N,N'-Dimethylethylenediamine → 4-(4-Methyl-3'-nitro-3,4,5,6-tetrahydro-2h-[1,2']bipyridinyl-6'-yl)-3-oxo-piperazine-1-carboxylic acid benzyl ester

To a solution of 6′-bromo-4-methyl-3′-nitro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl (as prepared in the previous step) (300 mg, 1.00 mmol) in toluene (5 mL) was added 3-oxo-piprazine-1-carboxylic acid benzyl ester (351 mg, 1.50 mmol), K3PO4 (424 mg, 2.00 mmol) and CuI (38 mg, 0.20 mmol) followed by N,N′-dimethylethylenediamine (20 μL, 0.18 mmol) under Ar. The resulting mixture was heated at reflux overnight. The reaction mixture was allowed to cool to room temperature and filtered through a thin pad of Celite. The filtrate was concentrated in vacuo and the residue obtained was purified by chromatography on silica (20% EtOAc:hexane) to obtain 4-(4-methyl-3′-nitro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-6′-yl)-3-oxo-piperazine-1-carboxylic acid benzyl ester (258 mg, 57%). This compound (453 mg, 1.00 mmol) was dissolved in 30% HBr/HOAc (1 mL). The resulting mixture was stirred at room temperature overnight and Et2O (20 mL) was added dropwise. The resulting mixture was stirred for another hour, the precipitated hydrobromide was collected by suction filtration, washed with Et2O (3×20 mL), dried in vacuo for 1 h and used directly in next step.

1. temperatureThe resulting mixture was heated
2. temperatureat reflux overnight
3. filtrationfiltered through a thin pad of Celite
4. concentrationThe filtrate was concentrated in vacuo
5. customthe residue obtained
6. customwas purified by chromatography on silica (20% EtOAc:hexane)

ORD-Eintrag

ord-f83c52a281c946d4b696f008af02118c

Quelldatensatz

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07705042B2