Tris(dimethylamino)sulfonium difluorotrimethylsilicate → 4-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)-N-(4-((R)-4-(ethyl(2-hydroxyethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide

HRID 1771239Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1771239
CN([S+](N(C)C)N(C)C)C.C[Si-](F)(F)(C)C.[Si]([O:34][CH2:35][CH2:36][N:37]([CH2:102][CH3:103])[CH2:38][CH2:39][C@@H:40]([NH:49][C:50]1[CH:55]=[CH:54][C:53]([S:56]([NH:59][C:60](=[O:94])[C:61]2[CH:66]=[CH:65][C:64]([N:67]3[CH2:72][CH2:71][CH:70]([C@H:73]([C:81]4[CH:86]=[CH:85][CH:84]=[CH:83][C:82]=4[C:87]4[CH:92]=[CH:91][C:90]([Cl:93])=[CH:89][CH:88]=4)[NH:74][S@:75]([C:77]([CH3:80])([CH3:79])[CH3:78])=[O:76])[CH2:69][CH2:68]3)=[CH:63][CH:62]=2)(=[O:58])=[O:57])=[CH:52][C:51]=1[S:95]([C:98]([F:101])([F:100])[F:99])(=[O:97])=[O:96])[CH2:41][S:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C>[Cl:93][C:90]1[CH:91]=[CH:92][C:87]([C:82]2[CH:83]=[CH:84][CH:85]=[CH:86][C:81]=2[C@H:73]([NH:74][S@:75]([C:77]([CH3:78])([CH3:80])[CH3:79])=[O:76])[CH:70]2[CH2:71][CH2:72][N:67]([C:64]3[CH:65]=[CH:66][C:61]([C:60]([NH:59][S:56]([C:53]4[CH:54]=[CH:55][C:50]([NH:49][C@H:40]([CH2:39][CH2:38][N:37]([CH2:102][CH3:103])[CH2:36][CH2:35][OH:34])[CH2:41][S:42][C:43]5[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=5)=[C:51]([S:95]([C:98]([F:101])([F:100])[F:99])(=[O:96])=[O:97])[CH:52]=4)(=[O:58])=[O:57])=[O:94])=[CH:62][CH:63]=3)[CH2:68][CH2:69]2)=[CH:88][CH:89]=1

Komponenten

4

Edukt 2

HCID 9795567Tris(dimethylamino)sulfonium difluorotrimethylsilicateHCID 86661889N-(4-((R)-4-((2-(tert-butyldiphenylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)-4-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzamide

Produkt 1

HCID 866618904-(4-((R)-(4'-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)-N-(4-((R)-4-(ethyl(2-hydroxyethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamideAusbeute 114,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of TASF (0.46 ml. 0.46 mmol, 1 M in DMF) was added to a solution of N-(4-((R)-4-((2-(tert-butyldiphenylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)-4-(4-((R)-(4′-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzamide (EXAMPLE 12, STEP 1, 0.30 g, 0.23 mmol) in DMF (1.9 ml) and the reaction mixture was stirred at r.t for 1 hour. The reaction mixture was concentrated under reduced pressure, diluted with DCM and washed with H2O. The organic layer was dried (Na2SO4), concentrated under reduced pressure and dried under vacuum to give 4-(4-((R)-(4′-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)-N-(4-((R)-4-(ethyl(2-hydroxyethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide (EXAMPLE 12, STEP 2, 0.28 g) which was used in the preparation of EXAMPLE 12, STEP 3, without further purification.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with DCM
  3. washwashed with H2O
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-9cb760b8c9d34a4da0976652b2685f8d
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09248140B2

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