Tris(1,1-dimethylethyl)phosphine → HCID 29923770, compound

HRID 1186294Notes

Reaction equation

HRID 1186294 reaction equation
C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.Br[C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][CH:19]=[C:18]2[CH2:24][CH2:25][N:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1.C[Si]([N-:35][Si](C)(C)C)(C)C.[Li+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:26]1([CH2:25][CH2:24][C:18]2[C:17]3[C:21](=[CH:22][CH:23]=[C:15]([NH2:35])[CH:16]=3)[NH:20][CH:19]=2)[CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

6

Reactant 3

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2733832Lithium HexamethyldisilazideHCID 158384855-bromo-3-(2-(pyrrolidin-1-yl)ethyl)-1H-indole

Product 1

HCID 29923770HCID 29923770, compoundYield 64.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of Pd2dba3 (0.187 g, 0.205 mmol) in dry THF (10 mL) was treated with tri-tert-butylphosphine (2.483 mL, 0.819 mmol) at room temperature. After stirring for 10 min., 5-bromo-3-(2-(pyrrolidin-1-yl)ethyl)-1H-indole (1.2 g, 4.09 mmol) in dry THF (10 mL) was added followed by lithium bis(trimethylsilyl)amide 1M THF (10.23 mL, 10.23 mmol) at same temperature. The reaction was placed in a pre-heated oil bath and stirred for 3.5 h at 100° C. in a sealed tube. The reaction was brought to room temperature, quenched with 1 N HCl solution (25 mL) and stirred for 30 min. The reaction was basified with 1 N NaOH solution (50 mL) and product was extracted into ethyl acetate (3×25 mL). The combined ethyl acetate layer was dried (Na2SO4) and solvent was evaporated to obtain crude product. The crude material was purified by column chromatography (2 M NH3 in MeOH:CH2Cl2, 5:95) to obtain 3-(2-(pyrrolidin-1-yl)ethyl)-1H-indol-5-amine (0.6 g, 2.62 mmol, 63.9% yield) as a brown foam. ESI-MS (m/z, %): 230 (MH+, 100).

Workup

  1. customThe reaction was placed in a pre-heated oil bath
  2. stirringstirred for 3.5 h at 100° C. in a sealed tube
  3. customwas brought to room temperature
  4. customquenched with 1 N HCl solution (25 mL)
  5. stirringstirred for 30 min
  6. extractionwas extracted into ethyl acetate (3×25 mL)
  7. dry with materialThe combined ethyl acetate layer was dried (Na2SO4) and solvent
  8. customwas evaporated
  9. customto obtain crude product
  10. customThe crude material was purified by column chromatography (2 M NH3 in MeOH:CH2Cl2, 5:95)

Sources & evidence

ORD record
ord-164d8c41c2c7478b92c8e90c7cc4ab8f
Source dataset
uspto-grants-2014_03
Patent number
US08673909B2

Reaction notes

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