Hydrochloric Acid → HCID 74928669, compound

HRID 504575Notes

Reaction equation

HRID 504575 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:40])[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](O)=[O:28])([CH3:26])[CH3:25])[CH2:14][C:13](=[O:30])[NH:12][CH:11]3[C:31]3[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][C:32]=3[O:38][CH3:39])[C:5]2=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:53][S:54]([NH2:57])(=[O:56])=[O:55].[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]([CH3:53])(=[O:56])=[O:55])=[O:28])=[C:16]([CH:15]2[CH2:14][C:13](=[O:30])[NH:12][CH:11]([C:31]3[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][C:32]=3[O:38][CH3:39])[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:40])[CH:21]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 86632094HCID 86632094, compound

Product 1

HCID 74928669HCID 74928669, compoundYield 10.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
65 °C

Procedure

A mixture of racemic (2′S,3S,4′R)-6-chloro-4′-[5-chloro-2-(1-hydroxycarbonyl-1-methyl-ethoxy)-phenyl]-2′-(5-methyl-2-methoxy-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (70 mg, 0.12 mmol) and CDI (39 mg, 0.24 mmol) in dry DMF (2 mL) was heated at 65° C. for 2 h. In a separate flask a mixture of methanesulfonamide (91 mg, 0.962 mmol) and NaH (60% in mineral oil) (38 mg, 0.95 mmol) (Aldrich) in DMF (3 mL), was stirred at room temperature for 2 h, then was added slowly to the above solution. The reaction mixture was stirred at room temperature for 2 h, then poured into water (3 mL) and the aqueous phase was acidified to “pH” 1-2 by addition of concentrated HCl. The mixture was extracted with EtOAc (20 mL) twice. The combined organic layers were dried over anhydrous Na2SO4, concentrated in vacuo and the residue was purified by Prep-HPLC to give the title compound as a white solid (8.5 mg).

Workup

  1. additionwas added slowly to the above solution
  2. stirringThe reaction mixture was stirred at room temperature for 2 h
  3. extractionThe mixture was extracted with EtOAc (20 mL) twice
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customthe residue was purified by Prep-HPLC

Sources & evidence

ORD record
ord-89dd6c48ccf94863814956748131566b
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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