Triethylamine → 1'-[(6-Chloro-1H-indol-3-yl)carbonyl]-2-methyl-2,3-dihydrospiro[isoindole-1,4'-piperidine]

HRID 2055555Notes

Reaction equation

HRID 2055555 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:13])=O)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.ClC(N(C)C)=C(C)C.[CH3:22][N:23]1[C:31]2([CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:24]1.C(N(CC)CC)C>ClCCl.CN(C)C=O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([N:34]3[CH2:35][CH2:36][C:31]4([C:30]5[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=5)[CH2:24][N:23]4[CH3:22])[CH2:32][CH2:33]3)=[O:13])=[CH:7][NH:8]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 184532356-chloro-1H-indole-3-carboxylic acidHCID 596575302-Methyl-2,3-dihydrospiro[isoindole-1,4'-piperidine]

Product 1

HCID 596576571'-[(6-Chloro-1H-indol-3-yl)carbonyl]-2-methyl-2,3-dihydrospiro[isoindole-1,4'-piperidine]Yield 29%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 0.040 g (0.20 mmol) 6-chloro-1H-indole-3-carboxylic acid in 3 ml dichloromethane were added 0.03 ml (0.22 mmol) 1-chloro-N,N,2-trimethyl-propenylamine at room temperature. After stirring for 1 h the reaction mixture was concentrated in vacuo. The residue was redissolved in 2 ml dry N,N-dimethylformamide. A solution of 0.041 g (0.20 mmol) 2-methyl-2,3-dihydrospiro[isoindole-1,4′-piperidine] and 0.043 ml (0.31 mmol) triethylamine in 1 ml dry N,N-dimethylformamide was added at room temperature. After stirring for 2 h the reaction mixture was quenched with 1 M aqueous sodium hydroxide solution (30 ml) and extracted with ethyl acetate (3×50 ml). The combined organic layers were washed with water (2×30 ml) and brine (1×30 ml), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (n-heptane/ethyl acetate) to give the title compound (0.022 g, 23%) as an off-white solid with a purity of approx. 83% by LC-MS.

Workup

  1. concentrationwas concentrated in vacuo
  2. dissolutionThe residue was redissolved in 2 ml dry N,N-dimethylformamide
  3. stirringAfter stirring for 2 h the reaction mixture
  4. customwas quenched with 1 M aqueous sodium hydroxide solution (30 ml)
  5. extractionextracted with ethyl acetate (3×50 ml)
  6. washThe combined organic layers were washed with water (2×30 ml) and brine (1×30 ml)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography (n-heptane/ethyl acetate)

Sources & evidence

ORD record
ord-7fbb27ebc28e4b68a136b0921f45f5cd
Source dataset
uspto-grants-2008_02
Patent number
US07332501B2

Reaction notes

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