4-[6-(2-Benzyloxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester → Piperidine-4-carboxylic acid [6-(2-benzyloxy-phenyl)-pyrimidin-4-yl]-amide

HRID 1020042Notes

Reaction equation

HRID 1020042 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=[O:39])[NH:18][C:19]2[CH:24]=[C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[N:22]=[CH:21][N:20]=2)[CH2:13][CH2:12]1)=O)C1C=CC=CC=1>Br.C(O)(=O)C>[CH2:32]([O:31][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[C:23]1[N:22]=[CH:21][N:20]=[C:19]([NH:18][C:17]([CH:14]2[CH2:15][CH2:16][NH:11][CH2:12][CH2:13]2)=[O:39])[CH:24]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

4

Reactant 1

HCID 595091004-[6-(2-Benzyloxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 59509063Piperidine-4-carboxylic acid [6-(2-benzyloxy-phenyl)-pyrimidin-4-yl]-amideYield 7.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 260Hydrogen BromideSolvent

Procedure

4-[6-(2-Benzyloxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester (XVI) (0.5 g, 1 mmol) was dissolved in 33% HBr in acetic acid (3 ml) and stirred at room temperature for 45 minutes. A yellow solid precipitated out; the reaction mixture was quenched at 0° C. with aqueous sodium hydroxide solution and extracted with ethyl acetate (3×10 ml). The organic phases were separated, combined, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by preparative HPLC (C-18, AcN:H2O with 0.05% TFA) and lyophilized to afford piperidine-4-carboxylic acid [6-(2-benzyloxy-phenyl)-pyrimidin-4-yl]-amide (compound #9A) (0.028 g, 7%) as a white solid.

Workup

  1. customA yellow solid precipitated out
  2. customthe reaction mixture was quenched at 0° C. with aqueous sodium hydroxide solution
  3. extractionextracted with ethyl acetate (3×10 ml)
  4. customThe organic phases were separated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by preparative HPLC (C-18, AcN:H2O with 0.05% TFA)

Sources & evidence

ORD record
ord-3ccc1696dbf44e2fa57ff64076c0d1d0
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Reaction notes

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