1,2-Dichloroethane → 4-(4-((R)-(tert-butyldimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)-N-(4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide

HRID 1771212Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1771212
[Si:1]([O:8][C@@H:9]([C:25]1[CH:30]=[C:29](Cl)[CH:28]=[CH:27][C:26]=1[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:24]=[CH:23][C:19]([C:20]([OH:22])=O)=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:38]([N:40]([CH2:43][C@@H:44]1[N:49]([CH2:50][CH2:51][C@@H:52]([NH:61][C:62]2[CH:67]=[CH:66][C:65]([S:68]([NH2:71])(=[O:70])=[O:69])=[CH:64][C:63]=2[S:72]([C:75]([F:78])([F:77])[F:76])(=[O:74])=[O:73])[CH2:53][S:54][C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[CH2:48][CH2:47][O:46][CH2:45]1)[CH2:41][CH3:42])[CH3:39].C(Cl)C[Cl:81]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Si:1]([O:8][C@@H:9]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:32]1[CH:33]=[CH:34][C:35]([Cl:81])=[CH:36][CH:37]=1)[CH:10]1[CH2:11][CH2:12][N:13]([C:16]2[CH:17]=[CH:18][C:19]([C:20]([NH:71][S:68]([C:65]3[CH:66]=[CH:67][C:62]([NH:61][C@H:52]([CH2:51][CH2:50][N:49]4[CH2:48][CH2:47][O:46][CH2:45][C@@H:44]4[CH2:43][N:40]([CH2:41][CH3:42])[CH2:38][CH3:39])[CH2:53][S:54][C:55]4[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=4)=[C:63]([S:72]([C:75]([F:76])([F:78])[F:77])(=[O:74])=[O:73])[CH:64]=3)(=[O:69])=[O:70])=[O:22])=[CH:23][CH:24]=2)[CH2:14][CH2:15]1)([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:3])[CH3:2]

Komponenten

6

Edukt 3

HCID 111,2-DichloroethaneHCID 667234924-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2×HCID 66723720(R)-4-(4-((tert-butyldimethylsilyloxy)(4-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoic acid2×

Produkt 1

HCID 866618974-(4-((R)-(tert-butyldimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)-N-(4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamideAusbeute 43,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A solution of (R)-4-(4-((tert-butyldimethylsilyloxy)(4′-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoic acid, (INTERMEDIATE 13, 109 mg, 0.20 mmol), 4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 88, 130 mg, 0.20 mmol), EDC (78 mg, 0.41 mmol), DMAP (49.7 mg, 0.41 mmol), TEA (0.028 ml, 0.20 mmol) and DCM (5 ml) was stirred overnight at room temperature. The reaction mixture was diluted with DCM (50 ml) and washed successively with water (2×50 ml) and brine (50 ml). The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography (ISCO, eluting with 0-20 MeOH/DCM over 19 minutes) to give the title product (100 mg, yield: 42.5%).

Aufarbeitung

  1. washwashed successively with water (2×50 ml) and brine (50 ml)
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe concentrate was purified by column chromatography (ISCO, eluting with 0-20 MeOH/DCM over 19 minutes)

Quellen und Nachweise

ORD-Eintrag
ord-7737b1800bac4feca27bdafaeecce193
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09248140B2

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