Diisopropylethylamine → 3-(Piperidin-4-yl)-1H-indole hydrochloride

HRID 1918655Notes

Reaction equation

HRID 1918655 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][CH2:13]N.CN(C(ON1N=NC2C=[CH:27][CH:28]=[N:29][C:24]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CO.C1COCC1.[OH-].[Na+].O.CN(C=O)C.C(OCC)(=O)C>[ClH:2].[NH:29]1[CH2:24][CH2:13][CH:12]([C:6]2[C:5]3[C:9](=[CH:10][CH:11]=[CH:3][CH:4]=3)[NH:8][CH:7]=2)[CH2:27][CH2:28]1

Participants

10

Reactant 3

HCID 81531DiisopropylethylamineHCID 28274945-Chloro-1H-indole-3-ethylamine monohydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 223805873-(Piperidin-4-yl)-1H-indole hydrochloride

Reagents, catalysts & solvents 6

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of an ethyl 5-substituted-1,2,4-oxadiazole-3-carboxylate (0.433 mmol, 1 equivalent) in methanol or THF (1 mL) and sodium hydroxide in water (2M, 5 equivalents) was stirred at room temperature until completion. The reaction mixture is the diluted with water and extracted with dichloromethane. The aqueous layer was acidified with HCl 6N until pH 2 and extracted with ethyl acetate. The combined organic extracts were dried over sodium sulphate and concentrated under reduced pressure. The residue was then added to a mixture of 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.433 mmol, 1 equivalent), HATU (0.432 mmol, 1 equivalent) and N,N diisopropylethylamine (0.433 mmol-1.08 mmol, 1-2.5 equivalents) in DMF (4 mL) and was stirred at room temperature overnight. The reaction mixture was diluted in ethyl acetate, washed with sodium disulphate, sodium carbonate and brine, dried and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica to yield the desired compounds.

Workup

  1. extractionextracted with dichloromethane
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic extracts were dried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. stirringwas stirred at room temperature overnight
  6. washwashed with sodium disulphate, sodium carbonate and brine
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by flash chromatography on silica

Sources & evidence

ORD record
ord-924e7673c111410b9cfa9f2e71033f00
Source dataset
uspto-grants-2013_12
Patent number
US08618138B2

Reaction notes

Loading…