1,2-Dichloroethane → HCID 24756885, compound

HRID 885878Notes

Reaction equation

HRID 885878 reaction equation
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15](=[O:29])/[CH:16]=[CH:17]/[C:18]2[CH:19]=[CH:20][C:21](/[CH:24]=[CH:25]/[C:26]([OH:28])=O)=[N:22][CH:23]=2)[CH2:5][CH2:4]1.C1C=CC2[N:38]([OH:39])N=NC=2C=1.C(Cl)CCl.NOC1CCCCO1>CN(C=O)C>[OH:39][NH:38][C:26](=[O:28])/[CH:25]=[CH:24]/[C:21]1[CH:20]=[CH:19][C:18](/[CH:17]=[CH:16]/[C:15]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:6]2[CH2:5][CH2:4][N:3]([CH3:2])[CH2:8][CH2:7]2)=[O:29])=[CH:23][N:22]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 67049700HCID 67049700, compound

Product 1

HCID 24756885HCID 24756885, compoundYield 6.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(E)-3-(5-{(E)-3-[2-(4-Methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acid hydrochloride (crude mixture from Step A, 400 mg) was suspended in DMF (10 ml). HOBT (240 mg, 1.78 mmol), EDC (340 mg, 1.78 mmol), TEA (0.371 ml, 2.67 mmol) and NH2OTHP (125 mg, 1.06 mmol) were added to the resulting slurry. The mixture was stirred overnight at room temperature and then partitioned between water and AcOEt. The organic phase was washed with water, dried over Na2SO4 and evaporated in vacuo. The crude reaction mixture was purified by column chromatography (DCM/MeOH/NH4OH 95:5:0.2). The collected fractions were evaporated and the resulting product was dissolved in DCM and treated with HCl/Et2O for 1 h. The precipitate was filtered off and purified by preparative LC-MS to give 23.7 mg of (E)-N-hydroxy-3-(5-{(E)-3-[2-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylamide as its trifluoroacetate salt.

Workup

  1. custompartitioned between water and AcOEt
  2. washThe organic phase was washed with water
  3. dry with materialdried over Na2SO4
  4. customevaporated in vacuo
  5. customThe crude reaction mixture
  6. customwas purified by column chromatography (DCM/MeOH/NH4OH 95:5:0.2)
  7. customThe collected fractions were evaporated
  8. dissolutionthe resulting product was dissolved in DCM
  9. additiontreated with HCl/Et2O for 1 h
  10. filtrationThe precipitate was filtered off
  11. custompurified by preparative LC-MS

Sources & evidence

ORD record
ord-0f529fa0a8fd4017b36f5af2571d8d29
Source dataset
uspto-grants-2012_08
Patent number
US08242175B2

Reaction notes

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