1,2-Dichloroethane → HCID 16750431, compound

HRID 885886Notes

Reaction equation

HRID 885886 reaction equation
Cl.C(OC([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:35])/[CH:22]=[CH:23]/[C:24]3[CH:25]=[N:26][C:27](/[CH:30]=[CH:31]/[C:32]([OH:34])=O)=[CH:28][CH:29]=3)=[CH:17][CH:16]=2)[CH2:11][CH2:10]1)=O)(C)(C)C.C(Cl)CCl.C1C=CC2[N:48]([OH:49])N=NC=2C=1.NOC1CCCCO1>CN(C=O)C.C1COCC1>[OH:49][NH:48][C:32](=[O:34])/[CH:31]=[CH:30]/[C:27]1[CH:28]=[CH:29][C:24](/[CH:23]=[CH:22]/[C:21](=[O:35])[C:18]2[CH:17]=[CH:16][C:15]([N:12]3[CH2:11][CH2:10][NH:9][CH2:14][CH2:13]3)=[CH:20][CH:19]=2)=[CH:25][N:26]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 670493874-(4-{(E)-3-[6-((E)-2-carboxy-vinyl)-pyridin-3-yl]-acryloyl}-phenyl)-piperazine-1-carboxylic acid tert-butyl ester hydrochloride

Product 1

HCID 16750431HCID 16750431, compoundYield 38.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-(4-{(E)-3-[6-((E)-2-carboxy-vinyl)-pyridin-3-yl]-acryloyl}-phenyl)-piperazine-1-carboxylic acid tert-butyl ester hydrochloride (184 mg, 0.363 mmol) was dissolved in DMF (5 ml), THF (5 ml) and TEA (0.190 ml, 1.47 mmol). Then EDC (140 mg, 0.736 mmol), HOBT (99 mg, 0.736 mmol) and NH2OTHP (51.6 mg, 0.441 mmol) were added to the resulting solution. The mixture was stirred at room temperature overnight and then partitioned between water and AcOEt. The organic phase was dried over Na2SO4 and evaporated in vacuo. The crude reaction mixture was purified by column chromatography (eluent: DCM/MeOH/NH4OH 98:2:0.2) and the resulting compound was dissolved in DCM and treated with HCl/Et2O for 1 h. The precipitate was filtered off and washed with DCM. The hygroscopic powder was dissolved in water and freeze dried to give 53 mg of (E)-N-hydroxy-3-{5-[(E)-3-oxo-3-(4-piperazin-1-yl-phenyl)-propenyl]-pyridin-2-yl}-acrylamide as its bis-hydrochloride salt.

Workup

  1. custompartitioned between water and AcOEt
  2. dry with materialThe organic phase was dried over Na2SO4
  3. customevaporated in vacuo
  4. customThe crude reaction mixture
  5. customwas purified by column chromatography (eluent: DCM/MeOH/NH4OH 98:2:0.2)
  6. dissolutionthe resulting compound was dissolved in DCM
  7. additiontreated with HCl/Et2O for 1 h
  8. filtrationThe precipitate was filtered off
  9. washwashed with DCM
  10. dissolutionThe hygroscopic powder was dissolved in water
  11. customfreeze dried

Sources & evidence

ORD record
ord-4c3df464c61b4c12bbcc43491b131b26
Source dataset
uspto-grants-2012_08
Patent number
US08242175B2

Reaction notes

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