Hydrochloric Acid → (2'S,3S,4'R)-4'-[5-chloro-2-(2-ethanesulfonylamino-1,1-dimethyl-2-oxo-ethoxy)-phenyl]-6-chloro-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 504572Notes

Reaction equation

HRID 504572 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:39])[C@@:10]3([C@@H:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][C:24]([C:27]([OH:29])=O)([CH3:26])[CH3:25])[CH2:14][C:13](=[O:30])[NH:12][C@H:11]3[C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[CH3:38])[C:5]2=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH2:52]([S:54]([NH2:57])(=[O:56])=[O:55])[CH3:53].[H-].[Na+].Cl>CN(C=O)C.O>[Cl:22][C:20]1[CH:19]=[CH:18][C:17]([O:23][C:24]([CH3:25])([CH3:26])[C:27]([NH:57][S:54]([CH2:52][CH3:53])(=[O:56])=[O:55])=[O:29])=[C:16]([C@H:15]2[CH2:14][C:13](=[O:30])[NH:12][C@@H:11]([C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[CH3:38])[C@:10]32[C:5]2[C:6](=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[NH:8][C:9]3=[O:39])[CH:21]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 73702EthanesulfonamideHCID 57566020(2'S,3S,4'R)-6-chloro-4'-[5-chloro-2-(1-hydroxycarbonyl-1-methyl-ethoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl) spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Product 1

HCID 57750130(2'S,3S,4'R)-4'-[5-chloro-2-(2-ethanesulfonylamino-1,1-dimethyl-2-oxo-ethoxy)-phenyl]-6-chloro-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 15.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of chiral (2′S,3S,4′R)-6-chloro-4′-[5-chloro-2-(1-hydroxycarbonyl-1-methyl-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (57 mg, 0.1 mmol) prepared in Example 12a and CDI (32 mg, 0.2 mmol) in DMF (1 mL) was heated at 60° C. for 2 h. Then to this solution was added a mixture of ethanesulfonamide (66 mg, 0.6 mmol) and NaH (24 mg, 60%, 0.6 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. 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 (10 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-8656bec2e8374a3792d9e73ccbfe5e08
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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