Chlorotrimethylsilane → 3-((4-(2-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)-methoxy)acetyl)piperazin-1-yl)methyl)benzonitrile hydrochloride

HRID 2090807

Reaktionsgleichung

Reaktionsgleichung von HRID 2090807
COC1C=C(C)C(S(N2CCCCC2COCC(O)=O)(=O)=O)=C(C)C=1.N1(CC2C=C(C=CC=2)C#N)CCNCC1.C(=O)([O-])O.[Na+].[CH3:46][O:47][C:48]1[CH:53]=[C:52]([CH3:54])[C:51]([S:55]([N:58]2[CH2:63][CH2:62][CH2:61][CH2:60][CH:59]2[CH2:64][O:65][CH2:66][C:67]([N:69]2[CH2:74][CH2:73][N:72]([CH2:75][C:76]3[CH:77]=[C:78]([CH:81]=[CH:82][CH:83]=3)[C:79]#[N:80])[CH2:71][CH2:70]2)=[O:68])(=[O:57])=[O:56])=[C:50]([CH3:84])[CH:49]=1.[Cl:85][Si](C)(C)C>ClCCl.C(C(C)=O)C.C(OCC)C>[ClH:85].[CH3:46][O:47][C:48]1[CH:49]=[C:50]([CH3:84])[C:51]([S:55]([N:58]2[CH2:63][CH2:62][CH2:61][CH2:60][CH:59]2[CH2:64][O:65][CH2:66][C:67]([N:69]2[CH2:74][CH2:73][N:72]([CH2:75][C:76]3[CH:77]=[C:78]([CH:81]=[CH:82][CH:83]=3)[C:79]#[N:80])[CH2:71][CH2:70]2)=[O:68])(=[O:56])=[O:57])=[C:52]([CH3:54])[CH:53]=1

Komponenten

9

Edukt 5

HCID 6397ChlorotrimethylsilaneHCID 516892Sodium BicarbonateHCID 27579481-(3-Cyanobenzyl)piperazineHCID 249454933-((4-(2-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetyl)piperazin-1-yl)methyl)benzonitrileHCID 574368002-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid

Produkt 1

HCID 249454923-((4-(2-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)-methoxy)acetyl)piperazin-1-yl)methyl)benzonitrile hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3283Diethyl EtherLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 6569Methyl Ethyl KetoneLösungsmittel

Versuchsvorschrift

N,N′-Carbonyldiimidazole (68 mg, 0.424 mmol) was added to a solution of 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid (150 mg, 0.404 mmol) in dichloromethane (4 ml), and the mixture was stirred for 1 h at room temperature. A solution of 3-(piperazin-1-ylmethyl)benzonitrile (81 mg, 0.404 mmol) in dichloromethane (1 ml) was then added, and the reaction mixture was stirred for 15 h at room temperature. Saturated sodium hydrogen carbonate solution (5 ml) was then added to the reaction mixture, and then the aqueous phase was extracted with dichloromethane (2×10 ml). The combined organic phases were extracted with saturated sodium chloride solution (10 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography using ethyl acetate/hexane (20:1). 3-((4-(2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetyl)piperazin-1-yl)methyl)benzonitrile (100 mg, 0.180 mmol) was dissolved in methyl ethyl ketone (3 ml), and chlorotrimethylsilane (27 μl, 0.216 mmol) was added slowly. Diethyl ether (10 ml) was then added, and the mixture was stirred for 1 h at 0° C. The resulting precipitate was filtered off, dried with the exclusion of air and washed with diethyl ether.

Aufarbeitung

  1. stirringthe reaction mixture was stirred for 15 h at room temperature
  2. extractionthe aqueous phase was extracted with dichloromethane (2×10 ml)
  3. extractionThe combined organic phases were extracted with saturated sodium chloride solution (10 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography
  7. stirringthe mixture was stirred for 1 h at 0° C
  8. filtrationThe resulting precipitate was filtered off
  9. customdried with the exclusion of air
  10. washwashed with diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-95eb460f75884973865c78ad53cc2d84
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08435978B2

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