Diisopropylethylamine → (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)docosa-4,7,10,13,16,19-hexaenamide

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Lenalidomide	HCID 216326	—
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	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Acetonitrile	HCID 6342	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	(4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)docosa-4,7,10,13,16,19-hexaenamide	HCID 70945158	63.7%

Reaction Steps

Lenalidomide (200 mg, 0.771 mmol) was taken up in 5 mL of CH3CN and 2 mL of DMF along with (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid (DHA, 253 mg, 0.771 mmol), HATU (322 mg, 0.848 mmol) and DIEA (200 μL, 2.3 mmol). The resulting reaction mixture was stirred at room temperature for 3 h and diluted with EtOAc (20 mL). The organic layer was washed with water (3×5 mL), brine, dried (Na2SO4) and concentrated under reduced pressure. Purification by silica gel chromatography (95% CH2Cl2, 5% MeOH) afforded 280 mg of (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)docosa-4,7,10,13,16,19-hexaenamide (63%). MS (EI) calculated for C35H43N3O4: 569.33; found: [M+H]+ 570.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09029548B2
Source dataset	uspto-grants-2015_05
ORD ID	ord-9f63894673be47dd8594244af616f9da
Source note	uspto-grants-2015_05