1,2-Dichloroethane → HCID 86641374, compound

HRID 885888Notes

Reaction equation

HRID 885888 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([N:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]2)=[C:7]([C:9](=[O:23])/[CH:10]=[CH:11]/[C:12]2[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20](O)=[O:21])=[CH:14][CH:13]=2)[CH:8]=1.C1C=CC2[N:39]([OH:40])N=NC=2C=1.C(Cl)CCl.NOC1CCCCO1>C(Cl)Cl>[ClH:2].[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([N:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]2)=[C:7]([C:9](=[O:23])/[CH:10]=[CH:11]/[C:12]2[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20]([NH:39][OH:40])=[O:21])=[CH:14][CH:13]=2)[CH:8]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 67049719HCID 67049719, compound

Product 1

HCID 86641374HCID 86641374, compoundYield 47.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (E)-3-(4-{(E)-3-[5-chloro-2-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylic acid hydrochloride (250 mg, 0.56 mmol), HOBT (139 mg, 1.03 mmol), EDC (196 mg, 1.03 mmol), TEA (0.568 ml, 4.08 mmol) and NH2OTHP (89 mg, 0.765 mmol) in DCM (5 ml) was stirred overnight at room temperature. The solvent was evaporated and the residue was partitioned between water and AcOEt. The phases were separated and the aqueous layer was brought to basic conditions with NH4OH and extracted with DCM. The collected organic extract were dried over Na2SO4 and evaporated in vacuo. The crude mixture was purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH 97:3:0.1) and the resulting product was dissolved in DCM and treated with HCl/Et2O for 2.5 h. The precipitate was filtered and triturated with isopropanol and di-isopropylether to give 61 mg of (E)-3-(4-{(E)-3-[5-chloro-2-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-phenyl)-N-hydroxy-acrylamide hydrochloride.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was partitioned between water and AcOEt
  3. customThe phases were separated
  4. extractionextracted with DCM
  5. extractionThe collected organic extract
  6. dry with materialwere dried over Na2SO4
  7. customevaporated in vacuo
  8. customThe crude mixture was purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH 97:3:0.1)
  9. dissolutionthe resulting product was dissolved in DCM
  10. additiontreated with HCl/Et2O for 2.5 h
  11. filtrationThe precipitate was filtered
  12. customtriturated with isopropanol and di-isopropylether

Sources & evidence

ORD record
ord-408debdda7d64bee931d226eca479acb
Source dataset
uspto-grants-2012_08
Patent number
US08242175B2

Reaction notes

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