Hydrochloric Acid → N-(1-Cyclopropanesulfonylaminocarbonyl-2-vinyl-cyclopropyl)-2-(hex-5-enyl-methyl-amino-carbonyl)-4-hydroxy-cyclopentane-carboxamide

Participants

Role	Name	HCID	Charge
Reactant	Hydrochloric Acid	HCID 313	—
Reactant	Lithium Hydroxide	HCID 3939	—
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	(1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide hydrochloride	HCID 23595124	—
Reactant	3-Oxo-2-oxa-bicyclo[2.2.1]heptane-5-carboxylic acid hex-5-enyl-methylamide	HCID 59165488	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N-(1-Cyclopropanesulfonylaminocarbonyl-2-vinyl-cyclopropyl)-2-(hex-5-enyl-methyl-amino-carbonyl)-4-hydroxy-cyclopentane-carboxamide	HCID 68589808	66%

Reaction Steps

LiOH solution (0.15M, 53 mL, 8 mmol) was added to the lactone amide 24a (996 mg, 3.96 mmol) in an ice bath and stirred for 1 h. The mixture was acidified to pH 2-3 with 1N HCl and evaporated, co-evaporated with toluene several times, and dried under vacuum overnight. (1R,2S)-cyclopropanesulfonic acid (1-amino-2-vinyl-cyclopropane-carbonyl)amide hydrochloride (4.21 mmol) and HATU (1.78 g, 4.68 mmol) were added. The mixture was cooled in an ice bath under argon, DMF (25 mL) and then DIEA (2.0 mL, 11.5 mmol) were added. After stirring for 30 min, the mixture was stirred at rt for 3 h. After evaporation of solvent, the residue was dissolved in EtOAc (120 mL), washed successively with 0.5 N HCl (20 mL) and saturated NaCl (2×20 mL), and dried over Na2SO4. Flash column chromatography (200 g YMC silica gel, 2-4% MeOH in CH2Cl2 gave white solids (1.25 g, 66%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08937080B2
Source dataset	uspto-grants-2015_01
ORD ID	ord-1165a538880744a7af15c80b41c13e9e
Source note	uspto-grants-2015_01