Indole → (3'S)-1'-[4-(1H-indol-1-ylmethyl)benzoyl]-1,3'-bipyrrolidine

HRID 1163082Notes

Reaction equation

HRID 1163082 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].[N:12]1([CH:17]2[CH2:21][CH2:20][N:19]([C:22]([C:24]3[CH:29]=[CH:28][C:27]([CH2:30]Cl)=[CH:26][CH:25]=3)=[O:23])[CH2:18]2)[CH2:16][CH2:15][CH2:14][CH2:13]1>CN(C=O)C.C1COCC1>[N:1]1([CH2:30][C:27]2[CH:26]=[CH:25][C:24]([C:22]([N:19]3[CH2:20][CH2:21][C@H:17]([N:12]4[CH2:13][CH2:14][CH2:15][CH2:16]4)[CH2:18]3)=[O:23])=[CH:29][CH:28]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

5

Reactant 3

HCID 798IndoleHCID 24758Sodium hydrideHCID 63168064[1,3']Bipyrrolidinyl-1'-yl-(4-chloromethyl-phenyl)-methanone

Product 1

HCID 46230691(3'S)-1'-[4-(1H-indol-1-ylmethyl)benzoyl]-1,3'-bipyrrolidineYield 14.3%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

A solution of indole (0.15 mmol, 19 mg) in a mixture of DMF/THF (1:4, 2 mL) is treated with sodium hydride (50 mg) followed by [1,3′]bipyrrolidinyl-1′-yl-(4-chloromethyl-phenyl)-methanone (0.15 mmol, 43 mg), stirred at room temperature overnight and concentrated in vacuo. The resultant residue is dissolved in a mixture of DMSO, MeOH and water (1.5 mL) and purified by reverse-phase semi-preparative HPLC1 to give the title product as a white powder (8 mg), identified by HPLC and mass spectral analyses. Retention time 1.86 min., MS [374.2 m/e (M+H)].

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe resultant residue is dissolved in a mixture of DMSO, MeOH and water (1.5 mL)
  3. custompurified by reverse-phase semi-preparative HPLC1

Sources & evidence

ORD record
ord-ca644af6c273450a82124368cf440412
Source dataset
uspto-grants-2010_10
Patent number
US07820825B2

Reaction notes

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