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

HRID 504521
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 504521
[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]([F: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[CH3:38])[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:7]=[C:6]2[NH:8][C:9](=[O:39])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=4[O:23][C:24]([CH3:26])([CH3:25])[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[CH3:38])[C:5]2=[CH:4][CH:3]=1
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Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 765680086-chloro-4'-[5-fluoro-2-(1-hydroxycarbonyl-1-methyl-ethoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Produkt 1

HCID 74928462
6-chloro-4'-[5-fluoro-2-(2-methanesulfonylamino-1,1-dimethyl-2-oxo-ethoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione
Ausbeute 70,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

A solution of racemic (2′S,3S,4′R)-6-chloro-4′-[5-fluoro-2-(1-hydroxycarbonyl-1-methyl-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (100 mg, 0.18 mmol) and CDI (58 mg, 0.36 mmol) in DMF (5 mL) was heated at 60° C. for 0.5 h. 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 stirred at room temperature for 0.5 h, it was poured into water (5 mL) and the aqueous solution was acidified to “pH” 2-3 by concentrated aqueous hydrochloride. After 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 (80 mg).

Aufarbeitung

  1. additionThen to this solution was added
  2. stirringAfter the resulting mixture was stirred at room temperature for 0.5 h
  3. extractionAfter the 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

Quellen und Nachweise

ORD-Eintrag
ord-c53db75b1818444a8be30d8a84f5f2fc
Quelldatensatz
uspto-grants-2010_08
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07776875B2

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