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

HRID 504580Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 504580
[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](O)=[O:28])([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.[CH3:52][O:53][CH2:54][CH2:55][S:56]([NH2:59])(=[O:58])=[O:57].[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([C@@H: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:59][S:56]([CH2:55][CH2:54][O:53][CH3:52])(=[O:58])=[O:57])=[O:28])[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

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 189515062-Methoxyethane-1-sulfonamideHCID 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

Produkt 1

HCID 57750106(2'S,3S,4'R)-6-chloro-4'-{5-chloro-2-[2-(2-methoxy-ethanesulfonylamino)-1,1-dimethyl-2-oxo-ethoxy]-phenyl}-2'-(5-fluoro-2-methyl-phenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneAusbeute 16 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

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 (50 mg, 0.09 mmol) prepared in Example 12a and CDI (32 mg, 0.2 mmol) in DMF (2 mL) was heated at 60° C. for 2 h. Then to this solution was added a mixture of 2-methoxy-ethanesulfonic acid amide (139 mg, 1 mmol) and NaH (35 mg, 60%, 0.9 mmol) in DMF (2 mL), which had been stirred at room temperature for 3 h. 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 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).

Aufarbeitung

  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 phases were dried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customthe residue was purified by flash column

Quellen und Nachweise

ORD-Eintrag
ord-2157c99d68124eae8de5f84bc087e58f
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07776875B2

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