Trifluoroacetic acid → (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-(2,5-dioxo-2H-pyrrol-1(5H)-yl)ethyl)docosa-4,7,10,13,16,19-hexaenamide

Participants

Role	Name	HCID	Charge
Reactant	Trifluoroacetic acid	HCID 6422	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Doconexent	HCID 445580	—
Reactant	N-(2-Aminoethyl)maleimide	HCID 2778791	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Solvent	Acetonitrile	HCID 6342	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	(4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-(2,5-dioxo-2H-pyrrol-1(5H)-yl)ethyl)docosa-4,7,10,13,16,19-hexaenamide	HCID 58348976	70.6%

Reaction Steps

The TFA salt of 1-(2-aminoethyl)-1H-pyrrole-2,5-dione (Aldrich, 280 mg, 1.10 mmol) was taken up in 10 mL of CH3CN along with (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid (DHA, 360 mg, 1.1 mmol), HATU (460 mg, 1.2 mmol) and DIEA (0.58 mL). The resulting reaction mixture was stirred at room temperature for 3 h. It was then diluted with EtOAc and washed successively with saturated aqueous NaHCO3 and brine. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. Purification by chromatography (CH2Cl2) afforded 350 mg of (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-(2,5-dioxo-2H-pyrrol-1(5H)-yl)ethyl)docosa-4,7,10,13,16,19-hexaenamide (70% yield).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09289503B2
Source dataset	uspto-grants-2016_03
ORD ID	ord-c5c2c63da544479ab7b18dbdbf39a652
Source note	uspto-grants-2016_03