4640-67-9

Basic information

• Product Name: 4-FLUOROBENZOYLACETONITRILE
• Synonyms: P-FLUOROBENZOYLACETONITRILE;AKOS B020924;3-(4-FLUORO-PHENYL)-3-OXO-PROPIONITRILE;3-(4'-FLUOROPHENYL)-3-OXOPROPANENITRILE;3-(4-FLUOROPHENYL)-3-OXOPROPANENITRILE;4-FLUOROBENZOYLACETONITRILE;ART-CHEM-BB B020924;BUTTPARK 34\07-91
• CAS NO: 4640-67-9
• Molecular Formula: C₉H₆FNO
• Molecular Weight: 163.15
• EINECS: 1308068-626-2
• Product Categories: HALIDE
• Mol File: 4640-67-9.mol
• Article Data: 42

Chemical Properties

• Melting Point: 84-88 °C
• Boiling Point: 311.9 °C at 760 mmHg
• Flash Point: 142.4 °C
• Appearance: Yellow/Solid
• Density: 1.207 g/cm³
• Vapor Pressure: 0.000547mmHg at 25°C
• Refractive Index: 1.516
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Soluble in dimethylformamide, dimethyl sulfoxide.
• PKA: 7.67±0.10(Predicted)
• CAS DataBase Reference: 4-FLUOROBENZOYLACETONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-FLUOROBENZOYLACETONITRILE(4640-67-9)
• EPA Substance Registry System: 4-FLUOROBENZOYLACETONITRILE(4640-67-9)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-22
• Safety Statements: 26-36/37/39
• WGK Germany: 3
• HazardClass: 6.1
• Hazardous Substances Data: 4640-67-9(Hazardous Substances Data)

Usage

Chemical Properties

White to light brown solid

Uses

4-Fluorobenzoylacetonitrile is used as a reagent in the synthesis of Blonanserin (B595850); a 5-HT2 serotonin receptor and D2 dopamine receptor antagonist, used as an antipsychotic. 4-Fluorobenzoylacetonitrile is also used in the preparation of pyrazolopyrimidines as potential antimicrobial and antioxidant agents.

InChI:InChI=1/C9H6FNO/c10-8-3-1-7(2-4-8)9(12)5-6-11/h1-4H,5H2

Synthetic route

1-(4-fluorophenyl)-2-methoxyethan-1-one (247179-37-9) + acetonitrile (75-05-8) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
Stage #1: 1-(4-fluorophenyl)-2-methoxyethan-1-one With sodium hydride In toluene at 90℃; for 2h; Stage #2: acetonitrile In toluene for 6.5h;	93.14%

4-fluoro-N-methoxy-N-methylbenzamide (116332-54-8) + acetonitrile (75-05-8) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
Stage #1: acetonitrile With methyllithium; lithium bromide In tetrahydrofuran; diethyl ether at -78℃; for 0.5h; Inert atmosphere; Stage #2: 4-fluoro-N-methoxy-N-methylbenzamide In tetrahydrofuran; diethyl ether at -78℃; for 1.5h; Inert atmosphere;	93%

fluorobenzene (462-06-6) + malononitrile (109-77-3) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With trifluorormethanesulfonic acid In chloroform at 20 - 80℃; for 12.5h;	92.39%

sodium cyanide (143-33-9) + 2-bromo-4'-fluoroacetophenone (403-29-2) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
	89%

α-(tert-butylcarboxy)-β-hydroxy-p-fluorocinnamonitrile (133550-56-8) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With trifluoroacetic acid In dichloromethane for 3.5h; Ambient temperature;	83%

methyl 4-flurobenzoate (403-33-8) + acetonitrile (75-05-8) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With sodium hexamethyldisilazane In tetrahydrofuran; toluene at -5 - 0℃; Reagent/catalyst; Solvent; Temperature; Large scale;	83%
With sodium hydride In toluene Reflux;	78%
With sodium hydride In tetrahydrofuran for 5h; Reflux; Inert atmosphere;

4-fluorobenzoyl chloride (403-43-0) + cyanoacetic acid (372-09-8) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
Stage #1: cyanoacetic acid With [2,2]bipyridinyl; n-butyllithium; magnesium sulfate In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 4-fluorobenzoyl chloride In tetrahydrofuran; methanol; hexane at -78 - 20℃; Inert atmosphere; Stage #3: With hydrogenchloride In tetrahydrofuran; methanol; hexane; water	80%

sodium cyanide (773837-37-9) + 2-bromo-4'-fluoroacetophenone (403-29-2) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With tetrabutylammomium bromide In water; toluene at 20℃; chemoselective reaction;	80%
In ethanol; water for 16h; Cooling with ice;

diazoacetonitrile (13138-21-1) + 4-fluorobenzaldehyde (459-57-4) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With boron trifluoride diethyl etherate In dichloromethane at 20℃;	77%

4-fluoroboronic acid (1765-93-1) + malononitrile (109-77-3) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With 4,4'-dimethyl-2,2'-bipyridines; palladium(II) acetylacetonate; toluene-4-sulfonic acid In water; toluene at 80℃; for 24h; Schlenk technique;	76%
With 4,4'-dimethyl-2,2'-bipyridines; water; palladium(II) acetylacetonate; benzenesulfonic acid In toluene at 80℃; for 28h;	76%

cyanoacetic acid tert-butyl ester (1116-98-9) + 9-methyl-9H-fluorene-9-carbonyl chloride (82102-37-2) + 1-Bromo-4-fluorobenzene (460-00-4) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions

Yield

Stage #1: cyanoacetic acid tert-butyl ester; 9-methyl-9H-fluorene-9-carbonyl chloride; 1-Bromo-4-fluorobenzene With dichloro(1,5-cyclooctadiene)palladium(II); N-Methyldicyclohexylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; magnesium chloride; tri tert-butylphosphoniumtetrafluoroborate In 1,4-dioxane at 100℃; for 18h; Glovebox; Inert atmosphere; Stage #2: With formic acid In 1,4-dioxane for 1h; Inert atmosphere;

74%

3-chloro-3-(4-fluorophenyl)acrylonitrile (205984-77-6) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With sodium hydroxide In water; dimethyl sulfoxide at 25℃;	71%

trimethylsilyl cyanide (7677-24-9) + ((1-(4-fluorophenyl)vinyl)oxy)trimethylsilane (58518-77-7) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With iodosylbenzene; boron trifluoride diethyl etherate In acetonitrile at -30℃; for 3h; Inert atmosphere;	68%

2-trimethylsilylacetonitrile (18293-53-3) + 4-fluoro-1-iodobenzene (352-34-1) + carbon monoxide (201230-82-2) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With zinc(II) fluoride; (2-methylallyl)palladium-chloride dimer; copper(ll) bromide In N,N-dimethyl-formamide at 80℃; under 7600.51 Torr; for 12h;	65%

methyl 4-flurobenzoate (403-33-8) + acetonitrile (75-05-8) → 4-Fluorobenzoic acid (456-22-4) + 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With sodium hydride In tert-butyl methyl ether; water at 90℃;	A 17.5% B 64%

2-trimethylsilylacetonitrile (18293-53-3) + 4-fluoro-1-iodobenzene (352-34-1) + molybdenum hexacarbonyl (13939-06-5, 199620-15-0) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With copper (II)-fluoride; bis-triphenylphosphine-palladium(II) chloride In acetonitrile at 80℃; for 16h;	61%

sodium cyanide (143-33-9) + 2-Chloro-4'-fluoroacetophenone (456-04-2) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
	56%

4-fluorobenzoic acid ethyl ester (451-46-7) + acetonitrile (75-05-8) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
Stage #1: acetonitrile With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 4-fluorobenzoic acid ethyl ester In tetrahydrofuran; hexane at -78 - -60℃; for 3h;	47%
With sodium hydride In benzene for 14h; Heating;	31%
With potassium 2-methylbutan-2-olate In tetrahydrofuran; toluene at 20℃; for 0.333333h; Inert atmosphere;
With sodium hydride In tetrahydrofuran for 1h; Reflux;
With sodium hydride In toluene for 2h;

potassium cyanide (151-50-8) + 2-bromo-4'-fluoroacetophenone (403-29-2) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
Stage #1: potassium cyanide; 2-bromo-4'-fluoroacetophenone In ethanol; water at 20℃; for 2h; Stage #2: With hydrogenchloride In ethanol; water pH=5 - 6;	6%
In ethanol; water at 20℃; for 2h; Substitution;

(E/Z)-3-amino-3-(4-fluorophenyl)acrylonitrile (55330-46-6) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With hydrogenchloride In chloroform
With hydrogenchloride In water at 20℃; for 3h;	91.9 g

sodium cyanide (143-33-9) + 2-chloro-1-(4-fluoro-phenyl)-3-phenyl-propane-1,3-dione → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + 2-benzoyl-3-hydroxy-3-phenylacrylonitrile + (Z)-2-Benzoyl-3-(4-fluoro-phenyl)-3-hydroxy-acrylonitrile + (Z)-2-(4-Fluoro-benzoyl)-3-(4-fluoro-phenyl)-3-hydroxy-acrylonitrile

Conditions	Yield
In dimethyl sulfoxide at 20℃; for 3h; Further byproducts given. Title compound not separated from byproducts;

1-(4'-fluorophenyl)-3-phenylpropane-1,3-dione (38448-95-2) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent / NCS / CCl4 / 0.5 h / Heating 2: dimethylsulfoxide / 3 h / 20 °C View Scheme

fluorobenzene (462-06-6) + benzothienyllithium → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 73 percent / AlCl3 / CS2 2: 56 percent View Scheme

4-fluorobenzoyl chloride (403-43-0) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) ether, 20 min, 2.) ether, RT, 3 h 2: 83 percent / TFA / CH2Cl2 / 3.5 h / Ambient temperature View Scheme

4-fluorobenzonitrile (1194-02-1) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaH, tBuOH / diethyl ether / Heating 2: aq. HCl / CHCl3 View Scheme

acetonitrile (75-05-8) + p-fluoro-benzoic acid ester → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With potassium 2-methylbutan-2-olate In tetrahydrofuran; toluene at 20℃;

4-fluorobenzylic alcohol (459-56-3) + acetonitrile (75-05-8) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With oxygen; potassium hydroxide; copper dichloride In N,N-dimethyl acetamide at 20℃; for 12h; Green chemistry;

1-(4-fluorophenyl)ethanone (403-42-9) → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium iodide; triethylamine / acetonitrile / 40 °C / Inert atmosphere 2: boron trifluoride diethyl etherate; iodosylbenzene / acetonitrile / 3 h / -30 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: copper(ll) bromide / ethyl acetate / Reflux 2: ethanol; water / 16 h / Cooling with ice View Scheme

C11H8FNO3 → 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9)

Conditions	Yield
With water; lithium iodide In 1-methyl-pyrrolidin-2-one at 130℃; for 6h; Krapcho Dealkoxycarbonylation;

cycloactanone (502-49-8) + 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) → 4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocyclooctane[b]pyridine-(1H)-ketone (132812-72-7)

Conditions	Yield
With 1-ethyl-3-methylimidazolium tetrafluoroborate at 120℃; for 1h;	99.8%
With methanesulfonic acid; phosphorus pentoxide at 50℃; for 15h;	95%
With PPA Heating;	64%
With phosphoric acid; toluene-4-sulfonic acid In toluene Reflux; Dean-Stark; Large scale;	54%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + cyclopentanone (120-92-3) → (2-amino-5,6-dihydro-4H-cyclopenta[b]thiophen-3-yl)-(4-fluoro-phenyl)-methanone (304018-03-9)

Conditions	Yield
With morpholine; sulfur In ethanol at 60℃; for 2h;	98%
With sulfur In ethanol at 50℃; for 4h;	74%
With morpholine; sulfur In ethanol at 70℃; for 1h; Cyclization;	45%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + (E)-1,1,1-trifluoro-4-phenyl-3-buten-2-one (3108-32-5, 86571-25-7) → 2-(4-fluorophenyl)-6-hydroxy-4-phenyl-6-(trifluoromethyl)-5,6-dihydro-4H-pyran-3-carbonitrile (1204589-64-9)

Conditions	Yield
Stage #1: 3-(4-fluorophenyl)-3-oxopropionitrile With (S)-1-(1-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenylpropan-2-yl)-3-(3,5-bis(trifluoromethyl)phenyl)thiourea In chloroform at -10℃; Michael addition; Stage #2: (E)-1,1,1-trifluoro-4-phenyl-3-buten-2-one In chloroform at -10℃; Michael addition; optical yield given as %ee; enantioselective reaction;	98%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + 5-amino-1-phenyl-3-(pyridin-3-yl)-1H-pyrazole (1152711-48-2) + 4-methoxy-benzaldehyde (123-11-5) → 6-(4-fluorophenyl)-4-(4-methoxyphenyl)-1-phenyl-3-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (1357585-60-4)

Conditions	Yield
With acetic acid; triethylamine at 150℃; for 0.25h; Microwave irradiation;	98%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + 4-dimethylamino-benzaldehyde (100-10-7) → (E)-3-(4-(dimethylamino)phenyl)-2-(4-fluorobenzoyl)acrylonitrile (1370042-90-2)

Conditions	Yield
With piperidine In (+/-)-2-pentanol at 120℃; for 0.25h; Knoevenagel condensation; Microwave irradiation;	98%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) → (RS)-3-(4-fluorophenyl)-3-hydroxypropionitrile (136568-65-5)

Conditions	Yield
With formic acid; C18H24ClIrN3 In water at 80℃; for 3h; Schlenk technique; Inert atmosphere; chemoselective reaction;	97%
With formic acid; 4-methoxy-N-(1-(naphthalen-2-yl)ethylidene)aniline; sodium formate In water at 80℃; for 18h; pH=4.5; Inert atmosphere; chemoselective reaction;	91%
With sodium tetrahydroborate In ethanol at 0 - 20℃;	82%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) → 3-(4-fluorophenyl)-3-oxopropanamide

Conditions	Yield
With dihydrogen peroxide; tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide In dichloromethane at 20℃; Reagent/catalyst; Cooling with ice;	97%
With sulfuric acid In water at 20℃;
With methanesulfonic acid In water at 65 - 70℃; for 3h;

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + C15H16O4 → C22H18FNO3

Conditions	Yield
Stage #1: 3-(4-fluorophenyl)-3-oxopropionitrile With C33H28F5N3O2; potassium carbonate In toluene at 0℃; for 0.0833333h; Stage #2: C15H16O4 In toluene at 0℃; for 48h; enantioselective reaction;	97%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + C15H16O4 → C22H18FNO3

Conditions	Yield
With C33H28F5N3O2; potassium carbonate In toluene at 0℃; for 48h; enantioselective reaction;	97%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) → 3-(4-fluorophenyl)-1H-pyrazol-5-amine (72411-52-0, 1242422-48-5)

Conditions	Yield
With hydrazine hydrate In methanol at 150℃; for 0.0833333h; Microwave irradiation;	96%
With hydrazine hydrate In ethanol at 80℃; for 4h;	33%
With hydrazine In ethanol for 12h; Reflux;

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + methyl benzylidenepyruvate (107969-78-8) → methyl 5-cyano-6-(4-fluorophenyl)-2-hydroxy-4-phenyl-3,4-dihydro-2H-pyran-2-carboxylate (1435943-40-0)

Conditions	Yield
With C36H50N4O4; 4-(1,1-dimethylethyl)benzoic acid In tert-butyl methyl ether at -30℃; for 72h; Michael Addition; Molecular sieve; Inert atmosphere;	96%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + 2-amino-benzenethiol (137-07-5) → 2-(4-fluorophenyl)-benzothiazole (1629-26-1)

Conditions	Yield
at 200℃; for 0.166667h; Irradiation; microwave;	95%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) → (R)-3-(4'-fluorophenyl)-3-hydroxypropanenitrile

Conditions	Yield
With formic acid; {Cp*Ir[(R,R)-C6F5SO2DPEN](H2O)}(SO4) In water at 20℃; for 24h; pH=3.5; optical yield given as %ee; enantioselective reaction;	95%
With D-glucose; D-glucose dehydrogenase; NADPH; Candida magnoliae carbonyl reductase In phosphate buffer; dimethyl sulfoxide at 20℃; for 24h; pH=7.0;	90%
With formic acid In water at 25℃; for 12h; pH=3.5; enantioselective reaction;	n/a

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + p-toluidine (106-49-0) → 3-(4-fluorophenyl)-3-(p-tolylamino)acrylonitrile (1159001-65-6)

Conditions	Yield
With acetic acid at 80℃; for 6h; optical yield given as %de;	95%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + methyl benzylidenepyruvate (107969-78-8) → (2S,4R)-methyl-5-cyano-6-(4-fluorophenyl)-2-hydroxy-4-phenyl-3,4-dihydro-2H-pyran-2-carboxylate (1217974-60-1)

Conditions	Yield
With (S)-1-(1-(4-(benzyloxy)phenyl)-3-(dimethylamino)propan-2-yl)-3-(3,5-bis(trifluoromethyl)phenyl)thiourea In diethyl ether at 20℃; for 12h; Michael addition; optical yield given as %ee; enantioselective reaction;	95%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + cis-(±)-4-[(methoxycarbonyl)oxy]cyclohex-2-en-1-yl methyl carbonate → (3aS,7aS)-2-(4-fluorophenyl)-3a,4,5,7a-tetrahydrobenzofuran-3-carbonitrile

Conditions	Yield
With bis(η3-allyl-μ-chloropalladium(II)); C48H50N2O2P2Ru In 1,4-dioxane at 20℃; for 24h; Schlenk technique; Inert atmosphere; stereoselective reaction;	95%

2-amino-5-chlorobenzenethiol (23474-98-8) + 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) → 6-chloro-2-(4-fluorophenyl)benzo[d]thiazole

Conditions	Yield
at 200℃; for 0.166667h; Irradiation; microwave;	94%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + 5-chloroindole 2,3-dione (17630-76-1) + malononitrile (109-77-3) → 2'-amino-5-chloro-6'-(4-fluorophenyl)-2-oxospiro[indoline-3,4'-pyran]-3',5'-dicarbonitrile

Conditions	Yield
In ethanol; water at 20℃; Irradiation; Green chemistry;	94%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + Cysteamine (60-23-1) → 2-(4-fluorophenyl)-4,5-dihydrothiazole (96159-82-9)

Conditions	Yield
at 210℃; under 7757.43 Torr; for 0.166667h; microwave irradiation;	93%

2-(dimethyl(oxo)-λ6-sulfaneylidene)-1-phenylethan-1-one (20718-17-6) + 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) → (±)-5-fluoro-2-hydroxy-2,8-diphenyl-2,3-dihydrobenzo[de]chromene-9-carbonitrile

Conditions	Yield
With Cp*Rh(OAc)2·H2O; water In 1,2-dichloro-ethane at 80℃; for 12h; Schlenk technique; Inert atmosphere;	93%

5-nitroisatin (611-09-6) + 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + malononitrile (109-77-3) → 2'-amino-6'-(4-fluorophenyl)-5-nitro-2-oxospiro[indoline-3,4'-pyran]-3',5'-dicarbonitrile

Conditions	Yield
In ethanol; water at 20℃; Irradiation; Green chemistry;	93%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + 1-p-toluenesulfonyl-4-ethynyl-1,4-dihydro-2H-benzo[d][1,3]-azahexan-2-one → N-(2-(4-cyano-5-(4-fluorophenyl)-2-methylfuran-3-yl)phenyl)-4-methylbenzenesulfonamide

Conditions	Yield
With copper acetylacetonate; o-phenylenebis(diphenylphosphine); N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 24h; Inert atmosphere;	93%

ethanol (64-17-5) + 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) → 3-(4-Fluorphenyl)-3-oxo-propionimidsaeure-ethylester-hydrochlorid (81471-35-4)

Conditions	Yield
With hydrogenchloride In diethyl ether; chloroform; benzene Ambient temperature;	92%

methanol (67-56-1) + 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) → methyl (p-fluorobenzoyl)formate (156276-23-2)

Conditions	Yield
With oxygen In tetrahydrofuran at 20℃; for 24h; Irradiation;	92%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + benzaldehyde (100-52-7) + malononitrile (109-77-3) → 2-amino-6-(4-fluorophenyl)-4-phenyl-4H-pyran-3,5-dicarbonitrile

Conditions	Yield
In ethanol; water at 20℃; Irradiation; Green chemistry;	92%

3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + indole-2,3-dione (91-56-5) + malononitrile (109-77-3) → 2'-amino-6'-(4-fluorophenyl)-2-oxospiro[indoline-3,4'-pyran]-3',5'-dicarbonitrile

Conditions	Yield
In ethanol; water at 20℃; Irradiation; Green chemistry;	92%

5-fluoro-1H-indole-2,3-dione (443-69-6) + 3-(4-fluorophenyl)-3-oxopropionitrile (4640-67-9) + malononitrile (109-77-3) → 2'-amino-5-fluoro-6'-(4-fluorophenyl)-2-oxospiro[indoline-3,4'-pyran]-3',5'-dicarbonitrile

Conditions	Yield
In ethanol; water at 20℃; Irradiation; Green chemistry;	92%

Upstream product

• 143-33-9 sodium cyanide 
• 456-04-2 2-Chloro-4'-fluoroacetophenone 
• 451-46-7 4-fluorobenzoic acid ethyl ester 
• 75-05-8 acetonitrile 
• 459-56-3 4-fluorobenzylic alcohol 
• 247179-37-9 1-(4-fluorophenyl)-2-methoxyethan-1-one 
• 403-33-8 methyl 4-flurobenzoate 
• 133550-56-8 α-(tert-butylcarboxy)-β-hydroxy-p-fluorocinnamonitrile 
• 459-57-4 4-fluorobenzaldehyde 
• 205984-77-6 3-chloro-3-(4-fluorophenyl)acrylonitrile 
• 13656-36-5 3,5-dichloro-2,4,6-trifluorobenzoic acid 
• 1765-93-1 4-fluoroboronic acid 
• 109-77-3 malononitrile 
• 316142-60-6 N-(4-cyanophenyl)-4-fluorobenzamide 

Downstream Products

• 81471-35-4 3-(4-Fluorphenyl)-3-oxo-propionimidsaeure-ethylester-hydrochlorid 
• 870678-48-1 (2E)-3-amino-3-[(4-chlorophenyl)thio]-1-(4-fluorophenyl)prop-2-en-1-one 
• 618092-86-7 5-amino-3-(4-fluorophenyl)-1-(p-tolyl)-1H-pyrazole 
• 96159-82-9 2-(4-fluorophenyl)-4,5-dihydrothiazole 
• 237435-44-8 ethyl 3-amino-5-(4-fluorophenyl)pyrrole-2-carboxylate 
• 237435-46-0 4-chloro-6-(4-fluorophenyl)-2-methylpyrrolo[3,2-d]pyrimidine 
• 237435-45-9 6-(4-fluorophenyl)-2-methylpyrrolo[3,2-d]pyrimidine-4-ol 
• 81471-48-9 2-Amino-6-phenyl-pyrid-3-yl-(4-fluorphenyl)-keton 
• 602309-31-9 4-chlorophenyl 3-(4-fluorophenyl)-3-oxopropanimidothioate hydrochloride 
• 1154198-60-3 1-(4,6-dimethylpyrimidin-2-yl)-5-amino-3-(4-fluorophenyl)pyrazole 
• 1455243-24-9 1-(4,6-dimethylpyrimidin-2-yl)-5-(N-acetamide)-3-(4-fluorophenyl)pyrazole 
• 1455243-38-5 1-(4,6-dimethylpyrimidin-2-yl)-5-(2,2,2-trifluoro-N-acetamide)-3-(4-fluorophenyl)pyrazole 
• 1813-94-1 ethyl 4-fluorobenzoylformate 

Relevant articles and documents

One-pot three-component synthesis of novel pyrazolo[3,4-b]pyridines as potent antileukemic agents

In the current study, we report on the development of novel series of pyrazolo[3,4-b]pyridine derivatives (8a-u, 11a-n, and 14a,b) as potential anticancer agents. The prepared pyrazolo[3,4-b]pyridines have been screened for their antitumor activity in vitro at NCI-DTP. Thereafter, compound 8a was qualified by NCI for full panel five-dose assay to assess its GI50, TGI and LC50 values. Compound 8a showed broad-spectrum anti-proliferative activities over the whole NCI panel, with outstanding growth inhibition full panel GI50 (MG-MID) value equals 2.16 μM and subpanel GI50 (MG-MID) range: 1.92–2.86 μM. Furthermore, pyrazolo[3,4-b]pyridines 8a, 8e-h, 8o, 8u, 11a, 11e, 11h, 11l and 14a-b were assayed for their antiproliferative effect against a panel of leukemia cell lines (K562, MV4-11, CEM, RS4;11, ML-2 and KOPN-8) where they possessed moderate to excellent anti-leukemic activity. Moreover, pyrazolo[3,4-b]pyridines 8o, 8u, 14a and 14b were further explored for their effect on cell cycle on RS4;11 cells, in which they dose-dependently increased populations of cells in G2/M phases. Finally we analyzed the changes of selected proteins (HOXA9, MEIS1, PARP, BcL-2 and McL-1) related to cell death and viability in RS4;11 cells via Western blotting. Collectively, the obtained results suggested pyrazolo[3,4-b]pyridines 8o, 8u, 14a and 14b as promising lead molecules for further optimization to develop more potent and efficient anticancer candidates.

Method for synthesizing beta-ketonitrile and derivatives thereof

The invention discloses a method for synthesizing beta-ketonitrile and derivatives thereof. The beta-ketonitrile is prepared by a reaction of malononitrile and derivatives thereof with arylboronic acid. According to the invention, reactants are wide in source and low in cost; the reaction is carried out in a solvent, and the solvent is a mixture of toluene and water; in the process of the reaction, a palladium catalyst, an acid additive and a ligand are also added into the solvent; the acidic additive is any one selected from benzenesulfonic acid, p-toluenesulfonic acid, p-nitrobenzenesulfonic acid, trifluoromethanesulfonic acid and trifluoroformic acid; and the ligand is any one selected from 4,4'-dimethyl-2,2'-bipyridyl, 6,6'-dimethyl-2,2'-bipyridyl and 5,5'-dimethyl-2,2'-bipyridyl. The method in the invention can directly synthesize the target product in one step, does not need to separate an intermediate product, can obtain the target product only by a stirring reaction under normal pressure, has the highest yield of 98%, is especially suitable for synthesis of beta-ketonitrile derivatives sensitive to alkaline conditions, and provides better guarantee for development of organic compounds related to beta-ketonitrile derivatives.

Deadly KCN and pricey metal free track for accessing β-ketonitriles employing mild reaction conditions

A one pot synthesis of β-ketonitriles from readily accessible 3-chloropropenals using economically benign iodine, aqueous ammonia and sodium hydroxide solution, employing mild reaction conditions have been described. This report presents a convenient, inexpensive, highly toxic-matter-free and eco-friendly approach for β-ketonitriles.