N-Methylcyclohexylamine → Cilostamide

HRID 1154948Notes

Reaction equation

HRID 1154948 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.C(N(CC)CC)C.S(Cl)(Cl)=O.[CH3:30][NH:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>C(Cl)(Cl)Cl>[CH3:30][N:31]([CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]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 8471TriethylamineHCID 24386Thionyl ChlorideHCID 128663424-((2-Oxo-1,2-dihydroquinolin-6-yl)oxy)butanoic acid

Product 1

HCID 2753Cilostamide

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

2.5 Grams of 6-(3-carboxypropoxy)carbostyril is suspended in 200 ml of chloroform, followed by addition of 1.5 ml of triethylamine, and then 1.2 g of thionyl chloride is added dropwise to the solution under agitation while maintaining the internal temperature at 0° to 20° C. After this addition, the mixture is agitated at the same temperature for 1 hour and then added dropwise with 2 ml of N-methylcyclohexylamine, followed by additional 3-hour agitation at room temperature. The reaction solution is washed well with a 5% aqueous K2CO3 solution, then further washed with water and diluted hydrochloric acid and then dried with anhydrous Na2SO4. After removing the solvent by distillation, the residue is refined by silica gel column chromatography (silica gel: Wakogel C-200; eluent: 10:1 chloroform/methanol (V/V)) and then recrystallized from chloroform-ethanol to obtain 0.4 g of 6-[3-(N-methyl-N-cyclohexylaminocarbonyl)propoxy]-carbostyril with melting point of 184.5°-186° C.

Workup

  1. temperaturewhile maintaining the internal temperature at 0° to 20° C
  2. additionAfter this addition
  3. waitfollowed by additional 3-hour agitation at room temperature
  4. washThe reaction solution is washed well with a 5% aqueous K2CO3 solution
  5. washfurther washed with water and diluted hydrochloric acid
  6. dry with materialdried with anhydrous Na2SO4
  7. customAfter removing the solvent
  8. distillationby distillation
  9. customrecrystallized from chloroform-ethanol

Sources & evidence

ORD record
ord-831eec8287e3463cbf94787c27680d39
Source dataset
uspto-grants-1981_11
Patent number
US04298739

Reaction notes

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