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

HRID 504591Notes

Reaction equation

HRID 504591 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]([OH:33])=O)([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]([F: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:33])([CH2:25][CH2:26][CH3:27])[CH2:28][CH2:29][CH3:30])[CH2:14][C:13](=[O:34])[NH:12][CH:11]3[C:35]3[CH:40]=[C:39]([F: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 722961896-chloro-4'-[5-chloro-2-(1-hydroxycarbonyl-1-propyl-butoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Product 1

HCID 749286916-chloro-4'-[5-chloro-2-(1-methanesulfonylaminocarbonyl-1-propyl-butoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 65.5%

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-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (80 mg, 0.13 mmol) and CDI (40 mg, 0.25 mmol) in DMF (2 mL) was heated at 60° C. for 2 h. Then to this solution was added a mixture of methanesulfonamide (123 mg, 1.3 mmol) and NaH (52 mg, 60%, 1.3 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 aqueous solution was acidified by 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 (60 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-fcab63dc82c24d6e8cf8a6e952e85573
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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