Triethylamine → HCID 22611567, compound

HRID 726074Notes

Reaction equation

HRID 726074 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1.[C:18]1([C:28]([Cl:30])=[O:29])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[CH:20][CH:19]=1.C(N(CC)CC)C>O1CCCC1>[ClH:30].[C:18]1([C:28]([NH:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[C:5]3[CH:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)=[O:29])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 701461-Naphthalenecarbonyl chloride2×HCID 118312203-(1-Methylpiperidin-4-yl)-1h-indol-5-amine

Product 1

HCID 22611567HCID 22611567, compoundYield 58.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 1.2 gm (5.2 mMol) 5-amino-3-(1-methylpiperidin-4-yl)-1H-indole in 50 mL tetrahydrofuran were added 0.946 mL (6.3 mMol) 1-naphthoyl chloride dropwise. After 18 hours the reaction mixture was filtered. The recovered filtrate was dissolved in 10 mL dimethylformamide to which were added 1.5 mL (10.5 mMol) triethylamine followed by 0.8 mL (5.3 mMol) 1-naphthoyl chloride. After 18 hours the reaction mixture was partitioned between ethyl acetate and 1N sodium hydroxide. The phases were separated and the aqueous extracted again with ethyl acetate. The combined ethyl acetate extracts were then washed sequentially with 1N sodium hydroxide, water and saturated aqueous sodium chloride. The remaining organics were dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to flash chromatography, eluting with 100:10:1 dichloromethane:methanol:ammonium hydroxide. Fractions shown to contain product were combined and concentrated under reduced pressure. The residue was taken up in ethanol and treated with ethanolic hydrogen chloride. The solution was concentrated under reduced pressure and the residue crystallized from ethylacetate/ethanol to give 1.28 gm (58.2%) of the title compound as a tan powder.

Workup

  1. filtrationAfter 18 hours the reaction mixture was filtered
  2. dissolutionThe recovered filtrate was dissolved in 10 mL dimethylformamide to which
  3. customAfter 18 hours the reaction mixture was partitioned between ethyl acetate and 1N sodium hydroxide
  4. customThe phases were separated
  5. extractionthe aqueous extracted again with ethyl acetate
  6. washThe combined ethyl acetate extracts were then washed sequentially with 1N sodium hydroxide, water and saturated aqueous sodium chloride
  7. dry with materialThe remaining organics were dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. washeluting with 100:10:1 dichloromethane
  10. concentrationconcentrated under reduced pressure
  11. additiontreated with ethanolic hydrogen chloride
  12. concentrationThe solution was concentrated under reduced pressure
  13. customthe residue crystallized from ethylacetate/ethanol

Sources & evidence

ORD record
ord-c991eb115601477192127827d7062ba9
Source dataset
uspto-grants-1998_01
Patent number
US05708008

Reaction notes

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