Sodium Dithionite → 1-Methyl-3-[N-(2-{[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl]acetoxy}ethyl)carbamoyl]-1,4-dihydropyridine

HRID 1494189Notes

Reaction equation

HRID 1494189 reaction equation
[I-].[CH3:2][N+:3]1[CH:8]=[CH:7][CH:6]=[C:5]([C:9](=[O:38])[NH:10][CH2:11][CH2:12][O:13][C:14](=[O:37])[CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([O:25][CH3:26])[CH:23]=3)[N:18]([C:27](=[O:35])[C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[C:17]=2[CH3:36])[CH:4]=1.C(=O)(O)[O-].[Na+].S(S([O-])=O)([O-])=O.[Na+].[Na+]>O.C(#N)C>[CH3:2][N:3]1[CH:8]=[CH:7][CH2:6][C:5]([C:9](=[O:38])[NH:10][CH2:11][CH2:12][O:13][C:14](=[O:37])[CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([O:25][CH3:26])[CH:23]=3)[N:18]([C:27](=[O:35])[C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[C:17]=2[CH3:36])=[CH:4]1

Participants

5

Reactant 3

HCID 24489Sodium DithioniteHCID 516892Sodium BicarbonateHCID 156800191-Methyl-3-[N-(2-{[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl]acetoxy}ethyl)carbamoyl]pyridinium iodide

Product 1

HCID 156800221-Methyl-3-[N-(2-{[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl]acetoxy}ethyl)carbamoyl]-1,4-dihydropyridineYield 82%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

The indomethacin quaternary salt prepared in Example 95 (140 mg, 0.22 mmol), was dissolved in a minimum amount of water:acetonitrile (8:2). The water had been bubbled with nitrogen for 20 minutes prior to its use. Sodium bicarbonate (91 mg, 1.1 mmol) and sodium dithionite (110 mg, 0.65 mmol) were added to the solution while stirring at 0° C. The solution was then allowed to warm to room temperature. The reaction was continued for about 1 hour. Some of the product had precipitated during the reaction. This was dissolved in ethyl ether. The water layer was extracted several times with ether until no more yellow color transferred to the organic layer. The ether portions were combined and dried with magnesium sulfate, filtered and the ether was removed under reduced pressure. The resulting oil was dissolved in acetone and the solvent was removed (2×10 mL) under reduced pressure to form a dry foam. The final product weighed 92 mg. The yield was 82%; mp 60°-65° C. The product had the formula: ##STR126## as confirmed by UV, NMR and elemental analyses.

Workup

  1. customThe water had been bubbled with nitrogen for 20 minutes
  2. temperatureto warm to room temperature
  3. customSome of the product had precipitated during the reaction
  4. dissolutionThis was dissolved in ethyl ether
  5. extractionThe water layer was extracted several times with ether until no more yellow color
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. customthe ether was removed under reduced pressure
  9. dissolutionThe resulting oil was dissolved in acetone
  10. customthe solvent was removed (2×10 mL) under reduced pressure
  11. customto form a dry foam

Sources & evidence

ORD record
ord-bccc822d62314e10b4cfc09cd18b27e6
Source dataset
uspto-grants-1991_06
Patent number
US05024998

Reaction notes

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