1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (5S,12S,16S)-tri-tert-butyl 5-(4-(bis((1-(2-(bis(2-tert-butoxy-2-oxo ethyl)amino)-2-oxo ethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate

Participants

Role	Name	HCID	Charge
Reactant	1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide	HCID 15908	—
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1,5-Bis(1,1-dimethylethyl) N-((((1S)-5-amino-1-((1,1-dimethylethoxy)carbonyl)pentyl)amino)carbonyl)-L-glutamate	HCID 25194225	—
Reactant	2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)hexanoic acid	HCID 78112781	—
Solvent	Dichloromethane	HCID 6344	—
Product	(5S,12S,16S)-tri-tert-butyl 5-(4-(bis((1-(2-(bis(2-tert-butoxy-2-oxo ethyl)amino)-2-oxo ethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate	HCID 86643307	—

Reaction Steps

A solution of (S)-di-tert-butyl 2-(3-((S)-6-amino-1-tert-butoxy-1-oxohexan-2-yl)ureido)pentanedioate (97 mg, 0.20 mmol), 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)hexanoic acid (132 mg, 0.12 mmol), EDCI (38 mg, 0.20 mmol), HOBt (26 mg, 0.20) and DIPEA (0.30 mL) in DCM (5.0 mL) was stirred at rt for 2 days. The reaction mixture was purified by biotage eluting with 1% MeOH in DCM to afford (5S,12S,16S)-tri-tert-butyl 5-(4-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate (impure) as an oil.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09433594B2
Source dataset	uspto-grants-2016_09
ORD ID	ord-903e6a7fc0cd4f11bfc496aef4c4f938
Source note	uspto-grants-2016_09