Dimethylformamide → 2,6-Dichloro-N-{[(1S,3S)-1-hydroxy-3-methylcyclohexyl]methyl}quinoline-5-carboxamide

HRID 2424831Notes

Reaction equation

HRID 2424831 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([C:12]([OH:14])=O)=[C:7]([Cl:15])[CH:6]=[CH:5][C:4]=2[N:3]=1.[C:16](Cl)(=[O:20])[C:17](Cl)=O.C[N:23]([CH3:26])C=O>ClCCl>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([C:12]([NH:23][CH2:26][C@:16]3([OH:20])[CH2:17][CH2:6][CH2:7][C@H:8]([CH3:12])[CH2:9]3)=[O:14])=[C:7]([Cl:15])[CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 577339932,6-Dichloroquinoline-5-carboxylic acid

Product 1

HCID 866233642,6-Dichloro-N-{[(1S,3S)-1-hydroxy-3-methylcyclohexyl]methyl}quinoline-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of 2,6-dichloro-quinoline-5-carboxylic acid (2.40 g) (WO2004/106305, Example 76, step b) in dichloromethane (100 ml) was added oxalyl chloride (3.15 g, 2.16 ml) and a drop of N,N-dimethylformamide. The reaction was stirred at room temperature for 2 hours before the volatiles were removed in vacuo and the residue diluted in dichloromethane (100 ml). To this solution were added (1S,3S)-1-(aminomethyl)-3-methylcyclohexanol.HCl (1.78 g) and diisopropylethylamine (6.70 ml) and the reaction stirred for 20 hours before washing with water. The organic layer was dried (MgSO4), filtered and the volatiles were evaporated to provide a crude solid. The material was recrystallised from toluene to provide the subtitle compound as a beige solid (2.5 g).

Workup

  1. customwere removed in vacuo
  2. additionthe residue diluted in dichloromethane (100 ml)
  3. additionTo this solution were added (1S,3S)-1-(aminomethyl)-3-methylcyclohexanol
  4. stirringHCl (1.78 g) and diisopropylethylamine (6.70 ml) and the reaction stirred for 20 hours
  5. washbefore washing with water
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. customthe volatiles were evaporated
  9. customto provide a crude solid
  10. customThe material was recrystallised from toluene

Sources & evidence

ORD record
ord-77dacb9cbe164c9d95ac239cfa457e35
Source dataset
uspto-grants-2011_06
Patent number
US07964616B2

Reaction notes

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