Water → HCID 16073841, compound

HRID 1067973Notes

Reaction equation

HRID 1067973 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.C([O-])([O-])=O.[K+].[K+].Br[CH2:34][CH2:35]Br.O>CN(C=O)C>[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]([C:21]#[C:22][CH2:23][OH:24])[CH:17]=3)[N:12]([CH:34]=[CH2:35])[CH:11]=2)=[O:9])=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 962WaterHCID 78391,2-DibromoethaneHCID 11430Potassium CarbonateHCID 178522861HCID 178522861, compound

Product 1

HCID 16073841HCID 16073841, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of N-(4-chlorobenzyl)-4-hydroxy-6-(3-hydroxy-1-propynyl)-3-quinolinecarboxamide from Preparation No. 5 (1.83 g) is dissolved in DMF (25 mL), and K2CO3 (1.38 g) and 1,2-dibromoethane (4.3 mL) are added. The reaction mixture is heated to 90° C. for 2 h. Water is added and the mixture is extracted with ethyl acetate and then chloroform. The combined organic layers are concentrated in vacuo to give 2.5 g of a dark oil. Column chromatography (elution with 1-3% MeOH/CHCl3) gave 0.378 g of 1-(1-bromoethyl)-N-(4-chlorobenzyl)-6-(3-hydroxy-1-propynyl)-4-oxo-1,4-dihydro-3-quinolinecarboxamide as a solid which is used without further purification. 1-(1-bromoethyl)-N-(4-chlorobenzyl)-6-(3-hydroxy-1-propynyl)-4-oxo-1,4-dihydro-3-quinolinecarboxamide (0.347 g) is suspended in 1:1 THF/CH3CN (15 mL) and sodium carbonate (0.16 g) and ethylamine (0.4 mL) are added and the mixture is refluxed for 16 h. An additional amount of ethylamine (0.80 mL) is added and the mixture is refluxed for 16 h. An additional amount of ethylamine (0.80 mL) and DMF (5 mL) is added and the mixture is heated at 100° C. for 6 h, and then held at room temperature for 48 h. Potassium carbonate (0.193 g) is added and the mixture is heated at 100° C. for 3 h. The mixture is concentrated in vacuo and partitioned between ethyl acetate and water. The organic layer is concentrated in vacuo to give 0.60 g of an oil. Column chromatography (elution with 1-5% MeOH/CHCl3) gave 0.118 g of the title compound as a solid.

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. concentrationThe combined organic layers are concentrated in vacuo

Sources & evidence

ORD record
ord-9a46658374d14ccf8835d36bbfb6b2c9
Source dataset
uspto-grants-2001_06
Patent number
US06248739B1

Reaction notes

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