170569-88-7

Basic information

• Product Name: 4-[5-(4-FLUOROPHENYL)-3-(TRIFLUOROMETHYL)PYRAZOL-1-YL]BENZENE-1-SULFONAMIDE
• Synonyms: 4-[5-(4-FLUOROPHENYL)-3-(TRIFLUOROMETHYL)PYRAZOL-1-YL]BENZENE-1-SULFONAMIDE;Mavacoxib;BenzenesulfonaMide, 4-[5-(4-fluorophenyl)-3-(trifluoroMethyl)-1H-pyrazol-1-yl]-;4-[5-(4-Fluorophenyl)-3-trifluoroMethyl-1H-pyrazol-1-yl] benzenesulfonaMide;Trocoxil;PHA 739521;4-[5-(4-Fluoro-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-benzenesulfonamide
• CAS NO: 170569-88-7
• Molecular Formula: C₁₆H₁₁F₄N₃O₂S
• Molecular Weight: 385.34
• Product Categories: Aromatics, Heterocycles, Inhibitors, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 170569-88-7.mol

Chemical Properties

• Boiling Point: 519.8±60.0 °C(Predicted)
• Appearance: /
• Density: 1.51±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 9.67±0.10(Predicted)
• CAS DataBase Reference: 4-[5-(4-FLUOROPHENYL)-3-(TRIFLUOROMETHYL)PYRAZOL-1-YL]BENZENE-1-SULFONAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-[5-(4-FLUOROPHENYL)-3-(TRIFLUOROMETHYL)PYRAZOL-1-YL]BENZENE-1-SULFONAMIDE(170569-88-7)
• EPA Substance Registry System: 4-[5-(4-FLUOROPHENYL)-3-(TRIFLUOROMETHYL)PYRAZOL-1-YL]BENZENE-1-SULFONAMIDE(170569-88-7)

Safety Data

• Hazardous Substances Data: 170569-88-7(Hazardous Substances Data)

Usage

InChI:InChI=1/C16H11F4N3O2S/c17-11-3-1-10(2-4-11)14-9-15(16(18,19)20)22-23(14)12-5-7-13(8-6-12)26(21,24)25/h1-9H,(H2,21,24,25)

Synthetic route

N,N-dibenzyl-4-(5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide → mavacoxib (170569-88-7)

Conditions	Yield
With sulfuric acid at 20℃; for 8h;	99%

5-(4-fluorophenyl)-3-(trifluoromethyl)isoxazole (70862-56-5) + 4-hydrazinobenzene-1-sulfonamide hydrochloride (17852-52-7, 27918-19-0) → mavacoxib (170569-88-7)

Conditions	Yield
With acetic acid In ethanol at 80℃; for 10h; regioselective reaction;	95%

1-(4-fluorophenyl)-4,4,4-trifluoro-1,3-butanedione (582-65-0) + 4-hydrazinobenzene-1-sulfonamide hydrochloride (17852-52-7, 27918-19-0) → mavacoxib (170569-88-7)

Conditions	Yield
In methanol; water at 120℃; under 24002.4 Torr; for 0.221667h; Flow reactor;	82%
In ethanol for 20h; Heating; Yield given;
In ethanol for 20h; Heating / reflux;

ethyl trifluoroacetate, (383-63-1) + 1-(4-fluorophenyl)ethanone (403-42-9) + 4-hydrazinobenzene-1-sulfonamide hydrochloride (17852-52-7, 27918-19-0) → mavacoxib (170569-88-7)

Conditions	Yield
Stage #1: ethyl trifluoroacetate,; 1-(4-fluorophenyl)ethanone; 4-hydrazinobenzene-1-sulfonamide hydrochloride With hydrogenchloride; sodium methylate In methanol; isopropyl alcohol at 55℃; for 2h; Stage #2: 4-hydrazinobenzene-1-sulfonamide hydrochloride With hydrogenchloride In water; isopropyl alcohol at 20 - 70℃; for 8h;	80%
Stage #1: ethyl trifluoroacetate,; 1-(4-fluorophenyl)ethanone With sodium methylate In methanol; isopropyl alcohol at 55℃; for 2.25h; Stage #2: 4-hydrazinobenzene-1-sulfonamide hydrochloride With trifluoroacetic acid In methanol; isopropyl alcohol at 20 - 55℃; for 11h; Stage #3: With sodium hydroxide In methanol; water; isopropyl alcohol pH=6 - 7;

N,N-dibenzyl-4-iodobenzenesulfonamide (428486-70-8) + 5-(4-fluoridophenyl)-3-(trifluoridomethyl)-1H-pyrazole → mavacoxib (170569-88-7)

Conditions	Yield
Stage #1: N,N-dibenzyl-p-iodobenzenesulfonamide; 5-(4-fluoridophenyl)-3-(trifluoridomethyl)-1H-pyrazole With copper(l) iodide; potassium carbonate; cis-N,N'-dimethyl-1,2-diaminocyclohexane In 1,4-dioxane at 150℃; for 24h; Microwave irradiation; Inert atmosphere; Stage #2: With sulfuric acid at 20℃; for 4h; Microwave irradiation; Inert atmosphere;	43%

1-(4-fluorophenyl)ethanone (403-42-9) → mavacoxib (170569-88-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaOMe / methanol / 24 h / Heating 2: ethanol / 20 h / Heating View Scheme
Multi-step reaction with 2 steps 1: sodium hydride / tetrahydrofuran 2: hydrogenchloride / ethanol / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 1.2: 12 h / 0 - 25 °C 2.1: methanol; water / 0.22 h / 120 °C / 24002.4 Torr / Flow reactor View Scheme

4-(5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide (170569-87-6) → mavacoxib (170569-88-7)

1-(4-fluorophenyl)-4,4,4-trifluoro-1,3-butanedione (582-65-0) + 4-aminosulfonylphenylhydrazine (4392-54-5) → mavacoxib (170569-88-7)

Conditions	Yield
With hydrogenchloride In ethanol Reflux;

4-fluorobenzaldehyde (459-57-4) → mavacoxib (170569-88-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: acetic acid; piperidine / benzene / 26 h / 0 - 20 °C 2: toluene-4-sulfonic acid hydrazide; sodium acetate / ethanol / 12 h / 80 °C / Schlenk technique 3: copper(l) iodide; potassium carbonate; cis-N,N'-dimethyl-1,2-diaminocyclohexane / 1,4-dioxane / 150 °C / Schlenk technique; Inert atmosphere 4: sulfuric acid / 8 h / 20 °C View Scheme

(E)-1,1,1-trifluoro-4-(4-fluorophenyl)but-3-en-2-one (101048-46-8) → mavacoxib (170569-88-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid hydrazide; sodium acetate / ethanol / 12 h / 80 °C / Schlenk technique 2: copper(l) iodide; potassium carbonate; cis-N,N'-dimethyl-1,2-diaminocyclohexane / 1,4-dioxane / 150 °C / Schlenk technique; Inert atmosphere 3: sulfuric acid / 8 h / 20 °C View Scheme

4-iodobenzenesulfonyl chloride (98-61-3) → mavacoxib (170569-88-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane / 0.11 h / 80 °C / 6723.1 Torr 2.1: cis-N,N'-dimethyl-1,2-diaminocyclohexane; copper(l) iodide; potassium carbonate / 1,4-dioxane / 24 h / 150 °C / Microwave irradiation; Inert atmosphere 2.2: 4 h / 20 °C / Microwave irradiation; Inert atmosphere View Scheme

sulfanilamide (63-74-1) → mavacoxib (170569-88-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium nitrite; hydrogenchloride / water / 0.25 h / Cooling with ice 1.2: 1 h / 0 °C 2.1: methanol; water / 0.22 h / 120 °C / 24002.4 Torr / Flow reactor View Scheme

mavacoxib (170569-88-7) + methyl iodide (74-88-4) → methanesulfonamide (3144-09-0) + 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-N-methylbenzenesulfonamide

Conditions	Yield
In dimethyl sulfoxide	A n/a B 21%

mavacoxib (170569-88-7) + methyl iodide (74-88-4) → 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-N-methylbenzenesulfonamide + 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-N,N-dimethylbenzenesulfonamide

Conditions	Yield
With sodium hydride; dimethyl sulfoxide 1.) RT, 1.5 h, 2.) RT, 16 h; Yield given. Multistep reaction. Yields of byproduct given;

PEG 1000 + mavacoxib (170569-88-7) → Reaxys ID: 12561236

Conditions	Yield
In ethanol at 20℃;

mavacoxib (170569-88-7) + PEG 400 → Reaxys ID: 15739273

Conditions	Yield
In ethanol at 20℃; Product distribution / selectivity;
In water for 336h; Product distribution / selectivity;

PEG 600 + mavacoxib (170569-88-7) → Reaxys ID: 12561237

Conditions	Yield
In ethanol at 20℃;

mavacoxib (170569-88-7) → C16H7(2)H4F4N3O2S

Conditions	Yield
With ((CH3)2C3N2(C6H2(CH3)3)2)Ir(C8H12)Cl; deuterium In dichloromethane at 25℃; for 2h; Reagent/catalyst; chemoselective reaction;

Upstream product

• 582-65-0 1-(4-fluorophenyl)-4,4,4-trifluoro-1,3-butanedione 
• 17852-52-7 4-hydrazinobenzene-1-sulfonamide hydrochloride 
• 403-42-9 1-(4-fluorophenyl)ethanone 
• 383-63-1 ethyl trifluoroacetate, 
• 70862-56-5 5-(4-fluorophenyl)-3-(trifluoromethyl)isoxazole 
• 63-74-1 sulfanilamide 
• 428486-70-8 N,N-dibenzyl-p-iodobenzenesulfonamide 
• 98-61-3 p-Iodobenzenesulfonyl chloride 
• 101048-46-8 (E)-1,1,1-trifluoro-4-(p-fluorophenyl)-3-buten-1-one 
• 459-57-4 4-fluorobenzaldehyde 
• 4392-54-5 4-aminosulfonylphenylhydrazine 
• 170569-87-6 4-(5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide 

Downstream Products

• 3144-09-0 methanesulfonamide 

Relevant articles and documents

Radical Decarboxylative Carbometalation of Benzoic Acids: A Solution to Aromatic Decarboxylative Fluorination

Abundant aromatic carboxylic acids exist in great structural diversity from nature and synthesis. To date, the synthetically valuable decarboxylative functionalization of benzoic acids is realized mainly by transition-metal-catalyzed decarboxylative cross couplings. However, the high activation barrier for thermal decarboxylative carbometalation that often requires 140 °C reaction temperature limits both the substrate scope as well as the scope of suitable reactions that can sustain such conditions. Numerous reactions, for example, decarboxylative fluorination that is well developed for aliphatic carboxylic acids, are out of reach for the aromatic counterparts with current reaction chemistry. Here, we report a conceptually different approach through a low-barrier photoinduced ligand to metal charge transfer (LMCT)-enabled radical decarboxylative carbometalation strategy, which generates a putative high-valent arylcopper(III) complex, from which versatile facile reductive eliminations can occur. We demonstrate the suitability of our new approach to address previously unrealized general decarboxylative fluorination of benzoic acids.

Copper-Catalyzed Reductive Ring-Cleavage of Isoxazoles: Synthesis of Fluoroalkylated Enaminones and Application for the Preparation of Celecoxib, Deracoxib, and Mavacoxib

We have identified a new reactivity of copper/diamine catalysis for the reductive ring-cleavage of isoxazoles to yield fluoroalkylated enaminones. This protocol has the advantage of using commercially available reagents, ease of setting up, broad tolerance of functionality, and is regiospecific and free of defluorination and reduction of reducible functional groups. The utility was demonstrated by a one-step, regioselective synthesis of fluoroalkylated pyrazole-based drugs such as celecoxib, deracoxib, and mavacoxib.

A CONTINUOUS FLOW MICRO-TOTAL PROCESS SYSTEM FOR PREPARATION OF CELECOXIB AND ANALOGS THEREOF

The present invention relates to preparation of pyrazoles. This invention further relates to a continuous flow micro-total process system for preparation of celecoxib, a COX-2 selective non-steroidal anti-inflammatory drug, and analogs thereof.

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Crystalline pyrazoles

The present invention relates to crystal forms of 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide and methods for preparation, interconversion, and isolation of such crystals.

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