N-(4-fluorophenyl)-N-(4-hydroxyphenyl)cyclopropane-1,1-dicarboxamide

N-(4-fluorophenyl)-N-(4-hydroxyphenyl)cyclopropane-1,1-dicarboxamide Property

Boiling point:

639.7±50.0 °C(Predicted)

Density 

1.486±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

10.11±0.26(Predicted)

Appearance

Off-white to light brown Solid

InChI

InChI=1S/C17H15FN2O3/c18-11-1-3-12(4-2-11)19-15(22)17(9-10-17)16(23)20-13-5-7-14(21)8-6-13/h1-8,21H,9-10H2,(H,19,22)(H,20,23)

InChIKey

FSFMBVMXIPQPMJ-UHFFFAOYSA-N

SMILES

C1(C(NC2=CC=C(O)C=C2)=O)(C(NC2=CC=C(F)C=C2)=O)CC1

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H226Flammable liquid and vapour

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P210Keep away from heat/sparks/open flames/hot surfaces. — No smoking.

P233Keep container tightly closed.

P240Ground/bond container and receiving equipment.

P241Use explosion-proof electrical/ventilating/lighting/…/equipment.

P242Use only non-sparking tools.

P243Take precautionary measures against static discharge.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P303+P361+P353IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P370+P378In case of fire: Use … for extinction.

P403+P235Store in a well-ventilated place. Keep cool.

P501Dispose of contents/container to..…

N-(4-fluorophenyl)-N-(4-hydroxyphenyl)cyclopropane-1,1-dicarboxamide Chemical Properties,Usage,Production

Uses

N-(4-Fluorophenyl)-N''-(4-hydroxyphenyl)-1,1-cyclopropanedicarboxamide can be used to treat kinase-dependenet disorders.

Synthesis

GENERAL STEPS: To a solution of 4-aminophenol (2.93 g, 26.9 mmol) and 1-(4-fluorophenylcarbamoyl)cyclopropanecarboxylic acid (5.00 g, 22.4 mmol) in N,N-dimethylacetamide (DMA, 30 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 5.15 g, 26.9 mmol). The reaction mixture was stirred vigorously at room temperature until the reaction was complete (monitored by TLC, about 3 hours). Upon completion of the reaction, the reaction mixture was slowly poured into a flask containing saturated sodium bicarbonate (NaHCO3, 200 mL) aqueous solution under vigorous stirring. After continued stirring for 1 h, the resulting suspension was filtered. The solid product was collected, washed sequentially with water (50 mL) and chloroform (50 mL), and then dried under vacuum to afford N-(4-fluorophenyl)-N-(4-hydroxyphenyl)cyclopropane-1,1-dicarboxamide (6.22 g, 88% yield) as a white powder (HPLC purity >95%, and structure confirmed by 1H NMR).

References

[1] Patent: WO2005/30140, 2005, A2. Location in patent: Page/Page column 205
[2] Patent: CN106632028, 2017, A. Location in patent: Paragraph 0079; 0084; 0085
[3] Patent: WO2005/30140, 2005, A2. Location in patent: Page/Page column 205
[4] European Journal of Medicinal Chemistry, 2017, vol. 140, p. 212 - 228