Methoxy-5-trifluoromethyl-phenyl)-3-(1-pyridin-4-ylmethyl-1H-benzoimidazol-4-yl)-urea

Conditions	Yield
In dichloromethane; N,N-dimethyl-formamide at 20℃; for 16h;

6-(3-aminophenyl)-N-(pyridin-4-ylmethyl)imidazo[1,2-a]pyrazin-8-amine (1044656-17-8) + 2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) → 1-(2-metoxy-5-trifluoromethyl-phenyl)-3-(3-{8-[(-pyridin-4-yl-methyl)-amino]-imidazo[1,2-a]pyrazin-6-yl}-phenyl)-urea (847024-36-6)

Conditions	Yield
In toluene at 20℃; for 0.5h;

2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) + 4-(2-aminoethyl)-2-nitro-phenylamine (159417-93-3) → C17H17F3N4O4 (863910-65-0)

Conditions	Yield
In dichloromethane at 20℃; for 2h;

2-methoxy-5-trifluoromethylphenyl isocyanate (16588-75-3) → (S)-2-(8-fluoro-3-(2-methoxy-5-(trifluoromethyl)-phenyl)-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3,4-dihydroquinazolin-4-yl)acetic acid (917389-32-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: acetonitrile / Reflux 2: acetic acid; palladium diacetate 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetone / Reflux 4: 1,8-diazabicyclo[5.4.0]undec-7-ene; trichlorophosphate / chlorobenzene / Reflux 5: 1,8-diazabicyclo[5.4.0]undec-7-ene / 1,4-dioxane / Reflux 6: ethyl acetate / 20 °C 7: sodium hydrogencarbonate; sodium hydroxide; water / tert-butyl methyl ether / Reflux; Large scale View Scheme
Multi-step reaction with 6 steps 1.1: acetonitrile / 4 h / Reflux; Large scale 2.1: acetic acid; sulfuric acid; sulfur trioxide; palladium diacetate; oxygen / 20 h / 20 °C / Inert atmosphere; Large scale 3.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetone / 4 h / Reflux; Large scale 4.1: trichlorophosphate / chlorobenzene / 3 h / Reflux; Large scale 4.2: 9 h / Reflux; Large scale 5.1: ethyl acetate / 1 h / 20 °C / Large scale 5.2: 72 h / 20 °C / Large scale 6.1: sodium hydrogencarbonate / water; tert-butyl methyl ether / Large scale 6.2: Reflux; Large scale View Scheme
Multi-step reaction with 7 steps 1.1: acetonitrile / 7.25 h / 0 °C / Reflux; Large scale 2.1: acetic acid / Inert atmosphere; Large scale 2.2: 20 h / 20 °C / Inert atmosphere; Large scale 3.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetone / 4 h / 55 °C / Reflux; Large scale 4.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; trichlorophosphate / chlorobenzene / 12 h / Reflux; Large scale 5.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / 1,4-dioxane / 4 h / Reflux; Large scale 6.1: ethyl acetate / 76 h / 0 - 20 °C / Large scale 7.1: sodium hydrogencarbonate; water; sodium hydroxide / tert-butyl methyl ether / 22 °C / Reflux; Large scale View Scheme

Upstream product

• 75-44-5 phosgene 
• 349-65-5 2-Methoxy-5-trifluoromethyl-aniline 
• 503-38-8 trichloromethyl chloroformate 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 20734-58-1 N,N,N',N'-tetramethyl-1,8-diaminonaphthalene 
• 284670-99-1 4-(4-acetylphenoxy)-5-aminopyridine 

Downstream Products

• 284462-92-6 3-(2-(N-methylcarbamoyl)-pyridin-4-yloxy)-4-methylaniline 
• 220000-87-3 4-chloro-N-methylpicolinamide 
• 284462-54-0 4-(1-oxoisoindolin-5-yloxy)aniline 
• 284462-58-4 methyl 5-(4-aminophenoxy)pyridine-3-carboxylate 
• 796069-35-7 [8-fluoro-3-(2-methoxy-5-trifluoromethyl-phenyl)-2-(9-methyl-3,4-dihydro-1H-pyrazino[1,2-a]indol-2-yl)-3,4-dihydro-quinazolin-4-yl]acetic acid methyl ester 
• 847024-36-6 1-(2-metoxy-5-trifluoromethyl-phenyl)-3-(3-{8-[(-pyridin-4-yl-methyl)-amino]-imidazo[1,2-a]pyrazin-6-yl}-phenyl)-urea 
• 330796-28-6 2-{1-[N-(2-methoxy-5-trifluoromethylphenylcarbamoyl)-N-methylamino]ethyl}-3-(4'-fluorophenyl)quinazolin-4-one 
• 917389-35-6 [(R)-8-fluoro-2-[4-(3-methoxy-phenyl)-piperazin-1-yl]-3-(2-methoxy-5-trifluoromethyl-phenyl)-3,4-dihydro-quinazolin-4-yl]-acetic acid methyl ester (2R,3R)-2,3-bis-(4-methyl-benzoyloxy)-succinic acid salt 
• 917389-26-5 methyl-(E)-3-(3-fluoro-2-(3-(2-methoxy-5-(trifluoromethyl)phenyl)ureido)phenyl)acrylate 
• 917389-34-5 (R)-methyl 2-(8-fluoro-3-(2-methoxy-5-(trifluoromethyl)phenyl)-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3,4-dihydroquinazolin-4-yl)acetate 
• 917389-37-8 (R)-2-(8-fluoro-3-(2-methoxy-5-(trifluoromethyl)phenyl)-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3,4-dihydroquinazolin-4-yl)acetic acid 
• 917389-32-3 (S)-2-(8-fluoro-3-(2-methoxy-5-(trifluoromethyl)-phenyl)-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3,4-dihydroquinazolin-4-yl)acetic acid 
• 791116-51-3 (+/-)-{8-fluoro-2-[4-(3-methoxyphenyl)-piperazin-1-yl]-3-[2-methoxy-5-trifluoromethyl-phenyl]-3,4-dihydro-quinazolin-4-yl}acetic acid 

Relevant academic research and scientific papers

Mediators of hedgehog signaling pathways, compositions and uses related thereto

The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function by contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize hedgehog activity.

Inhibition Of Raf Kinase Using Symmetrical And Unsymmetrical Substituted Diphenyl Ureas

This invention relates to the use of a group of aryl ureas in treating raf mediated diseases, and pharmaceutical compositions for use in such therapy.

2-(3-Phenyl-2-piperazinyl-3,4-dihydroquinazolin-4-yl)acetic acids as antiviral agents, especially against cytomegaloviruses

The invention relates to dihydroquinazolines and methods for the production thereof, the use thereof in the treatment and/or prophylaxis of diseases, in addition to the use thereof in the production of medicaments in the treatment and/or prophylaxis of diseases, especially for use as anti-viral agents, especially against cytomegalo viruses.

SUBSTITUTED AZACHINAZOLINES HAVING AN ANTIVIRAL ACTION

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SUBSTITUTED DIHYDROCHINAZOLINES HAVING ANTIVIRAL PROPERTIES

The invention relates to substituted dihydrochinazolines of formula (I), methods for the production thereof, and the use thereof for producing medicaments used for treating and/or preventing diseases, particularly as antiviral agents, especially against cytomegaloviruses.

2-(3-PHENYL-2-PIPERAZINYL-3,4-DIHYDROQUINAZOLINE-4-YL) ACETIC ACIDS AS ANTI-VIRAL AGENTS, ESPECIALLY AGAINST CYTOMEGALO VIRUSES

The invention relates to dihydroquinazolines and methods for the production thereof, the use thereof in the treatment and/or prophylaxis of diseases, in addition to the use thereof in the production of medicaments in the treatment and/or prophylaxis of diseases, especially for use as anti-viral agents, especially against cytomegalo viruses.

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