2,6-Lutidine → Tert-Butyl(2R,5R)-2,5-bis {2-[2-({(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenyl propanoyl}amino)phenyl]ethyl}morpholine-4-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	2,6-Lutidine	HCID 7937	—
Reactant	Sodium Bicarbonate	HCID 516892	—
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	(S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acid	HCID 10017620	—
Reactant	tert-Butyl(2R,5R)-5-[2-(2-aminophenyl)ethyl]-2-{2-[2-({(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenylpropanoyl}amino)phenyl]ethyl}morpholine-4-carboxylate	HCID 86726326	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	Tert-Butyl(2R,5R)-2,5-bis {2-[2-({(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenyl propanoyl}amino)phenyl]ethyl}morpholine-4-carboxylate	HCID 86726328	—

Reaction Steps

(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenylpropanoic acid (1.2 equiv), HATU (1.4 equiv) and 2,6-lutidine (2.0 equiv) were combined in DMF (0.2 M vs aniline). tert-Butyl(2R,5R)-5-[2-(2-aminophenyl)ethyl]-2-{2-[2-({(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenylpropanoyl}amino)phenyl]ethyl}morpholine-4-carboxylate (1.0 equiv) was dissolved in DMF (0.11 M) and was added to the reaction mixture. The reaction was stirred at room temperature for 18 h and ethyl acetate and saturated sodium bicarbonate were added. Aqueous layer was extracted twice with ethyl acetate and combined organic layers were washed with brine, 10% aqueous lithium chloride, 1N HCl, brine, dried (Na2SO4), filtered and concentrated. The crude product was purified using automated silica-gel flash chromatography using a solvent gradient of 5% to 60% of ethyl acetate and hexanes.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09315475B2
Source dataset	uspto-grants-2016_04
ORD ID	ord-606c0d31f8ca4b5ea9d7ee20c554f6ab
Source note	uspto-grants-2016_04