Diisopropylethylamine → (2S,4R)-methyl 4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)-1-((S)-3,3-dimethyl-2-((((1R,2R)-2-(pent-4-en-1-yl)cyclopropoxy)carbonyl)amino)butanoyl)pyrrolidine-2-carboxylate

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	L-Valine, 3-methyl-N-[[[(1R,2R)-2-(4-penten-1-yl)cyclopropyl]oxy]carbonyl]-	HCID 59287076	—
Reactant	Methyl (2S)-4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)pyrrolidine-2-carboxylate hydrochloride	HCID 78358295	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	(2S,4R)-methyl 4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)-1-((S)-3,3-dimethyl-2-((((1R,2R)-2-(pent-4-en-1-yl)cyclopropoxy)carbonyl)amino)butanoyl)pyrrolidine-2-carboxylate	HCID 78358296	96%

Reaction Conditions

Temperature	20 °C

Reaction Steps

A solution (0.2 M) of methyl (4R)-4-[(3-chloro-7-methoxyquinoxalin-2-yl)oxy]-L-prolinate hydrochloride in DMF was treated with 3-methyl-N-({[(1R,2R)-2-pent-4-en-1-ylcyclopropyl]oxy}carbonyl)-L-valine (1.1 eq), DIEA (5 eq) and HATU (1.2 eq). The resulting mixture was stirred at 20° C. for 5 h, then diluted with EtOAc. The organic layer was separated and washed with aqueous HCl (1 N), saturated aqueous NaHCO3 and brine. The dried organic phase was concentrated under reduced pressure to give a residue that was purified by flash chromatography (eluent 10-30% EtOAc/petroleum ether) to furnish the title compound (96%) as an oil. MS (ES+) m/z 604 (M+H)+

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07973040B2
Source dataset	uspto-grants-2011_07
ORD ID	ord-95eae81013b14d80bc711c1bfcbc8d1b
Source note	uspto-grants-2011_07