Water → Tert-butyl 4-[2'-(2-{[(cyanomethyl)amino]carbonyl}-4-methylpentyl)[1,1'-biphenyl]-4-yl]-1-piperazinecarboxylate

Participants

Role	Name	HCID	Charge
Reactant	Water	HCID 962	—
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	4-(4-BOC-Piperazino)phenylboronic acid	HCID 5233014	—
Reactant	2-(2-bromobenzyl)-N-(cyanomethyl)-4-methylpentanamide	HCID 22236189	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Dimethylformamide	HCID 6228	—
Product	Tert-butyl 4-[2'-(2-{[(cyanomethyl)amino]carbonyl}-4-methylpentyl)[1,1'-biphenyl]-4-yl]-1-piperazinecarboxylate	HCID 22235962	—

Reaction Conditions

Temperature	90 °C

Reaction Steps

To 2-(2-bromobenzyl)-N-(cyanomethyl)-4-methylpentanamide (260 mg, 0.805 mmol) and 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (275 mg, 0.886 mmol) in DMF (10 mL) under dry nitrogen was added aqueous sodium carbonate (2 M, 1.2 mL, 2.42 mmol) followed by the catalyst PdCl2(dppf) (25 mg, 0.025 mmol). The reaction was heated to 90° C. for 0.5 hours and more PdCl2(dppf) (25 mg, 0.025 mmol) was added and the reaction mixture was heated for another 4 hours. Water was added and the product extracted with ether (2×), dried over Na2SO4, concentrated in vacuo, and purified by flash chromatography over silica gel (EtOAc/Hex, 35/65) to afford tert-butyl 4-[2′-(2-{[(cyanomethyl)amino]carbonyl}-4-methylpentyl)[1,1 ′-biphenyl]-4-yl]-1-piperazinecarboxylate.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07012075B2
Source dataset	uspto-grants-2006_03
ORD ID	ord-7a6f68e372b1441dbc2a21c8b365f9e8
Source note	uspto-grants-2006_03