4-Methylmorpholine → n-{[4-((2r,3r)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-d-tryptophan

HRID 254045

Reaktionsgleichung

Reaktionsgleichung von HRID 254045
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[F:23][C:24]1[CH:29]=[CH:28][C:27]([N:30]2[C:33](=[O:34])[C@H:32]([S:35][CH2:36][C:37]([C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=3)=[O:38])[C@H:31]2[C:46]2[CH:60]=[CH:59][C:49]([O:50][CH2:51][C:52]([NH:54][CH2:55][C:56](O)=[O:57])=[O:53])=[CH:48][CH:47]=2)=[CH:26][CH:25]=1.CN1CCOCC1.[NH2:68][C@@H:69]([C:80]([OH:82])=[O:81])[CH2:70][C:71]1[C:79]2[C:74](=[CH:75][CH:76]=[CH:77][CH:78]=2)[NH:73][CH:72]=1.[BH4-].[Na+]>CN(C=O)C.CO.CS(C)=O>[F:23][C:24]1[CH:25]=[CH:26][C:27]([N:30]2[C:33](=[O:34])[C@H:32]([S:35][CH2:36][CH:37]([C:39]3[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=3)[OH:38])[C@H:31]2[C:46]2[CH:47]=[CH:48][C:49]([O:50][CH2:51][C:52]([NH:54][CH2:55][C:56]([NH:68][C@@H:69]([C:80]([OH:82])=[O:81])[CH2:70][C:71]3[C:79]4[C:74](=[CH:75][CH:76]=[CH:77][CH:78]=4)[NH:73][CH:72]=3)=[O:57])=[O:53])=[CH:59][CH:60]=2)=[CH:28][CH:29]=1

Komponenten

9

Edukt 5

HCID 79724-MethylmorpholineHCID 9060D-TryptophanHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 4311764Sodium borohydrideHCID 66842760N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio)-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine

Produkt 1

HCID 66842697n-{[4-((2r,3r)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-d-tryptophan

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittelHCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

TBTU (0.016 g, 0.051 mmol) was added to a solution of N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine (0.025 g, 0.046 mmol) and N-methylmorpholine (0.014 g, 0.139 mmol) in DMF (2 ml) at 30° C. After 1 h, DMSO (1 ml) and D-tryptophan (0.019 g, 0.092 mmol) were added. After 10 minutes, the reaction was quenched by the addition of water (1 ml). The mixture was stirred for 10 minutes and MeOH (1 ml) and NaBH4 (0.035 g, 0.925 mmol) were added. After 5 minutes, full conversion to the corresponding alcohol was obtained. The reaction was quenched by the addition of 0.1M NH4OAc buffer (1 ml). The reaction mixture was concentrated and the residue was purified by preparative HPLC using an eluent of 0-50% CH3CN in 0.1M NH4OAc buffer. This gave the title compound (0.028 g, 83%) as a colurless solid. M/z: 727.0 (M−1). 1H NMR [(CD3)2SO), 400 MHz] δ 2.79-3.18 (m, 4H), 3.61-3.80 (m, 2H), 4.26-4.34 (m, 2H), 4.43-4.54 (m, 2H), 4.68-4.78 (m, 1H), 4.97-5.04 (m, 1H), 6.84-7.55 (m, 1H), 7.65-7.82 (m, 1H), 8.22-8.25 (m, 1H), 10.73 (s, 1H).

Aufarbeitung

  1. waitAfter 10 minutes
  2. customthe reaction was quenched by the addition of water (1 ml)
  3. waitAfter 5 minutes

Quellen und Nachweise

ORD-Eintrag
ord-1e47365f563f4aaa8651be9737ea19dd
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07871998B2

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