1,2-Dichloroethane → HCID 86641376, compound

HRID 885896Notes

Reaction equation

HRID 885896 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:4][C:3]=1[C:15](=[O:29])/[CH:16]=[CH:17]/[C:18]1[CH:23]=[CH:22][C:21](/[CH:24]=[CH:25]/[C:26]([OH:28])=O)=[CH:20][CH:19]=1.C1C=CC2[N:38]([OH:39])N=NC=2C=1.C(Cl)CCl.NOC1CCCCO1>CN(C=O)C.O>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:9][CH2:10][N:11]([CH3:14])[CH2:12][CH2:13]2)=[CH:4][C:3]=1[C:15](=[O:29])/[CH:16]=[CH:17]/[C:18]1[CH:19]=[CH:20][C:21](/[CH:24]=[CH:25]/[C:26]([NH:38][OH:39])=[O:28])=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 67050170HCID 67050170, compound2×

Product 1

HCID 86641376HCID 86641376, compoundYield 107.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (E)-3-(4-{(E)-3-[2-chloro-5-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylic acid (compound from STEP A, 205 mg), HOBT (134 mg, 0.99 mmol), EDC (190 mg, 0.99 mmol), TEA (0.138 ml, 0.99 mmol) and NH2OTHP (70 mg, 0.60 mmol) in DMF (10 ml) was stirred at room temperature overnight. The reaction mixture was diluted with water and extracted with AcOEt twice. The organic phases were washed with water, brine and then dried over Na2SO4 and evaporated in vacuo. The crude mixture was purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH 95:5:0.2) and the resulting product was dissolved in DCM and treated with HCl/Et2O for 3 h. The precipitate was filtered and rinsed with DCM and Et2O to give 124 mg of (E)-3-(4-{(E)-3-[2-chloro-5-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-phenyl)-N-hydroxy-acrylamide hydrochloride.

Workup

  1. extractionextracted with AcOEt twice
  2. washThe organic phases were washed with water, brine
  3. dry with materialdried over Na2SO4
  4. customevaporated in vacuo
  5. customThe crude mixture was purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH 95:5:0.2)
  6. dissolutionthe resulting product was dissolved in DCM
  7. additiontreated with HCl/Et2O for 3 h
  8. filtrationThe precipitate was filtered
  9. washrinsed with DCM and Et2O

Sources & evidence

ORD record
ord-7e4fe9d5b5ea4d9d996cd29028eae2ad
Source dataset
uspto-grants-2012_08
Patent number
US08242175B2

Reaction notes

Loading…