35277-02-2

Basic information

• Product Name: 4-Fluoro-1H-pyrazole
• Synonyms: 4-Fluoro-1H-pyrazole;4-Fluoro-1H-pyrazole4-Fluoro-1H-pyrazole
• CAS NO: 35277-02-2
• Molecular Formula: C₃H₃FN₂
• Molecular Weight: 86.07
• Mol File: 35277-02-2.mol
• Article Data: 12

Chemical Properties

• Boiling Point: 193℃
• Flash Point: 70℃
• Appearance: /
• Density: 1.320
• Vapor Pressure: 0.673mmHg at 25°C
• Refractive Index: 1.487
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• PKA: 13.66±0.50(Predicted)
• CAS DataBase Reference: 4-Fluoro-1H-pyrazole(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Fluoro-1H-pyrazole(35277-02-2)
• EPA Substance Registry System: 4-Fluoro-1H-pyrazole(35277-02-2)

Safety Data

• Hazardous Substances Data: 35277-02-2(Hazardous Substances Data)

Usage

Description

4-Fluoro-1H-pyrazole is an organic compound with the molecular formula C4H3FN2. It is a derivative of the pyrazole ring, which is a five-membered heterocyclic compound containing two nitrogen atoms. The presence of a fluorine atom at the 4-position of the pyrazole ring imparts unique chemical and electronic properties to the molecule, making it a versatile building block in organic synthesis and a potential candidate for various applications in the pharmaceutical and chemical industries.

Uses

Used in Pharmaceutical Industry:
4-Fluoro-1H-pyrazole is used as an intermediate in the synthesis of various pharmaceutical compounds. Its unique chemical properties, such as the presence of the fluorine atom and the pyrazole ring, make it a valuable building block for the development of new drugs with improved pharmacological profiles.
Used in Chemical Synthesis:
4-Fluoro-1H-pyrazole is used as a key intermediate in the preparation of various organic compounds, particularly those with potential applications in the chemical industry. Its reactivity and stability make it a suitable candidate for use in a wide range of synthetic reactions, including cross-coupling reactions and other C-C bond-forming processes.
Used in Palladium-Catalyzed Cross-Coupling Reactions:
4-Fluoro-1H-pyrazole is used as a reactant in palladium-catalyzed cross-coupling reactions, which are widely employed in the synthesis of complex organic molecules. The presence of the fluorine atom at the 4-position of the pyrazole ring allows for selective functionalization and the formation of new C-C bonds, leading to the creation of diverse molecular structures with potential applications in various fields.
Used in the Preparation of Tributylstannyl Fluoropyrazole:
4-Fluoro-1H-pyrazole is used in the preparation of tributylstannyl fluoropyrazole, which is a valuable reagent in organic synthesis. The stannyl group (Bu3Sn) provides a handle for further functionalization and can be used in various cross-coupling reactions, enabling the formation of new C-C, C-N, and C-O bonds, among others. This reagent can be employed in the synthesis of a wide range of organic compounds, including pharmaceuticals, agrochemicals, and advanced materials.

InChI:InChI=1/C3H3FN2/c4-3-1-5-6-2-3/h1-2H,(H,5,6)

Synthetic route

fluoro(trimethylsilyl)acetylene (38346-22-4) → 4-fluoro-1H-pyrazole (35277-02-2)

Conditions	Yield
With tetrabutyl ammonium fluoride; acetic acid In tetrahydrofuran at 50℃;	84%

(Z)-3-(dimethylamino)-2-fluoroacrylaldehyde (761-88-6) → 4-fluoro-1H-pyrazole (35277-02-2)

Conditions	Yield
With hydrazine dihydrochloride In ethanol; water at 55℃; for 0.5h;	77%
With hydrazine dihydrochloride In ethanol; water at 55℃; for 0.5h;	77%

4-fluoro-5-(tributylstannyl)-1H-pyrazole (853180-40-2) → 4-fluoro-1H-pyrazole (35277-02-2)

Conditions	Yield
Stage #1: 4-fluoro-5-(tributylstannyl)-1H-pyrazole With n-butyllithium In tetrahydrofuran at -78℃; Stage #2: With oxonium In tetrahydrofuran Further stages.;	68%

β-(Diethylamino)-α-fluoropropenal (139680-79-8) → 4-fluoro-1H-pyrazole (35277-02-2)

Conditions	Yield
Stage #1: β-(Diethylamino)-α-fluoropropenal With hydrazine dihydrochloride In ethanol; water at 78℃; for 4h; Stage #2: With sodium hydrogencarbonate In ethanol; water at 20℃; pH=7;	61%

ethanol (64-17-5) + 7-chloro-7-fluoro-2,5-dioxabicyclo<4.1.0>heptane (40623-35-6, 40623-36-7, 120201-74-3) → 4-fluoro-1H-pyrazole (35277-02-2)

Conditions	Yield
With hydrazine dihydrochloride; sulfuric acid; water 1.) reflux, 7 d, 2.) EtOH, reflux, 2 h; Yield given. Multistep reaction;

(2,3,3-Trifluoro-1-propenyl)trimethylammonium Iodide (128229-03-8) + diethylamine (109-89-7) → 4-fluoro-1H-pyrazole (35277-02-2)

Conditions	Yield
With hydrazine hydrochloride 1.) 65-70 deg C, 1 h, MeCN; 2.) 50-60 deg C, MeCN,; Yield given. Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + Vinylidene fluoride (75-38-7) → 4-fluoro-1H-pyrazole (35277-02-2)

Conditions	Yield
Multistep reaction;

β-(Dimethylamino)-α-fluoropropenal (761-88-6) → 4-fluoro-1H-pyrazole (35277-02-2)

Conditions	Yield
With hydrazine dihydrochloride In ethanol; water at 55℃; for 0.333333h;	366 mg

tert-butyl 4-((7-(3-bromophenyl)-6-chloro-4-oxo-4, 7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl)methyl)-4-hydroxypiperidine-1-carboxylate + 4-fluoro-1H-pyrazole (35277-02-2) → tert-butyl 4-((6-chloro-7-(3-(4-fluoro-1H-pyrazol-1-yl)phenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl)methyl)-4-hydroxypiperidine-1-carboxylate

Conditions	Yield
With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; copper(l) iodide; potassium carbonate In N,N-dimethyl-formamide at 110℃; for 4h; Sealed tube; Inert atmosphere;	99%

4-fluoro-1H-pyrazole (35277-02-2) + 1-(6-bromopyridin-3-yl)ethanone (139042-59-4) → 1-(6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl)ethane-1-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 20h;	96%
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 20h; Sealed tube;	96%
Stage #1: 4-fluoro-1H-pyrazole With potassium carbonate In N,N-dimethyl-formamide for 0.166667h; Stage #2: 1-(6-bromopyridin-3-yl)ethanone In N,N-dimethyl-formamide at 100℃; for 20h; Sealed tube;	96%

2-(bromomethyl)-1-fluoro-3-iodobenzene (1231747-49-1) + 4-fluoro-1H-pyrazole (35277-02-2) → C10H7F2IN2 (1231747-27-5)

Conditions	Yield
With sodium hydride In tetrahydrofuran Reflux;	95%

1-(5-chloropyrazin-2-yl)ethan-1-one (160252-31-3) + 4-fluoro-1H-pyrazole (35277-02-2) → 1-(5-(4-fluoro-1H-pyrazol-1-yl)pyrazin-2-yl)ethan-1-one

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.166667h;	95%
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.166667h;	95%
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.166667h;	95%
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.166667h;	95%

3,4-dihydro-2H-pyran (110-87-2) + 4-fluoro-1H-pyrazole (35277-02-2) → 4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole

Conditions	Yield
With trifluoroacetic acid In tetrahydrofuran Reflux;	93%
With trifluoroacetic acid In tetrahydrofuran Reflux;	93%

2-bromo-4'-methylpropiophenone (92821-88-0, 1451-82-7) + 4-fluoro-1H-pyrazole (35277-02-2) → 2-(4-fluoro-1H-pyrazol-1-yl)-1-(4-methylphenyl)propan-1-one

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃;	91%

4-fluoro-1H-pyrazole (35277-02-2) + N-[4-cyano-3-(trifluoromethyl)phenyl]-2-methyloxirane-2-carboxamide (90357-51-0) → N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-fluoro-1H-pyrazol-1-yl)-2-hydroxy-2-methylpropanamide

Conditions	Yield
Stage #1: 4-fluoro-1H-pyrazole With sodium hydride In tetrahydrofuran; mineral oil for 3h; Inert atmosphere; Cooling with ice; Stage #2: N-[4-cyano-3-(trifluoromethyl)phenyl]-2-methyloxirane-2-carboxamide In tetrahydrofuran; mineral oil at 20℃; Inert atmosphere;	90%

4-fluoro-1H-pyrazole (35277-02-2) + Bromoacetaldehyde diethyl acetal (2032-35-1) → 1-(2,2-diethoxyethyl)-4-fluoro-1H-pyrazole

Conditions	Yield
With caesium carbonate In acetonitrile at 20 - 82℃; for 16h; Inert atmosphere;	89%

tert-butyl 3-bromo-1-oxa-8-azaspiro[4.5]decane-8-carboxylate (898157-46-5) + 4-fluoro-1H-pyrazole (35277-02-2) → tert-butyl 3-(4-fluoro-1H-pyrazol-1-yl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 2h; Inert atmosphere;	89%

7-bromo-5-(chloromethyl)-2,3-dihydro-1-benzofuran + 4-fluoro-1H-pyrazole (35277-02-2) → 1-[(7-bromo-2,3-dihydro-1-benzofuran-5-yl)methyl]-4-fluoro-1H-pyrazole

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18h;	88%

4-fluoro-1H-pyrazole (35277-02-2) + 2-(tert-butyldimethylsilyloxy)ethyl bromide (86864-60-0) → 1-{2-[(tert-butyldimethylsilyl)oxy]ethyl}-4-fluoro-1H-pyrazole

Conditions	Yield
With caesium carbonate In acetonitrile at 20℃; for 16h; Cooling with ice; Inert atmosphere; regioselective reaction;	87%

tert-butyl (3S)-3-{[(4-methylphenyl)sulfonyl]oxy}-1-oxa-8-azaspiro[4.5]decane-8-carboxylate + 4-fluoro-1H-pyrazole (35277-02-2) → tert-butyl (3R)-3-(4-fluoro-1H-pyrazol-1-yl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20 - 50℃; Inert atmosphere;	84%
With caesium carbonate In N,N-dimethyl-formamide at 20 - 50℃;	84%

3-acetyl-6-chloropyridine (55676-22-7) + 4-fluoro-1H-pyrazole (35277-02-2) → 1-(6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl)ethane-1-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 16h;	83%

2-chlorpropionitrile (1617-17-0) + 4-fluoro-1H-pyrazole (35277-02-2) → 2-(4-fluoro-1H-pyrazol-1-yl)propanenitrile

Conditions	Yield
With caesium carbonate In acetonitrile at 100℃; for 2h;	82%

4-fluoro-1H-pyrazole (35277-02-2) + 5-chloro-2-pyrazinecarbonitrile (36070-75-4) → 5-(4-fluoro-1H-pyrazol-1-yl)pyrazine-2-carbonitrile

Conditions	Yield
With potassium acetate In N,N-dimethyl-formamide at 100℃; for 4h;	82%
With potassium acetate In N,N-dimethyl-formamide at 100℃; for 4h;	82%
With potassium acetate In N,N-dimethyl-formamide at 100℃; for 4h;	82%
With potassium acetate In N,N-dimethyl-formamide at 100℃; for 4h;	82%
With potassium acetate In N,N-dimethyl-formamide at 100℃; for 4h;	82%

CYANAMID (420-04-2) + 4-fluoro-1H-pyrazole (35277-02-2) → 4-fluoro-1H-pyrazole-1-carboxamidine hydrochloride (1428527-45-0)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane for 2h; Reflux; Inert atmosphere;	80%
With hydrogenchloride In 1,4-dioxane for 2h; Reflux; Inert atmosphere;	80%

3-(3-(4-(chloromethyl)benzyl)isoxazol-5-yl)pyridin-2-amine + 4-fluoro-1H-pyrazole (35277-02-2) → 3-(3-(4-((4-fluoro-1H-pyrazol-1-yl)methyl)benzyl)isoxazol-5-yl)pyridin-2-amine

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 60℃; for 0.0833333h;	80%
With potassium tert-butylate In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 60℃; for 0.0833333h;	80%

2-bromo-1-[4-(trifluoromethoxy)phenyl]propan-1-one + 4-fluoro-1H-pyrazole (35277-02-2) → 2-(4-fluoro-1H-pyrazol-1-yl)-1-[4-(trifluoromethoxy)phenyl]propan-1-one

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃;	79%

4-fluoro-1H-pyrazole (35277-02-2) + cyanomethyl bromide (590-17-0) → 2-(4-fluoro-1H-pyrazol-1-yl)acetonitrile

Conditions	Yield
With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 12.6667h;	76%
With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 12.6667h;	1 g

(S)-N-(3-chloro-4-cyanophenyl)-2-methyloxirane-2-carboxamide (1010729-04-0) + 4-fluoro-1H-pyrazole (35277-02-2) → (S)-N-(3-chloro-4-cyanophenyl)-3-(4-fluoro-1H-pyrazol-1-yl)-2-hydroxy-2-methylpropanamide

Conditions	Yield
Stage #1: 4-fluoro-1H-pyrazole With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: (S)-N-(3-chloro-4-cyanophenyl)-2-methyloxirane-2-carboxamide In tetrahydrofuran; mineral oil at 20℃; Inert atmosphere; Cooling with ice;	72%
Stage #1: 4-fluoro-1H-pyrazole With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 3h; Inert atmosphere; Stage #2: (S)-N-(3-chloro-4-cyanophenyl)-2-methyloxirane-2-carboxamide In tetrahydrofuran; mineral oil at 20℃; Inert atmosphere;

4-fluoro-1H-pyrazole (35277-02-2) + (S)-(-)-3-bromo-2-hydroxy-2-methyl-N-[(4-cyano-3-(trifluoromethyl)phenyl)]propanamide (113181-02-5) → (R)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-fluoro-1H-pyrazol-1-yl)-2-hydroxy-2-methylpropanamide

Conditions	Yield
Stage #1: 4-fluoro-1H-pyrazole With sodium hydride In tetrahydrofuran; mineral oil for 3h; Cooling with ice; Inert atmosphere; Stage #2: (S)-(-)-3-bromo-2-hydroxy-2-methyl-N-[(4-cyano-3-(trifluoromethyl)phenyl)]propanamide In tetrahydrofuran; mineral oil at 20℃; Inert atmosphere;	71%
Stage #1: 4-fluoro-1H-pyrazole With sodium hydride In tetrahydrofuran; mineral oil for 3h; Inert atmosphere; Cooling with ice; Stage #2: (S)-(-)-3-bromo-2-hydroxy-2-methyl-N-[(4-cyano-3-(trifluoromethyl)phenyl)]propanamide In tetrahydrofuran; mineral oil at 20℃; Inert atmosphere;	64%
Stage #1: 4-fluoro-1H-pyrazole With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 3h; Inert atmosphere; Stage #2: (S)-(-)-3-bromo-2-hydroxy-2-methyl-N-[(4-cyano-3-(trifluoromethyl)phenyl)]propanamide In tetrahydrofuran; mineral oil at 20℃; Inert atmosphere;	64%

N-((S)-2-cyano-1-(4-(ethylsulfonyl)phenyl)ethyl)-4-((2S,4S)-2-((difluoromethoxy)methyl)-4-(4-iodophenoxy)pyrrolidin-1-yl)benzamide + 4-fluoro-1H-pyrazole (35277-02-2) → N-((S)-2-cyano-1-(4-(ethylsulfonyl)phenyl)ethyl)-4-((2S,4S)-2-((difluoromethoxy)methyl)-4-(4-(4-fluoro-1H-pyrazol-1-yl)phenoxy)pyrrolidin-1-yl)benzamide

Conditions	Yield
With copper(l) iodide; potassium carbonate; methyl (S)-2-methylpyrrolidine-2-carboxylate monohydrochloride In dimethyl sulfoxide at 100℃; for 16h; Inert atmosphere;	71%

1-methyl-2(1H)-quinoxalinone (6479-18-1) + 4-fluoro-1H-pyrazole (35277-02-2) → 3-(4-fluoro-1H-pyrazol-1-yl)-1-methylquinoxalin-2(1H)-one

Conditions	Yield
With tetrabutylammonium tetrafluoroborate In acetonitrile at 20℃; for 8h; Electrolysis;	70%

C29H36O4SSi + 4-fluoro-1H-pyrazole (35277-02-2) → C25H31FN2OSi

Conditions	Yield
Stage #1: 4-fluoro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.333333h; Stage #2: C29H36O4SSi In N,N-dimethyl-formamide at 100℃; for 4h;	68%

4-fluoro-1H-pyrazole (35277-02-2) + 4-Fluoronitrobenzene (350-46-9) → 4-fluoro-1-(4'-nitrophenyl)pyrazole (35250-01-2)

Conditions	Yield
With potassium carbonate In acetonitrile at 70℃; for 2h;	67%

4-fluoro-1H-pyrazole (35277-02-2) + N-[4-nitro-3-(trifluoromethyl)phenyl]-(2R)-3-bromo-2-hydroxy-2-methylpropanamide (206193-18-2) → (S)-3-(4-fluoro-1H-pyrazol-1-yl)-2-hydroxy-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide

Conditions	Yield
Stage #1: 4-fluoro-1H-pyrazole With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Cooling with ice; Stage #2: N-[4-nitro-3-(trifluoromethyl)phenyl]-(2R)-3-bromo-2-hydroxy-2-methylpropanamide In tetrahydrofuran; mineral oil at 20℃; Inert atmosphere; Cooling with ice;	67%
Stage #1: 4-fluoro-1H-pyrazole With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Stage #2: N-[4-nitro-3-(trifluoromethyl)phenyl]-(2R)-3-bromo-2-hydroxy-2-methylpropanamide In tetrahydrofuran; mineral oil at 20℃; Inert atmosphere;	67%

4-fluoro-1H-pyrazole (35277-02-2) + 2-bromoethanol (540-51-2) → 2-(4-fluoropyrazol-1-yl)ethanol (1207961-59-8)

Conditions	Yield
Stage #1: 4-fluoro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Stage #2: 2-bromoethanol In N,N-dimethyl-formamide; mineral oil at 0 - 40℃;	66%
Stage #1: 4-fluoro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 0 - 23℃; Stage #2: 2-bromoethanol In N,N-dimethyl-formamide at 0 - 40℃;	66%

Upstream product

• 102-52-3 malonaldehydebis(dimethylacetal) 
• 761-88-6 (Z)-3-(dimethylamino)-2-fluoroacrylaldehyde 
• 761-88-6 β-(Dimethylamino)-α-fluoropropenal 
• 139680-79-8 β-(Diethylamino)-α-fluoropropenal 
• 38346-22-4 fluoro(trimethylsilyl)acetylene 
• 853180-40-2 4-fluoro-5-(tributylstannyl)-1H-pyrazole 
• 186581-53-3 diazomethane 
• 75-38-7 Vinylidene fluoride 
• 128229-03-8 (Z)-(2,3,3-trifluoro-l-propenyl)trimethylammonium iodide 
• 109-89-7 diethylamine 
• 64-17-5 ethanol 
• 40623-35-6 7-chloro-7-fluoro-2,5-dioxabicyclo<4.1.0>heptane 

Downstream Products

• 701213-60-7 1-(4-benzoylpiperazin-1-yl)-2-(7-(4-fluoro-1H-pyrazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione 
• 1207961-59-8 2-(4-fluoropyrazol-1-yl)ethanol 
• 1231747-27-5 C₁₀H₇F₂IN₂ 

Relevant articles and documents

Synthesis and reactions of 5-tributylstannyl-4-fluoro-1H-pyrazole

The palladium-catalyzed cross-coupling reactions of 5-tributylstannyl-4-fluoro-1H-pyrazole with aryl iodides provided high yields of the corresponding 5-aryl-4-fluoro-1H-pyrazoles. Furthermore, these cross-coupling reactions proceeded smoothly under an atmosphere of carbon monoxide (CO) to afford the corresponding 5-acyl-4-fluoro-1H-pyrazoles as CO-insertion products.

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