Cyclopropaneacetic acid → N-((1-(2-(2-cyclopropylacetamido)ethyl)piperidin-4-yl)methyl)-3,5-bis(trifluoromethyl)benzamide

Participants

Role	Name	HCID	Charge
Reactant	Cyclopropaneacetic acid	HCID 138440	—
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	N-((1-(2-aminoethyl)piperidin-4-yl)methyl)-3,5-bis(trifluoromethyl)benzamide	HCID 57993201	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Dichloromethane	HCID 6344	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	N-((1-(2-(2-cyclopropylacetamido)ethyl)piperidin-4-yl)methyl)-3,5-bis(trifluoromethyl)benzamide	HCID 57993477	—

Reaction Conditions

Temperature	-20 °C

Reaction Steps

A solution of N-((1-(2-aminoethyl)piperidin-4-yl)methyl)-3,5-bis(trifluoromethyl)benzamide (70 mg, 0.18 mmol), TEA (123 μL, 0.881 mmol), and 2-cyclopropylacetic acid (35 mg, 0.35 mmol) in a 1:1 mixture of CH2Cl2:DMF (2 mL) was treated with a solution of HATU (100 mg, 0.264 mmol) in DMF (1 mL). The reaction was stirred over night then transferred to a test tube containing saturated aqueous NaHCO3 (4 mL) and EtOAc (4 mL). The biphasic mixture was mixed vigorously and allowed to separate for 15 min. After separation, the mixture was cooled to −20° C. until the aqueous layer was frozen. The organic layer was then poured off and the solvent was removed under reduced pressure at 50° C. The resulting residue was purified by HiTOPs.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08569344B2
Source dataset	uspto-grants-2013_10
ORD ID	ord-3527751f2926492cb939677e21e54a1f
Source note	uspto-grants-2013_10