Hydrochloric Acid → 6-chloro-4'-[5-chloro-2-(1-methanesulfonylaminocarbonyl-1-propyl-butoxy)-phenyl]-2'-(5-chloro-2-methyl-phenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 504588Notes

Reaction equation

HRID 504588 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:43])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][C:24]([C:31](O)=[O:32])([CH2:28][CH2:29][CH3:30])[CH2:25][CH2:26][CH3:27])[CH2:14][C:13](=[O:34])[NH:12][CH:11]3[C:35]3[CH:40]=[C:39]([Cl:41])[CH:38]=[CH:37][C:36]=3[CH3:42])[C:5]2=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:56][S:57]([NH2:60])(=[O:59])=[O:58].[H-].[Na+].Cl>CN(C=O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:43])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][C:24]([C:31]([NH:60][S:57]([CH3:56])(=[O:59])=[O:58])=[O:32])([CH2:28][CH2:29][CH3:30])[CH2:25][CH2:26][CH3:27])[CH2:14][C:13](=[O:34])[NH:12][CH:11]3[C:35]3[CH:40]=[C:39]([Cl:41])[CH:38]=[CH:37][C:36]=3[CH3:42])[C:5]2=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 866321006-chloro-4'-[5-chloro-2-(1-hydroxycarbonyl-1-propyl-butoxy)-phenyl]-2'-(5-chloro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Product 1

HCID 749286906-chloro-4'-[5-chloro-2-(1-methanesulfonylaminocarbonyl-1-propyl-butoxy)-phenyl]-2'-(5-chloro-2-methyl-phenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of racemic (2′S,3S,4′R)-6-chloro-4′-[5-chloro-2-(1-hydroxycarbonyl-1-propyl-butoxy)-phenyl]-2′-(5-chloro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (140 mg, 0.22 mmol) and CDI (70 mg, 0.44 mmol) in DMF (2 mL) was heated at 60° C. for 2 h. Then to this solution was added a mixture of methanesulfonamide (207 mg, 2.2 mmol) and NaH (78 mg, 60%, 2 mmol) in DMF (2 mL), which had been stirred at room temperature for 2 h. After the resulting mixture was stirred at room temperature for 1 h, it was poured into water and the mixture was acidified to “pH” 1-2 by addition of concentrated HCl solution. After the aqueous phase was extracted with EtOAc twice, the combined organic layers were dried over anhydrous Na2SO4, concentrated and the residue was purified by flash column to give the title compound as a white solid (100 mg).

Workup

  1. additionThen to this solution was added
  2. stirringAfter the resulting mixture was stirred at room temperature for 1 h
  3. extractionAfter the aqueous phase was extracted with EtOAc twice
  4. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customthe residue was purified by flash column

Sources & evidence

ORD record
ord-8c2727e4e1d7447abfe3fc35dc6fc12e
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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