4-Amino-6-chloropyrimidine → 4-(6-Chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester

HRID 1020025Notes

Reaction equation

HRID 1020025 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](Cl)=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:20][C:21]1[CH:26]=[C:25]([Cl:27])[N:24]=[CH:23][N:22]=1>CN(C1C=CN=CC=1)C.ClCCl>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=[O:18])[NH:20][C:21]2[CH:26]=[C:25]([Cl:27])[N:24]=[CH:23][N:22]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 2380124-Amino-6-chloropyrimidineHCID 2776270Benzyl 4-(chlorocarbonyl)piperidine-1-carboxylate

Product 1

HCID 595089554-(6-Chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl esterYield 97.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-chlorocarbonyl-piperidine-1-carboxylic acid benzyl ester (VII) (5.70 g, 20.2 mmol), 4-amino-6-chloropyrimidine (I) (2.10 g, 16.2 mmol) and 4-(N,N-dimethylamino)-pyridine (2.90 g, 23.7 mmol) in dichloromethane (50 ml) was heated to reflux temperature for 18 hours. The progress of the reaction was monitored by TLC, then dichloromethane was completely distilled off. Aqueous sodium bicarbonate solution was added to the residue and the mixture was extracted with ethyl acetate (3×100 ml). The organic layers were separated, dried over sodium sulfate and concentrated to obtain 4-(6-chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester (VIII) (5.9 g, 79%) as a yellow solid.

Workup

  1. temperaturewas heated
  2. temperatureto reflux temperature for 18 hours
  3. distillationdichloromethane was completely distilled off
  4. additionAqueous sodium bicarbonate solution was added to the residue
  5. extractionthe mixture was extracted with ethyl acetate (3×100 ml)
  6. customThe organic layers were separated
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-a2034e20e03a4e02a6575777a452b1ec
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Reaction notes

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