Indomethacin → N-(2-{[1-(p-Chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl]acetoxy}ethyl)-3-pyridinecarboxamide

HRID 703728Notes

Reaction equation

HRID 703728 reaction equation
[CH3:1][C:2]1[N:10]([C:11]([C:13]2[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=2)=[O:12])[C:9]2[CH:8]=[CH:7][C:6]([O:20][CH3:21])=[CH:5][C:4]=2[C:3]=1[CH2:22][C:23]([OH:25])=[O:24].O[CH2:27][CH2:28][NH:29][C:30]([C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1)=[O:31].C1(N=C=NC2CCCCC2)CCCCC1.C(#N)C>CCOCC>[Cl:19][C:16]1[CH:15]=[CH:14][C:13]([C:11]([N:10]2[C:9]3[C:4](=[CH:5][C:6]([O:20][CH3:21])=[CH:7][CH:8]=3)[C:3]([CH2:22][C:23]([O:25][CH2:27][CH2:28][NH:29][C:30]([C:32]3[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=3)=[O:31])=[O:24])=[C:2]2[CH3:1])=[O:12])=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 3715IndomethacinHCID 6342AcetonitrileHCID 10868Dicyclohexylcarbodiimide2×HCID 72663N-(2-hydroxyethyl)nicotinamide

Product 1

HCID 15680016N-(2-{[1-(p-Chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl]acetoxy}ethyl)-3-pyridinecarboxamideYield 65.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A reaction of indomethacin (1.79 g, 5.00 mmol) and the product of Example 91 (0.830 g, 5.00 mmol) was carried out, using dicyclohexylcarbodiimide (1.10 g, 5.50 mmol) as the coupling agent and acetonitrile as the solvent. The first two reactants were dissolved completely and the solution was then cooled to 0° C. The dicyclohexylcarbodiimide was added and the mixture was stirred overnight. The reaction was allowed to continue for 48 hours. The precipitate (1.2 g) was removed by vacuum filtration. The solvent was removed from the filtrate under reduced pressure leaving an oily residue. The product was solidified by stirring with anhydrous ether. It was filtered, air-dried and recrystallized from ethanol/ether. The final product was vacuum filtered, washed with ether, and air dried. The product weighed 1.65 g, giving a 65.2% yield: mp 123°-125° C.

Workup

  1. dissolutionThe first two reactants were dissolved completely
  2. waitto continue for 48 hours
  3. customThe precipitate (1.2 g) was removed by vacuum filtration
  4. customThe solvent was removed from the filtrate under reduced pressure
  5. customleaving an oily residue
  6. filtrationIt was filtered
  7. customair-dried
  8. customrecrystallized from ethanol/ether
  9. filtrationfiltered
  10. washwashed with ether, and air
  11. customdried
  12. customgiving a 65.2% yield

Sources & evidence

ORD record
ord-bc4578d0c9ea4efe93227a30d901f2ed
Source dataset
uspto-grants-1991_01
Patent number
US04983586

Reaction notes

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