Sodium hydride → 1'-({6-Chloro-1-[(3S)-piperidin-3-ylmethyl]-1H-indol-3-yl}carbonyl)-3H-spiro[2-benzofuran-1,4'-piperidine]

HRID 2055538Notes

Reaction equation

HRID 2055538 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([N:13]3[CH2:18][CH2:17][C:16]4([C:22]5[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=5[CH2:20][O:19]4)[CH2:15][CH2:14]3)=[O:12])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].C(OC([N:36]1[CH2:41][CH2:40][CH2:39][C@H:38]([CH2:42]OS(C)(=O)=O)[CH2:37]1)=O)(C)(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([N:13]3[CH2:18][CH2:17][C:16]4([C:22]5[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=5[CH2:20][O:19]4)[CH2:15][CH2:14]3)=[O:12])=[CH:7][N:8]2[CH2:42][C@H:38]2[CH2:39][CH2:40][CH2:41][NH:36][CH2:37]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10469651(S)-[[(Methylsulfonyl)oxy]methyl]piperidine-1-carboxylic Acid tert-Butyl EsterHCID 15951937(6-chloro-1H-indol-3-yl)-spiro[1H-2-benzofuran-3,4'-piperidine]-1'-ylmethanone

Product 1

HCID 596575381'-({6-Chloro-1-[(3S)-piperidin-3-ylmethyl]-1H-indol-3-yl}carbonyl)-3H-spiro[2-benzofuran-1,4'-piperidine]Yield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of the 1′-[(6-chloro-1H-indol-3-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine] (prepared according to example 69) in dry DMF was treated with NaH (1.1 eq) and stirred for 10 min at room temperature, then treated with (S)-3-methanesulfonyloxymethyl-piperidine-1-carboxylic acid tert-butyl ester (1.1 eq) (JP 2001278872) and stirred at room temperature for 16 h then 70° for 4 h. Concentration and treatment with excess HCl in dioxane gave after purification by preparative HPLC the desired product in 39% yield.

Workup

  1. stirringstirred at room temperature for 16 h
  2. wait70° for 4 h
  3. concentrationConcentration and treatment with excess HCl in dioxane
  4. customgave
  5. customafter purification by preparative HPLC the desired product in 39% yield

Sources & evidence

ORD record
ord-9567b863442b470bbab12017bd9db9cf
Source dataset
uspto-grants-2008_02
Patent number
US07332501B2

Reaction notes

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