5-((Z)-(5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid Chemical Properties

Melting point:

320 °C (decomp)

Boiling point:

588.4±50.0 °C(Predicted)

Density 

1.454±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

solubility 

Aqueous Base (Slightly, Heated), DMSO (Slightly, Heated)

form 

Solid

pka

5.79±0.50(Predicted)

color 

Dark Orange

InChI

InChI=1S/C16H13FN2O3/c1-7-13(18-8(2)14(7)16(21)22)6-11-10-5-9(17)3-4-12(10)19-15(11)20/h3-6,18H,1-2H3,(H,19,20)(H,21,22)/b11-6-

InChIKey

RBHBOUYXUXWCNJ-WDZFZDKYSA-N

SMILES

N1C(/C=C2/C3=C(NC/2=O)C=CC(F)=C3)=C(C)C(C(O)=O)=C1C

5-((Z)-(5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid Usage And Synthesis

Chemical Properties

Brown crystals

Uses

Des-N-(2-Diethylaminoethyl)amide Sunitinib Acid is an impurity of Sunitinib (S819995), a multi-kinase inhibitor targeting several receptor tyrosine kinases (RTK). Antineoplastic.

Synthesis

Ammonium sulfate ((NH4)2SO4, 0.09 g, 0.67 mmol) was added to hexamethyldisilazane (HMDS, 20 mL) as 2,4-dimethyl-5-formyl-1H-pyrrole-3-carboxylic acid (8, 1.0 g, 6.61 mmol) and 5-fluoroindol-2-one (14, 1.1 g, 3.77 mmol) at room temperature in a stirred mixture. Subsequently, the reaction mixture was heated to reflux and maintained at this temperature for at least 5 h. The reaction process was monitored by gas chromatography (GC). Upon completion of the reaction, 5-fluoroindol-2-one (14) and trimethylsilyl trifluoromethanesulfonate (TMSOTf, 0.29 g, 1.32 mmol) were added. Stirring of the mixture was continued until high performance liquid chromatography (HPLC) analysis showed that the reaction was complete. The reaction mixture was quenched with water (6 mL) and acetonitrile (MeCN, 30 mL), filtered and the filter cake was washed sequentially with acetonitrile (20 mL) and ethanol (EtOH, 5 mL). Finally, the product was dried under vacuum at 40 °C overnight to afford the target compound 5-((Z)-(5-fluoro-2-oxoindolidine-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (15, 1.92 g, 97% yield) as a yellow to brown powder with an HPLC purity of about 82.1%.

References

[1] Patent: US2013/190512, 2013, A1. Location in patent: Paragraph 0088
[2] Patent: WO2007/81560, 2007, A2. Location in patent: Page/Page column 6
[3] Patent: WO2006/127961, 2006, A1. Location in patent: Page/Page column 15-16
[4] Patent: WO2008/33562, 2008, A2. Location in patent: Page/Page column 34
[5] Patent: US2009/76005, 2009, A1. Location in patent: Page/Page column 12; 13