N,N'-Dimethylethylenediamine → (+/-)-(E)-2-(7-chloro-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)-N-methyl-N-(2-(methylamino)ethyl)acetamide

Participants

Role	Name	HCID	Charge
Reactant	N,N'-Dimethylethylenediamine	HCID 8070	—
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	(+/-)-(E)-2-(7-bromo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)acetic acid	HCID 58295679	—
Solvent	Dichloromethane	HCID 6344	—
Product	(+/-)-(E)-2-(7-chloro-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)-N-methyl-N-(2-(methylamino)ethyl)acetamide	HCID 44226675	18.2%

Reaction Steps

A vial was charged with (±)-(E)-2-(7-bromo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)acetic acid (5 mg, 0.01 mmol), N,N′-dimethylethylenediamine (0.007 mL, 0.066 mmol), HOBt (3 mg, 0.02 mmol), i-Pr2NEt (0.006 mL, 0.032 mmol) and CH2Cl2 (1 mL). EDC.HCl (4 mg, 0.021 mmol) was added. The mixture was stirred at rt for 1 d and evaporated to dryness. The residue was purified by preparative HPLC to afford (±)-(E)-2-(7-chloro-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)-N-methyl-N-(2-(methylamino)ethyl)acetamide (1.0 mg, 14%). LC-MS Method 1 tR=1.55, min, m/z=548, 550.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08383629B2
Source dataset	uspto-grants-2013_02
ORD ID	ord-5b7719cb6d3344a0a38763a20bf533e5
Source note	uspto-grants-2013_02