Hydrochloric Acid → HCID 74928773, compound

HRID 504513Notes

Reaction equation

HRID 504513 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:39])[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:27]([OH:29])=O)([CH3:26])[CH3:25])[CH2:14][C:13](=[O:30])[NH:12][CH:11]3[C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[Cl:38])[C:5]2=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:52][S:53]([NH2:56])(=[O:55])=[O:54].[H-].[Na+].Cl>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:8][C:9](=[O:39])[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]([CH3:25])([CH3:26])[C:27]([NH:56][S:53]([CH3:52])(=[O:55])=[O:54])=[O:29])[CH2:14][C:13](=[O:30])[NH:12][CH:11]3[C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[Cl:38])[C:5]2=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 131728296HCID 131728296, compound

Product 1

HCID 74928773HCID 74928773, compoundYield 62.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of racemic (2′R,3S,4′R)-6-chloro-2′-(2-chloro-5-fluoro-phenyl)-4′-[5-chloro-2-(1-hydroxycarbonyl-1-methyl-ethoxy)-phenyl]spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (143 mg, 0.24 mmol) and CDI (78 mg, 0.48 mmol) in DMF (5 mL) was stirred at room temperature for 30 min. Then to this solution was added a mixture of methanesulfonamide (475 mg, 5 mmol) and NaH (200 mg, 60%, 5 mmol) in DMF (5 mL), which had been stirred for 1 h at room temperature. After the resulting mixture was heated at 60° C. for 1 h, it was poured into water (5 mL) and the mixture was acidified by concentrated aqueous HCl, extracted with EtOAc twice. The combined extracts 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. temperatureAfter the resulting mixture was heated at 60° C. for 1 h
  3. extractionextracted with EtOAc twice
  4. dry with materialThe combined extracts were dried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customthe residue was purified by flash column

Sources & evidence

ORD record
ord-0dd653bc4f974fa79cbfcbb3eeda47c3
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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