1,2-Dichloroethane → HCID 24756976, compound

HRID 885891Notes

Reaction equation

HRID 885891 reaction equation
[K].C(OC([N:9]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22](=[O:36])/[CH:23]=[CH:24]/[C:25]3[CH:26]=[N:27][C:28](/[CH:31]=[CH:32]/[C:33]([OH:35])=O)=[CH:29][CH:30]=3)=[CH:18][CH:17]=2)[CH2:11][CH2:10]1)=O)(C)(C)C.C1C=CC2[N:45]([OH:46])N=NC=2C=1.C(Cl)CCl.NOC1CCCCO1>CN(C=O)C.C(Cl)Cl>[OH:46][NH:45][C:33](=[O:35])/[CH:32]=[CH:31]/[C:28]1[CH:29]=[CH:30][C:25](/[CH:24]=[CH:23]/[C:22](=[O:36])[C:19]2[CH:20]=[CH:21][C:16]([CH2:15][N:12]3[CH2:13][CH2:14][NH:9][CH2:10][CH2:11]3)=[CH:17][CH:18]=2)=[CH:26][N:27]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 67049462HCID 67049462, compound

Product 1

HCID 24756976HCID 24756976, compoundYield 21.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 4-(4-{(E)-3-[6-((E)-2-carboxy-vinyl)-pyridin-3-yl]-acryloyl}-benzyl)-piperazine-1-carboxylic acid tert-butyl ester potassium salt (250 mg, 0.48 mmol), HOBT (130 mg, 0.96 mmol), EDC (184 mg, 0.96 mmol), TEA (0.134 ml, 0.96 mmol) and NH2OTHP (84 mg, 0.72 mmol) in DMF (4 ml) and DCM (4 ml) was stirred at room temperature for 5 h. The solution was diluted with DCM and washed with water and brine. The organic phase was dried over Na2SO4 and evaporated in vacuo. The crude mixture was purified by column chromatography (eluent: DCM/MeOH/NH4OH 95:5:0.1) and the resulting product was dissolved in DCM and treated with HCl/Et2O for 4 h. The resulting precipitate was filtered and purified by preparative LC-MS to give 40 mg of (E)-N-hydroxy-3-{5-[(E)-3-oxo-3-(4-piperazin-1-ylmethyl-phenyl)-propenyl]-pyridin-2-yl}-acrylamide as its formate salt.

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic phase was dried over Na2SO4
  3. customevaporated in vacuo
  4. customThe crude mixture was purified by column chromatography (eluent: DCM/MeOH/NH4OH 95:5:0.1)
  5. dissolutionthe resulting product was dissolved in DCM
  6. additiontreated with HCl/Et2O for 4 h
  7. filtrationThe resulting precipitate was filtered
  8. custompurified by preparative LC-MS

Sources & evidence

ORD record
ord-720f23042e534d8b925567c8ac228c98
Source dataset
uspto-grants-2012_08
Patent number
US08242175B2

Reaction notes

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