N-Methylcyclohexylamine → Cilostamide

HRID 1154945Notes

Reaction equation

HRID 1154945 reaction equation
[C:1]([CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13](=[O:18])[CH:12]=[CH:11]2)([OH:3])=O.[CH3:19][NH:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.O1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[CH3:19][N:20]([CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)[C:1]([CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13](=[O:18])[CH:12]=[CH:11]2)=[O:3]

Participants

6

Reactant 4

HCID 7514N-MethylcyclohexylamineHCID 10868DicyclohexylcarbodiimideHCID 312751,4-DioxaneHCID 128663424-((2-Oxo-1,2-dihydroquinolin-6-yl)oxy)butanoic acid

Product 1

HCID 2753Cilostamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2.5 Grams of 6-(3-carboxy)propoxycarbostyril and 1.2 g of N-methylcyclohexylamine are added to a mixed solvent of 20 ml of dioxane and 20 ml of methylene chloride, and to this mixture is added dropwise a solution of 2.1 g of N,N'-dicyclohexylcarbodiimide in 5 ml of methylene chloride maintained at 10°-20° C. under external ice cooling and agitation, followed by additional 3.5-hour agitation at the same temperature. The precipitated crystals are filtered out and the filtrate is concentrated under reduced pressure and evaporated to dryness. The obtained residue is dissolved in 100 ml of methylene chloride and the organic layer is washed with a 5% aqueous solution of hydrochloric acid, a 5% aqueous solution of sodium carbonate and water in that order and then dried with anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue is recrystallized from chloroform-ethanol to obtain 1.9 g of 6-[3-(N-methyl-N-cyclohexylaminocarbonyl)propoxy]-carbostyril in the form of colorless needle-like crystals with melting point of 184.5°- 186° C.

Workup

  1. temperaturemaintained at 10°-20° C. under external ice cooling
  2. waitagitation, followed by additional 3.5-hour
  3. filtrationThe precipitated crystals are filtered out
  4. concentrationthe filtrate is concentrated under reduced pressure
  5. customevaporated to dryness
  6. dissolutionThe obtained residue is dissolved in 100 ml of methylene chloride
  7. washthe organic layer is washed with a 5% aqueous solution of hydrochloric acid
  8. dry with materiala 5% aqueous solution of sodium carbonate and water in that order and then dried with anhydrous sodium sulfate
  9. distillationAfter distilling off the solvent under reduced pressure
  10. customthe residue is recrystallized from chloroform-ethanol

Sources & evidence

ORD record
ord-188ceb7613104159bbd80b33cd70dca1
Source dataset
uspto-grants-1981_11
Patent number
US04298739

Reaction notes

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