1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-[6-(2-Ethoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1020027Notes

Reaction equation

HRID 1020027 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH2:38]([O:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[C:47]1[N:52]=[CH:51][N:50]=[C:49]([NH2:53])[CH:48]=1)[CH3:39]>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14](=[O:16])[NH:53][C:49]2[CH:48]=[C:47]([C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=3[O:40][CH2:38][CH3:39])[N:52]=[CH:51][N:50]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 595089836-(2-Ethoxyphenyl)pyrimidin-4-amine

Product 1

HCID 595089574-[6-(2-Ethoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl esterYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (V), (1.27 g, 5.54 mmol) in dry dichloromethane, HOBt (1.27 g, 9.30 mmol) and EDCI (1.78 g, 9.30 mmol) were added at 0° C. and the reaction mixture was stirred for 5-10 minutes. Then 6-(2-ethoxy-phenyl)-pyrimidin-4-ylamine (III) (1.00 g, 4.65 mmol) was added and the reaction mixture was heated to reflux under an atmosphere of nitrogen for 48 hours. The reaction mixture was diluted with dichloromethane and washed with 1N HCl, aqueous sodium bicarbonate, water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the crude product was purified by column chromatography to obtain 4-[6-(2-ethoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester (IV) (0.79 g, 40%).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux under an atmosphere of nitrogen for 48 hours
  3. washwashed with 1N HCl, aqueous sodium bicarbonate, water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-61ee97484cd54488a6f3bbe7ed8aa71d
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Reaction notes

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