Sulfuric acid magnesium salt (1:1) → 2-(3,5-dimethylphenyl)-3-[2-[4-(pyridin-4-yl)butylamino]-ethyl]-1H-indole-5-carboxylic acid ethyl ester

HRID 1956515Notes

Reaction equation

HRID 1956515 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]([C:15]1[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([CH3:22])[CH:16]=1)=[C:9]2[CH2:23][CH2:24][NH2:25])=[O:5])[CH3:2].[N:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][CH2:34][CH:35]=O)=[CH:28][CH:27]=1.S([O-])([O-])(=O)=O.[Mg+2].[Na]>>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]([C:15]1[CH:16]=[C:17]([CH3:22])[CH:18]=[C:19]([CH3:21])[CH:20]=1)=[C:9]2[CH2:23][CH2:24][NH:25][CH2:35][CH2:34][CH2:33][CH2:32][C:29]1[CH:30]=[CH:31][N:26]=[CH:27][CH:28]=1)=[O:5])[CH3:2]

Participants

5

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 5360545SodiumHCID 114464344-Pyridin-4-ylbutanalHCID 538575973-(2-aminoethyl)-2-(3,5-dimethylphenyl)-1H-indole-5-carboxylic acid ethyl ester

Product 1

HCID 543970972-(3,5-dimethylphenyl)-3-[2-[4-(pyridin-4-yl)butylamino]-ethyl]-1H-indole-5-carboxylic acid ethyl esterYield 50.3%

Conditions

Temperature
-10 °C

Procedure

To a dry flask were added 5.0 g (14.9 mmol) of 3-(2-aminoethyl)-2-(3,5-dimethylphenyl)-1H-indole-5-carboxylic acid ethyl ester, 1.98 g (13.5 mmol) of 4-(pyridin-4-yl)butyraldehyde (diluted with 0.5 mL of CDCl3), 8.12 g (67.7 mmol) of anhydrous magnesium sulfate, and a magnetic stirring bar. The flask was purged with nitrogen, cooled to -10° C., and stirred as 11.5 mL of dry CDCl3 was introduced gradually by syringe. The mixture was stirred under nitrogen for about 20 minutes. Next, the septum was removed, and 670 mg (17.6 mmol) of sodium borohyrdide was added rapidly. The septum was immediately replaced, and the system was again purged with nitrogen. The mixture was stirred under nitrogen at about -5° C. as 10 mL of dry methanol was added gradually by syringe. After a few minutes at this temperature, the reaction was removed from the cooling bath and partitioned between 80 mL of ethyl acetate and 100 mL of water. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (elution with a gradient of 4-9% methanol in methylene chloride; repeated using 5-15% methanol in methylene chloride) to give the title compound (3.19 g). 500 MHz 1H NMR (CDCl3) was consistent with the assigned structure. Mass spectrum (PB--NH3 /CI): m/e=470.4 (M+H). An additional 1.91 g of less pure material was also isolated.

Workup

  1. customThe flask was purged with nitrogen
  2. additionwas introduced gradually by syringe
  3. stirringThe mixture was stirred under nitrogen for about 20 minutes
  4. customNext, the septum was removed
  5. customthe system was again purged with nitrogen
  6. stirringThe mixture was stirred under nitrogen at about -5° C. as 10 mL of dry methanol
  7. additionwas added gradually by syringe
  8. waitAfter a few minutes at this temperature
  9. customthe reaction was removed from the cooling bath
  10. custompartitioned between 80 mL of ethyl acetate and 100 mL of water
  11. dry with materialThe organic layer was dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash chromatography on silica gel (
  15. washelution with a gradient of 4-9% methanol in methylene chloride

Sources & evidence

ORD record
ord-7c793f6c52064b71ac3fe218c6948357
Source dataset
uspto-grants-1998_07
Patent number
US05780437

Reaction notes

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