L-Proline → 4-[1,8]Naphthyridin-2-yl-piperidine-1-carboxylic acid benzyl ester

HRID 1424322Notes

Reaction equation

HRID 1424322 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=O)[CH3:18])[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[C:26]([CH:27]=O)=[CH:25][CH:24]=[CH:23][N:22]=1.N1CCC[C@H]1C(O)=O>C(O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[CH:18]=[CH:27][C:26]3[C:21](=[N:22][CH:23]=[CH:24][CH:25]=3)[N:20]=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 3

HCID 145742L-ProlineHCID 7376333-Pyridinecarboxaldehyde, 2-amino-HCID 19065050Benzyl 4-acetylpiperidine-1-carboxylate

Product 1

HCID 690813314-[1,8]Naphthyridin-2-yl-piperidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

100 mg (0.383 mmol) ketone (21), 47 mg (0.383 mmol) 2-aminopyridine-3-carbaldehyde and 22 mg (0.192 mmol) proline were refluxed in ethanol for 3 days. The solvent was removed under reduced pressure. The crude product was purified by chromatography on silica gel (ethyl acetate/hexane) to yield 4-[1,8]naphthyridin-2-yl-piperidine-1-carboxylic acid benzyl ester as an oil. 210 mg (0,605 mmol) of this intermediate were dissolved together with 50 mg 10% Pd/C in 50 ml methanol and stirred under an atmosphere of hydrogen for 18 h. Removal of the catalyst by filtration through a pad of Celite followed by evaporation of the solvent under reduced pressure gave the desired amine (22).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customThe crude product was purified by chromatography on silica gel (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9ea548d1ca0945a48468bd02313d49d4
Source dataset
uspto-grants-2015_01
Patent number
US08927534B2

Reaction notes

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