Hydrochloric Acid → 6-chloro-4'-[5-chloro-2-(1-ethyl-1-methanesulfonylaminocarbonyl-propoxy)-phenyl]-2'-(5-chloro-2-methyl-phenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 658923Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 658923
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:41])[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:29]([OH:31])=O)([CH2:27][CH3:28])[CH2:25][CH3:26])[CH2:14][C:13](=[O:32])[NH:12][CH:11]3[C:33]3[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[C:5]2=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:54][S:55]([NH2:58])(=[O:57])=[O:56].[H-].[Na+].Cl>CN(C=O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:41])[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]([CH2:27][CH3:28])([C:29]([NH:58][S:55]([CH3:54])(=[O:57])=[O:56])=[O:31])[CH2:25][CH3:26])[CH2:14][C:13](=[O:32])[NH:12][CH:11]3[C:33]3[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[C:5]2=[CH:4][CH:3]=1

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 722961836-chloro-4'-[5-chloro-2-(1-ethyl-1-hydroxycarbonyl-propoxy)-phenyl]-2'-(5-chloro-2-methyl-phenyl) spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Produkt 1

HCID 749286676-chloro-4'-[5-chloro-2-(1-ethyl-1-methanesulfonylaminocarbonyl-propoxy)-phenyl]-2'-(5-chloro-2-methyl-phenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneAusbeute 5,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

A solution of racemic (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(1-hydroxycarbonyl-1-ethyl-propoxy)-phenyl]-2′-(5-chloro-2-methyl-phenyl) spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (150 mg, 0.244 mmol) and CDI (80 mg, 0.49 mmol) in DMF (2 mL) was heated at 60° C. for 2 h. Then to this solution was added a mixture of methanesulfonamide (231 mg, 2.44 mmol) and NaH (78 mg, 60%, 1.95 mmol) in DMF (3 mL), which had been stirred at room temperature for 2 h. After stirred at room temperature for 1 h, the reaction mixture was poured into water and acidified to “pH” 2-3 by addition of aqueous concentrated HCl solution. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate twice. The combined organic extracts were dried over anhydrous Na2SO4, concentrated and the residue was purified by flash column chromatography to give the title compound as a white solid (10 mg).

Aufarbeitung

  1. additionThen to this solution was added
  2. stirringAfter stirred at room temperature for 1 h
  3. customThe mixture was partitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate twice
  6. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customthe residue was purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-0b909a369db74adab667cc1621cddd13
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08076482B2

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