Dichloromethane → tert-Butyl 4-[(4-{[5-({[(4-methoxy-2,6-dimethylphenyl)sulfonyl](methyl)amino}methyl)-1,3,4-oxadiazol-2-yl]carbonyl}piperazin-1-yl)methyl]piperidine-1-carboxylate

HRID 469090Notes

Reaction equation

HRID 469090 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH3:28])[CH2:14][C:15]2[O:16][C:17]([C:20]([N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[O:21])=[N:18][N:19]=2)(=[O:12])=[O:11])=[C:5]([CH3:29])[CH:4]=1.[CH:30]([CH:32]1[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]1)=O.C(Cl)Cl.C(OC(=O)C)(=O)C>ClCCCl.CO>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH2:14][C:15]2[O:16][C:17]([C:20]([N:22]3[CH2:23][CH2:24][N:25]([CH2:30][CH:32]4[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:39])[CH2:34][CH2:33]4)[CH2:26][CH2:27]3)=[O:21])=[N:18][N:19]=2)[CH3:28])(=[O:11])=[O:12])=[C:5]([CH3:29])[CH:4]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 7918Acetic AnhydrideHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 583933044-Methoxy-N,2,6-trimethyl-N-{[5-(piperazin-1-ylcarbonyl)-1,3,4-oxadiazol-2-yl]methyl}benzenesulfonamide

Product 1

HCID 46175984tert-Butyl 4-[(4-{[5-({[(4-methoxy-2,6-dimethylphenyl)sulfonyl](methyl)amino}methyl)-1,3,4-oxadiazol-2-yl]carbonyl}piperazin-1-yl)methyl]piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Procedure

4-Methoxy-N,2,6-trimethyl-N-{[5-(piperazin-1-ylcarbonyl)-1,3,4-oxadiazol-2-yl]methyl}benzenesulfonamide (0.2 g, 0.44 mmol) and tert-butyl 4-formylpiperidine-1-carboxylate (0.14 g, 0.66 mmol) were dissolved in DCE (4 mL) and a few 4 Å molecular sieves added. The reaction was stirred for 30 min at ambient temperature prior to addition of STAB (0.28 g, 1.3 mmol). The reaction was stirred for 18 h, diluted with MeOH (0.5 mL) and concentrated in vacuo. The residue was redissolved in DCM (5 mL) and filtered through Celite, washing with DCM. The DCM solution was treated with acetic anhydride (0.1 mL, 1.0 mmol) and stirred for 30 min at ambient temperature. The solvent was removed in vacuo and the residue redissolved in MeOH (2 mL) and the solution absorbed on to a 2 g SCX cartridge. The sorbent was washed with MeOH (10 mL) and the product eluted with 7 N NH3 in MeOH (10 mL). The solvent was removed in vacuo to afford the title compound.

Workup

  1. additiona few 4 Å molecular sieves added
  2. additionto addition of STAB (0.28 g, 1.3 mmol)
  3. stirringThe reaction was stirred for 18 h
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was redissolved in DCM (5 mL)
  6. filtrationfiltered through Celite
  7. washwashing with DCM
  8. stirringstirred for 30 min at ambient temperature
  9. customThe solvent was removed in vacuo
  10. dissolutionthe residue redissolved in MeOH (2 mL)
  11. customthe solution absorbed on to a 2 g SCX cartridge
  12. washThe sorbent was washed with MeOH (10 mL)
  13. washthe product eluted with 7 N NH3 in MeOH (10 mL)
  14. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-64b1f93acff8485a91c06115aa95b1d9
Source dataset
uspto-grants-2014_01
Patent number
US08623859B2

Reaction notes

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