HCID 178522861, compound → N-(4-Chlorobenzyl)-6-[(1E)-3-hydroxy-1-propenyl]-4-hydroxy-3-quinolinecarboxamide

HRID 2289991Notes

Reaction equation

HRID 2289991 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16]([C:21]#[C:22][CH2:23][OH:24])=[CH:15][CH:14]=3)=[O:9])=[CH:4][CH:3]=1>[Pd].C(Cl)Cl.CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[C:16](/[CH:21]=[CH:22]\[CH2:23][OH:24])[CH:17]=3)[NH:12][CH:11]=2)=[O:9])=[CH:25][CH:26]=1.[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[C:16](/[CH:21]=[CH:22]/[CH2:23][OH:24])[CH:17]=3)[NH:12][CH:11]=2)=[O:9])=[CH:25][CH:26]=1

Participants

5

Reactant 1

HCID 178522861HCID 178522861, compound

Product 2

HCID 21192519N-(4-Chlorobenzyl)-6-[(1E)-3-hydroxy-1-propenyl]-4-hydroxy-3-quinolinecarboxamideHCID 54392005N-(4-chlorobenzyl)-6-[(1Z)-3-hydroxy-1-propenyl]-4-hydroxy-3-quinolinecarboxamide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 21226129Dichloromethane methanolSolvent

Procedure

A mixture of N-(4-chlorobenzyl)-4-hydroxy-6-(3-hydroxy-1-propynyl)-3-quinolinecarboxamide from Example 134 (5.48 g) and Pd/C (10%, 0.55 g) in 3:1 CH2Cl2 /MeOH (150 mL) are placed on a Parr hydrogenator under 50 psi of H2 and shaken for 4 h. Another 0.30 g of Pd/C was added, and the resulting mixture was shaken for 2 h. The reaction mixture is then filtered through Celite, 0.55 g of fresh catalyst is added, and the resulting mixture is shaken under H2 for 3 h. The reaction mixture is then filtered through Celite and concentrated in vacuo. Trituration from CHCl3 /MeOH affords a solid which is purified by HPLC chromatography on a 0.46×25 cm Chiralcel OD-H column eluting with EtOH at a rate of 0.3 mL/min to give 0.383 g of N-[(4-chlorophenyl)methyl]-1,4-dihydro-6-[(1Z)-3-hydroxy-1-propenyl]-4-oxo-3-quinolinecarboxamide (cis title compound), and 0.492 g of N-[(4-chlorophenyl)methyl]-1,4-dihydro-6-[(1E)-3-hydroxy-1-propeny]-4-oxo-3-quinolinecarboxamide (trans title compound). Crystallization of the cis isomer from ethyl acetate gave 0.29 g of the title cis compound as a solid. Crystallization of the trans isomer from CH2Cl2 /MeOH gave 0.289 g of the title trans compound as a solid.

Workup

  1. stirringthe resulting mixture was shaken for 2 h
  2. filtrationThe reaction mixture is then filtered through Celite, 0.55 g of fresh catalyst
  3. additionis added
  4. stirringthe resulting mixture is shaken under H2 for 3 h
  5. filtrationThe reaction mixture is then filtered through Celite
  6. concentrationconcentrated in vacuo
  7. customTrituration from CHCl3 /MeOH affords a solid which
  8. customis purified by HPLC chromatography on a 0.46×25 cm Chiralcel OD-H column
  9. washeluting with EtOH at a rate of 0.3 mL/min

Sources & evidence

ORD record
ord-e04dce54bcfb44be8d28716294e8c8dd
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

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