1,2-Dichloroethane → (E)-N-Hydroxy-3-(4-{(E)-3-[2-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylamide

HRID 885877ノート

反応式

HRID 885877 の反応式
Cl.Cl.C[N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[C:17](=[O:31])/[CH:18]=[CH:19]/[C:20]2[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28]([OH:30])=O)=[CH:22][CH:21]=2)C[CH2:5]1.C1C=CC2[N:40]([OH:41])N=NC=2C=1.[CH2:42](Cl)[CH2:43]Cl.NOC1CCCCO1>CN(C=O)C>[OH:41][NH:40][C:28](=[O:30])/[CH:27]=[CH:26]/[C:23]1[CH:24]=[CH:25][C:20](/[CH:19]=[CH:18]/[C:17]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH2:10][N:7]2[CH2:43][CH2:42][N:4]([CH3:5])[CH2:9][CH2:8]2)=[O:31])=[CH:21][CH:22]=1

参加物

6

反応物 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 44819902(E)-3-(4-{(E)-3-[2-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylic acid bis-hydrochloride

生成物 1

HCID 24756711(E)-N-Hydroxy-3-(4-{(E)-3-[2-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylamide収率 74.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of (E)-3-(4-{(E)-3-[2-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylic acid bis-hydrochloride (350 mg, 0.756 mmol), HOBT (204 mg, 1.51 mmol), EDC (288 mg, 1.51 mmol), TEA (0.210 ml, 1.51 mmol) and NH2OTHP (106 mg, 0.907 mmol) in DMF (8 ml) was stirred overnight at room temperature and then 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 extracts were 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 1 h. The hygroscopic precipitate was filtered and freeze dried to give 229 mg of (E)-N-Hydroxy-3-(4-{(E)-3-[2-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylamide as its bis-hydrochloride salt.

後処理

  1. custompartitioned between water and AcOEt
  2. customThe phases were separated
  3. extractionextracted with DCM
  4. dry with materialThe collected organic extracts were dried over Na2SO4
  5. customevaporated in vacuo
  6. customThe crude mixture was purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH 95:5:0.2)
  7. dissolutionthe resulting product was dissolved in DCM
  8. additiontreated with HCl/Et2O for 1 h
  9. filtrationThe hygroscopic precipitate was filtered
  10. customfreeze dried

出典と根拠

ORDレコード
ord-aa28a87a57304604b866382c8cd84f8d
出典データセット
uspto-grants-2012_08
特許番号
US08242175B2

反応ノート

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