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

HRID 504560Notes

Reaction equation

HRID 504560 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:41])[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]([CH2:30][CH3:31])([C:27](O)=[O:28])[CH2:25][CH3:26])[CH2:14][C:13](=[O:32])[NH:12][CH:11]3[C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[C:5]2=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:54][S:55]([NH2:58])(=[O:57])=[O:56].[H-].[Na+].Cl>CN(C=O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:41])[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]([CH2:25][CH3:26])([C:27]([NH:58][S:55]([CH3:54])(=[O:57])=[O:56])=[O:28])[CH2:30][CH3:31])[CH2:14][C:13](=[O:32])[NH:12][CH:11]3[C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[C:5]2=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 749285676-chloro-4'-[5-chloro-2-(1-ethyl-1-hydroxycarbonyl-propoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl) spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Product 1

HCID 749286006-chloro-4'-[5-chloro-2-(1-ethyl-1-methanesulfonylaminocarbonyl-propoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 29.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of racemic (2′S,3S,4′R)-6-chloro-4′-[5-chloro-2-(1-ethyl-1-hydroxycarbonyl-propoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (30 mg, 0.05 mmol) and CDI (20 mg, 0.12 mmol) in DMF (1 mL) was heated at 60° C. for 2 h. Then to this solution was added a mixture of methanesulfonamide (28 mg, 0.3 mmol) and NaH (12 mg, 60%, 0.3 mmol) in DMF (1 mL), which had been stirred for 2 h at room temperature. After the resulting mixture was stirred at room temperature for 1 h, it was poured into water and the aqueous solution was acidified to “PH” 1-2 by addition of concentrated HCl solution. The aqueous phase was extracted with EtOAc twice, The combined organic phases were dried over anhydrous Na2SO4, concentrated and the residue was purified by flash column to give the title compound as a white solid (10 mg).

Workup

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

Sources & evidence

ORD record
ord-f8cd78dde8954529a181f034ba385cc8
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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