Diisopropylethylamine → N-[(1S,2S,4R)-1-Benzyl-4-(3,3-dimethyl-butylcarbamoyl)-2-hydroxypenty]-3,5-bis-(2-oxo-pyrrolidin-1-yl)benzamide

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
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	3,5-bis(2-oxopyrrolidin-1-yl)benzoic Acid	HCID 11162023	—
Reactant	(2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)-amide	HCID 68890142	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N-[(1S,2S,4R)-1-Benzyl-4-(3,3-dimethyl-butylcarbamoyl)-2-hydroxypenty]-3,5-bis-(2-oxo-pyrrolidin-1-yl)benzamide	HCID 10196800	64.2%

Reaction Steps

To a solution of (2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)amide (D2) (46 mg, 0.145 mmol) in DMF (2 ml) was added iPr2NEt (61 μl, 0.348 mmol) followed by 3,5-bis-2-oxopyrrolidin-1-yl)benzoic acid (D8) (50 mg, 0.174 mmol) and HATU (77 mg, 0.203 mmol). The reaction mixture was stirred at room temperature for 6 hours. The solvent was evaporated to dryness and the residue was partitioned between 0.5 M HCl and DCM. The organic phase was separated and washed with NaHCO3, brine and dried over MgSO4, filtered and evaporated to afford the crude product (61 mg) as yellow oil. The product was triturated in petroleum/diethylether which yielded E5 (55 mg) as a yellow solid.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US06992103B2
Source dataset	uspto-grants-2006_01
ORD ID	ord-0c83f70b4df6449f8907273222652b61
Source note	uspto-grants-2006_01