Diisopropylethylamine → 3-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(2-(2,2-difluoroethylamino)-2-oxoethyl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxamide

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-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid	HCID 71471635	—
Reactant	2-aMino-N-(2,2-difluoroethyl)acetaMide hydrochloride	HCID 86693750	—
Solvent	Acetonitrile	HCID 6342	—
Product	3-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(2-(2,2-difluoroethylamino)-2-oxoethyl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxamide	HCID 71472566	88%

Reaction Steps

To a solution of compound 3-[5-(3,5-dichloro-4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid (3 g, 6.4 mmol) in acetonitrile (30 mL) is added N,N-diisopropylethylamine (2.5 g, 19 mmol), 2-amino-N-(2,2-difluoro-ethyl)-acetamide hydrochloride (1.34 g, 7.7 mmol) and HATU (3.7 g, 9.6 mmol), after the addition the mixture is stirred at room temperature for 1 hour. After being detected by TLC and LCMS, the reaction mixture is concentrated and the residue is purified by column chromatography to afford desired product (3 g, 88%). MS (m/z): 588.1 (M+1).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09255111B2
Source dataset	uspto-grants-2016_02
ORD ID	ord-2ce3dcd83a2745aca443b9b6dd87bfe7
Source note	uspto-grants-2016_02