4-Methylmorpholine → [(N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl)amino](diphenyl)acetic acid

HRID 254032Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 254032
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]([OH:58])=O)=[O:53])=[CH:48][CH:47]=2)=[CH:26][CH:25]=1.CN1CCOCC1.[C:68]1([C:74]([C:79]2[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=2)([C:76]([OH:78])=[O:77])[NH2:75])[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=1.[BH4-].[Na+].C([O-])(=O)C.[NH4+]>CN(C=O)C.CO>[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:60]=[CH:59][C:49]([O:50][CH2:51][C:52]([NH:54][CH2:55][C:56]([NH:75][C:74]([C:79]3[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=3)([C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=3)[C:76]([OH:78])=[O:77])=[O:58])=[O:53])=[CH:48][CH:47]=2)=[CH:28][CH:29]=1

Komponenten

9

Edukt 6

HCID 79724-MethylmorpholineHCID 182892,2-DiphenylglycineHCID 517165Ammonium AcetateHCID 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 66843246[(N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl)amino](diphenyl)acetic acidAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
30 °C

Versuchsvorschrift

TBTU (0.016 g, 0.050 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 (0.020 g, 0.037 mmol) and NMM (0.012 ml, 0.109 mmol) in DMF (2 ml) at 30° C. After 30 min, 2,2-diphenylglycine (0.009 g, 0.037 mmol, 98%) was added and the mixture was stirred at 30° C. for 2.5 h. The reaction was quenched with water (0.2 ml) and the mixture was diluted with MeOH (2 ml). NaBH4 (0.020 g, 0.529 mmol) was added and the mixture was stirred for 10 min. Ammonium acetate buffer (0.1M, 3 ml) was added and most of the methanol was removed under reduced pressure. The remaining solution was purified by preparative HPLC, using a gradient of 20-50% MeCN in 0.1M ammonium acetate buffer as eluent. After freeze-drying, the title compound (0.012 g, 44% yield) was obtained as a white solid. M/z: 752.0. 1H NMR (DMSO, 400 MHz): δ 2.83-2.95 (m, 2H), 3.75 (d, 2H), 4.24-4.28 (m, 1H), 4.54 (s, 1H), 4.68-4.75 (m, 1H), 5.02-5.06 (m, 1H), 6.95-7.03 (m, 2H), 7.04-7.38 (m, 20H), 8.43-8.51 (m, 1H), 8.90 (s, 1H).

Aufarbeitung

  1. customThe reaction was quenched with water (0.2 ml)
  2. additionthe mixture was diluted with MeOH (2 ml)
  3. stirringthe mixture was stirred for 10 min
  4. customwas removed under reduced pressure
  5. customThe remaining solution was purified by preparative HPLC
  6. customAfter freeze-drying

Quellen und Nachweise

ORD-Eintrag
ord-42bf2d7979af4bc4867bf579fbd26f0e
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07871998B2

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