1-Hydroxybenzotriazole → 4-{2-[(Biphenyl-4-carbonyl)-amino]-acetyl}-piperazine-1-carboxylicacid tert-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	tert-Butyl piperazine-1-carboxylate	HCID 143452	—
Reactant	2-((4-Phenylphenyl)formamido)acetic acid	HCID 262943	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Solvent	Water	HCID 962	—
Solvent	Dimethylformamide	HCID 6228	—
Product	4-{2-[(Biphenyl-4-carbonyl)-amino]-acetyl}-piperazine-1-carboxylicacid tert-butyl ester	HCID 31122191	37.5%

Reaction Steps

DIPEA (2.928 g, 22.66 mmol) was added to a stirred solution of [(biphenyl-4-carbonyl)-amino]-acetic acid (2.892 g, 11.33 mmol) in DMF (30 mL). HOBT (1.835 g, 13.59 mmol) and EDCI.HCl (2.532 g, 13.59 mmol) were then added at room temperature. After 2 minutes, N-Boc-piperazine (3.381 g, 24.22 mmol) was added and the resulting mixture was stirred overnight. The reaction mixture was diluted with cold water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine solution, dried over sodium sulphate and concentrated in vacuo to afford 1.7 g (37.5% yield) of 4-{2-[(biphenyl-4-carbonyl)-amino]-acetyl}-piperazine-1-carboxylicacid tert-butyl ester. LC-MS purity: 82.06%

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07842696B2
Source dataset	uspto-grants-2010_11
ORD ID	ord-181c411793724ecdb0d068be326261a3
Source note	uspto-grants-2010_11