Hydrochloric Acid → (E)-methyl 4-(2-(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenamidoethylamino)-4-oxobut-2-enoate

Participants

Role	Name	HCID	Charge
Reactant	Hydrochloric Acid	HCID 313	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Doconexent	HCID 445580	—
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-(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenamidoethylamino)-4-oxobut-2-enoate	HCID 53255264	35.8%

Reaction Steps

The HCl salt of (E)-methyl 4-(2-aminoethylamino)-4-oxobut-2-enoate (8.1 mmol) was takes up in 40 mL of CH3CN along with (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid (DHA, 2.60 g, 8.1 mmol), HATU (3.4 g, 12.1 mmol) and DIEA (4.2 mL). The reselling 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 1.4 g of (E)-methyl 4-(2-(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenamidoethylamino)-4-oxobut-2-enoate. MS (EI) calcd for C29H42N2O4: 482.31; found 483 (M+1).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09289503B2
Source dataset	uspto-grants-2016_03
ORD ID	ord-d9f6d49a180b47b1b362ef229b6c33e1
Source note	uspto-grants-2016_03