N,N'-Dimethylethylenediamine → HCID 66877639, compound

HRID 923118Notes

Reaction equation

HRID 923118 reaction equation
I[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.[C:12]([N:19]1[CH2:24][CH2:23][NH:22][C:21](=[O:25])[CH2:20]1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].C(=O)([O-])[O-].[K+].[K+].CNCCNC>C1(C)C=CC=CC=1.C(OCC)(=O)C.[Cu](I)I>[CH3:9][O:8][C:6]([C:5]1[CH:10]=[CH:11][C:2]([N:22]2[CH2:23][CH2:24][N:19]([C:12]([O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:13])[CH2:20][C:21]2=[O:25])=[CH:3][CH:4]=1)=[O:7]

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 69273Methyl 4-iodobenzoateHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylate

Product 1

HCID 66877639HCID 66877639, compound

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 1 g of methyl 4-iodobenzoate, 920 mg of 4-Boc-piperazinone, 1.1 g of potassium carbonate, 32 mg of N,N′-dimethylethylenediamine and 70 mg of copper iodide in 10 mL of toluene was heated to 150° C. in a sealed microwave reactor for 3 h. The reaction mixture was diluted with ethyl acetate, washed with H2O, dried (MgSO4) and evaporated. Purified by silica gel chromatography (20-80% ethyl acetate/hexane) to afford tert-butyl 4-(4-(methoxycarbonyl)phenyl)-3-oxopiperazine-1-carboxylate. 500 mg of tert-butyl 4-(4-(methoxycarbonyl)phenyl)-3-oxopiperazine-1-carboxylate was hydrolyzed via Procedure M to give 4-(4-(tert-buthoxycarbonyl)-2-oxopiperazin-1-yl)benzoic acid. 100 mg of 4-chloro-3-(pyridin-2-yl)aniline was coupled to 4-(4-(tert-buthoxycarbonyl)-2-oxopiperazin-1-yl)benzoic acid via Procedure G. The reaction mixture was diluted with ethyl acetate, washed with 0.1 N sodium hydroxide and brine, dried (MgSO4) and evaporated to afford tert-butyl 4-(4-(4-chloro-3-(pyridin-2-yl)phenylcarbamoyl)phenyl)-3-oxopiperazine-1-carboxylate. 300 mg of crude tert-butyl 4-(4-(4-chloro-3-(pyridin-2-yl)phenylcarbamoyl)phenyl)-3-oxopiperazine-1-carboxylate was treated with TFA (2 mL) containing trace amounts of H2O for 1 h. The reaction mixture was evaporated and the crude product was purified by reverse phase HPLC to yield N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(2-oxopiperazin-1-yl)benzamide. MS (Q1) 407.3 (M)+.

Workup

  1. washwashed with H2O
  2. dry with materialdried (MgSO4)
  3. customevaporated
  4. customPurified by silica gel chromatography (20-80% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-16001e05e3454aa9af5144690bd99bf8
Source dataset
uspto-grants-2016_03
Patent number
US09278961B2

Reaction notes

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