Hydrochloric Acid → (E)-methyl 4-(2-(5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentaenamidoethylamino)-4-oxobut-2-enoate

Participants

Role	Name	HCID	Charge
Reactant	Hydrochloric Acid	HCID 313	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Icosapent	HCID 446284	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	(E)-methyl 4-(2-aminoethylamino)-4-oxobut-2-enoate	HCID 86655426	—
Solvent	Acetonitrile	HCID 6342	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	(E)-methyl 4-(2-(5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentaenamidoethylamino)-4-oxobut-2-enoate	HCID 53339944	89.4%

Reaction Steps

The HCl salt of (E)-methyl 4-(2-aminoethylamino)-4-oxobut-2-enoate (0.735 mmol) was taken up in 40 mL of CH3CN along with (5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentaenoic acid (EPA, 222 mg, 0.735 mmol), HATU (307 mg, 0.81 mmol) and DIEA (380 μL). The resulting reaction mixture was stirred at room temperature for 2 h and diluted with EtOAc. The organic layer was washed with saturated aqueous NaHCO3, brine, dried (Na2SO4) and concentrated under reduced pressure. Purification by chromatography (95% CH2Cl2, 5% MeOH) afforded 300 mg of (E)-methyl 4-(2-(5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentaenamidoethylamino)-4-oxobut-2-enoate (89% yield). MS (EI) calcd for C23H40N2O4: 456.3; found: 457 (M+1).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09289503B2
Source dataset	uspto-grants-2016_03
ORD ID	ord-fb6da85e632847dd88e3484583491346
Source note	uspto-grants-2016_03