1,2-Dichloroethane → HCID 86641370, compound

HRID 885865Notes

Reaction equation

HRID 885865 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16](=[O:30])/[CH:17]=[CH:18]/[C:19]3[CH:24]=[CH:23][C:22](/[CH:25]=[CH:26]/[C:27]([OH:29])=O)=[CH:21][CH:20]=3)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].C1C=CC2[N:39]([OH:40])N=NC=2C=1.C(Cl)C[Cl:43].NOC1CCCCO1>C1COCC1.CN(C=O)C>[ClH:43].[C:1]([N:4]1[CH2:5][CH2:6][N:7]([C:10]2[CH:11]=[CH:12][C:13]([C:16](=[O:30])/[CH:17]=[CH:18]/[C:19]3[CH:20]=[CH:21][C:22](/[CH:25]=[CH:26]/[C:27]([NH:39][OH:40])=[O:29])=[CH:23][CH:24]=3)=[CH:14][CH:15]=2)[CH2:8][CH2:9]1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 67049536HCID 67049536, compound

Product 1

HCID 86641370HCID 86641370, compoundYield 8.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

(E)-3-(4-{(E)-3-[4-(4-Acetyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylic acid (mixture of potassium salt and hydrochloric salt, 200 mg) was dissolved in THF (5 ml), DMF (5 ml) and TEA (0.126 ml, 0.908 mmol), then HOBT (122 mg, 0.908 mmol), EDC (173 mg, 0.908 mmol) and NH2OTHP (63.7 mg, 0.545 mmol) were added to the resulting solution. The mixture was stirred overnight at room temperature and then partitioned between water and AcOEt. The organic phase was dried over Na2SO4 and evaporated in vacuo. The crude mixture was purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH 96:4:0.2). The resulting product was dissolved in DCM and treated with HCl/Et2O for 1 h. The precipitate was filtered and crystallized from H2O/CH3CN/DMSO to give 20 mg of (E)-3-(4-{(E)-3-[4-(4-acetyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-phenyl)-N-hydroxy-acrylamide hydrochloride.

Workup

  1. custompartitioned between water and AcOEt
  2. dry with materialThe organic phase was dried over Na2SO4
  3. customevaporated in vacuo
  4. customThe crude mixture was purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH 96:4:0.2)
  5. dissolutionThe resulting product was dissolved in DCM
  6. additiontreated with HCl/Et2O for 1 h
  7. filtrationThe precipitate was filtered
  8. customcrystallized from H2O/CH3CN/DMSO

Sources & evidence

ORD record
ord-65b7a94a07814a079adff99d55fef662
Source dataset
uspto-grants-2012_08
Patent number
US08242175B2

Reaction notes

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