tert-Butyl piperazine-1-carboxylate → HCID 24757863, compound

HRID 885873Notes

Reaction equation

HRID 885873 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)(OC(C)(C)C)=O.O1CCCCC1[O:20][NH:21][C:22](/[CH:24]=[CH:25]/[C:26]1[CH:31]=[CH:30][C:29](/[CH:32]=[CH:33]/[C:34]([C:36]2[CH:47]=[CH:46][C:39](COS(C)(=O)=O)=[CH:38][CH:37]=2)=[O:35])=[CH:28][CH:27]=1)=[O:23]>CN(C=O)C.C(Cl)Cl.O>[OH:20][NH:21][C:22](=[O:23])/[CH:24]=[CH:25]/[C:26]1[CH:31]=[CH:30][C:29](/[CH:32]=[CH:33]/[C:34](=[O:35])[C:36]2[CH:47]=[CH:46][C:39]([CH2:1][N:8]3[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]3)=[CH:38][CH:37]=2)=[CH:28][CH:27]=1

Participants

6

Reactant 2

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 59312563HCID 59312563, compound

Product 1

HCID 24757863HCID 24757863, compoundYield 52.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

N-Boc-piperazine (46 mg, 0.246 mmol) was added to a stirred mixture of methanesulfonic acid 4-((E)-3-{4-[(E)-2-(tetrahydro-pyran-2-yloxycarbamoyl)-vinyl]-phenyl}-acryloyl)-benzyl ester (prepared as described in Preparation 5, 100 mg, 0.206 mmol) and TEA (0.057 ml, 0.412 mmol) in DMF (1 ml) and DCM (1 ml). The resulting solution was stirred at room temperature for 1 h. The mixture was diluted with water and extracted with AcOEt. The organic phase was washed with water, dried over Na2SO4 and evaporated in vacuo. The crude mixture was purified by column chromatography (eluent: DCM/MeOH/NH4OH 99:1:0.2). The resulting product was dissolved in DCM and treated with HCl/Et2O for 4 h. The precipitate was filtered off and rinsed with DCM to give 42.6 mg of (E)-N-hydroxy-3-{4-[(E)-3-oxo-3-(4-piperazin-1-ylmethyl-phenyl)-propenyl]-phenyl}-acrylamide as its bis-hydrochloride salt.

Workup

  1. extractionextracted with AcOEt
  2. washThe organic phase was washed with water
  3. dry with materialdried over Na2SO4
  4. customevaporated in vacuo
  5. customThe crude mixture was purified by column chromatography (eluent: DCM/MeOH/NH4OH 99:1:0.2)
  6. dissolutionThe resulting product was dissolved in DCM
  7. additiontreated with HCl/Et2O for 4 h
  8. filtrationThe precipitate was filtered off
  9. washrinsed with DCM

Sources & evidence

ORD record
ord-604da997449f46dd99ee43e176cf923e
Source dataset
uspto-grants-2012_08
Patent number
US08242175B2

Reaction notes

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