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

HRID 646930Notes

Reaction equation

HRID 646930 reaction equation
Br[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH:11]([CH3:14])[CH2:10][CH2:9]2)[C:5]([N+:15]([O-:17])=[O:16])=[CH:4][CH:3]=1.[CH2:18]([O:25][C:26]([N:28]1[CH2:33][CH2:32][NH:31][C:30](=[O:34])[CH2:29]1)=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>C1(C)C=CC=CC=1.[Cu]I>[CH2:18]([O:25][C:26]([N:28]1[CH2:33][CH2:32][N:31]([C:2]2[N:7]=[C:6]([N:8]3[CH2:13][CH2:12][CH:11]([CH3:14])[CH2:10][CH2:9]3)[C:5]([N+:15]([O-:17])=[O:16])=[CH:4][CH:3]=2)[C:30](=[O:34])[CH2:29]1)=[O:27])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 736777Benzyl 3-oxopiperazine-1-carboxylateHCID 586384926'-Bromo-4-methyl-3'-nitro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl

Product 1

HCID 686819054-(4-Methyl-3'-nitro-3,4,5,6-tetrahydro-2h-[1,2']bipyridinyl-6'-yl)-3-oxo-piperazine-1-carboxylic acid benzyl esterYield 57%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-f83c52a281c946d4b696f008af02118c
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Reaction notes

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