Water → 3,5-dichloro-N-(4-fluorobenzyl)-N-(3-((4-fluorobenzylamino)methyl)benzyl)-2-hydroxybenzamide

Participants

Role	Name	HCID	Charge
Reactant	Water	HCID 962	—
Reactant	3,5-Dichlorosalicylic acid	HCID 9445	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	(4-Fluoro-benzyl)-{3-[(4-fluoro-benzylamino)-methyl]-benzyl}-amine	HCID 66616478	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	1-Hydroxybenzotriazole	HCID 75771	—
Product	3,5-dichloro-N-(4-fluorobenzyl)-N-(3-((4-fluorobenzylamino)methyl)benzyl)-2-hydroxybenzamide	HCID 66616499	21.4%

Reaction Steps

To a solution of 3,5-dichloro-2-hydroxybenzoic acid (300 mg, 1.449 mmol) in DMF (5 mL) at rt was added EDCI.HCl (300 mg, 1.565 mmol) followed by N,N′-(1,3-phenylenebis(methylene))bis(1-(4-fluorophenyl)methanamine) (365 mg, 1.036 mmol) in 2 mL of DMF and hydrated HOBt.H2O (200 mg), and the reaction mixture was stirred at rt overnight. The mixture was directly purified by prep HPLC to provide a monoacylated product 3,5-dichloro-N-(4-fluorobenzyl)-N-(3-((4-fluorobenzylamino)methyl)benzyl)-2-hydroxybenzamide (0.12 g, 21.4%) and a diacylated product, N,N′-(1,3-phenylenebis(methylene))bis(3,5-dichloro-N-(4-fluorobenzyl)-2-hydroxybenzamide) (0.245 g, 32.4%). 1H NMR (CD3OD): δ 7.34˜6.80 (m, 16H), 4.59 (s, 4H), 4.24 (s, 4H); MS (ESI): (M+H)+=731.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08501992B2
Source dataset	uspto-grants-2013_08
ORD ID	ord-248c6a1ea86c4112981d45c9970965f6
Source note	uspto-grants-2013_08